98 results on '"Famiglietti, V."'
Search Results
2. Three dimensional primary cultures for selecting human breast cancers that are sensitive to the anti-tumor activity of ipatasertib or taselisib in combination with anti-microtubule cytotoxic drugs
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Orditura, M., Della Corte, C.M., Diana, A., Ciaramella, V., Franzese, E., Famiglietti, V., Panarese, I., Franco, R., Grimaldi, A., Lombardi, A., Caraglia, M., Santoriello, A., Procaccini, E., Lieto, E., Maiello, E., De Vita, F., Ciardiello, F., and Morgillo, F.
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- 2018
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3. Cetuximab as third-line rechallenge plus either irinotecan or avelumab is an effective treatment in metastatic colorectal cancer patients with baseline plasma RAS/BRAF wild-type circulating tumor DNA: Individual patient data pooled analysis of CRICKET and CAVE trials
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Martini, G, Ciardiello, D, Famiglietti, V, Rossini, D, Antoniotti, C, Troiani, T, Napolitano, S, Esposito, L, Latiano, T P, Maiello, E, Del Re, M, Lonardi, S, Aprile, G, Santini, D, Masi, G, Avallone, A, Normanno, N, Pietrantonio, F, Pinto, C, Ciardiello, F, Cremolini, C, Martinelli, E, Martini, G, Ciardiello, D, Famiglietti, V, Rossini, D, Antoniotti, C, Troiani, T, Napolitano, S, Esposito, L, Latiano, T P, Maiello, E, Del Re, M, Lonardi, S, Aprile, G, Santini, D, Masi, G, Avallone, A, Normanno, N, Pietrantonio, F, Pinto, C, Ciardiello, F, Cremolini, C, and Martinelli, E
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metastatic colorectal cancer ,cetuximab ,rechallenge ,immunotherapy - Abstract
The rechallenge strategy is based on the concept that a subset of patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) could still benefit of epidermal growth factor receptor (EGFR) inhibition, after progression to an anti-EGFR based-therapy. We performed a pooled analysis of two-phase II prospective trials to determine the role of rechallenge in third-line mCRC patients with RAS/BRAF WT baseline circulating tumor DNA (ctDNA). Individual data of 33 and 13 patients from CAVE and CRICKET trials that received as third-line therapy cetuximab rechallenge were collected. Overall survival (OS), Progression-free survival (PFS), Overall response rate (ORR), Stable disease (SD) > 6 months were calculated. Adverse events were reported. For the whole 46 patient population, median PFS (mPFS) was 3.9 months (95% Confidence Interval, CI 3.0-4.9) with median OS (mOS) of 16.9 months (95% CI 11.7-22.1). For CRICKET patients, mPFS was 3.9 months (95% CI 1.7-6.2); mOS was 13.1 months (95% CI 7.3-18.9) with OS rates at 12, 18, and 24 months of 62%, 23%, and 0%, respectively. For CAVE patients, mPFS was 4.1 months (95% CI 3.0-5.2); mOS was 18.6 months (95% CI 11.7-25.4) with OS rates at 12, 18, 24 months of 61%, 52%, 21%, respectively. Skin rash was more frequently reported in CAVE trial (87.9% vs. 30.8%; p = 0.001), whereas a increased incidence of hematological toxicities was observed in CRICKET trial (53.8%% vs. 12.1%; p = 0.003). Third-line cetuximab rechallenge in combination with either irinotecan or avelumab in RAS/BRAF WT ctDNA mCRC patients represents a promising therapy.
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- 2023
4. Cetuximab as third‐line rechallenge plus either irinotecan or avelumab is an effective treatment in metastatic colorectal cancer patients with baseline plasma RAS/BRAF wild‐type circulating tumor DNA : Individual patient data pooled analysis of CRICKET and CAVE trials
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Martini, G., primary, Ciardiello, D., additional, Famiglietti, V., additional, Rossini, D., additional, Antoniotti, C., additional, Troiani, T., additional, Napolitano, S., additional, Esposito, L., additional, Latiano, T. P., additional, Maiello, E., additional, Del Re, M., additional, Lonardi, S., additional, Aprile, G., additional, Santini, D., additional, Masi, G., additional, Avallone, A., additional, Normanno, N., additional, Pietrantonio, F., additional, Pinto, C., additional, Ciardiello, F., additional, Cremolini, C., additional, and Martinelli, E., additional
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- 2023
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5. Clinical efficacy of sequential treatments in KRASG12C-mutant metastatic colorectal cancer: findings from a real-life multicenter Italian study (CRC-KR GOIM)
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Ciardiello, D, Chiarazzo, C, Famiglietti, V, Damato, A, Pinto, C, Zampino, M G, Castellano, G, Gervaso, L, Zaniboni, A, Oneda, E, Rapisardi, S, Bordonaro, R, Zichi, C, De Vita, F, Di Maio, M, Parisi, A, Giampieri, R, Berardi, R, Lavacchi, D, Antonuzzo, L, Tamburini, E, Maiorano, B A, Parrella, P, Latiano, T P, Normanno, N, De Stefano, A, Avallone, A, Martini, G, Napolitano, S, Troiani, T, Martinelli, E, Ciardiello, F, Maiello, E, Ciardiello, D, Chiarazzo, C, Famiglietti, V, Damato, A, Pinto, C, Zampino, M G, Castellano, G, Gervaso, L, Zaniboni, A, Oneda, E, Rapisardi, S, Bordonaro, R, Zichi, C, De Vita, F, Di Maio, M, Parisi, A, Giampieri, R, Berardi, R, Lavacchi, D, Antonuzzo, L, Tamburini, E, Maiorano, B A, Parrella, P, Latiano, T P, Normanno, N, De Stefano, A, Avallone, A, Martini, G, Napolitano, S, Troiani, T, Martinelli, E, Ciardiello, F, and Maiello, E
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KRASG12C mutation ,Cancer Research ,real-world data ,Irinotecan ,chemotherapy ,first line treatment ,Oxaliplatin ,Treatment Outcome ,Oncology ,mCRC ,Antineoplastic Combined Chemotherapy Protocols ,Colonic Neoplasms ,Humans ,Fluorouracil ,Colorectal Neoplasms ,Retrospective Studies - Abstract
Background: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units. Patients and methods: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out. Results: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months). Conclusion: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients.
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- 2022
6. O-7 Evidence of therapeutic effectiveness of third-line cetuximab rechallenge in appropriately selected patients: Findings from long-term follow-up of CRICKET and CAVE trials
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Martinelli, E., primary, Martini, G., additional, Ciardiello, D., additional, Famiglietti, V., additional, Rossini, D., additional, Antoniotti, C., additional, Troiani, T., additional, Napolitano, S., additional, Esposito, L., additional, Latiano, T., additional, Maiello, E., additional, Del Re, M., additional, Lonardi, S., additional, Aprile, G., additional, Santini, D., additional, Masi, G., additional, Avallone, A., additional, Normanno, N., additional, Pietrantonio, F., additional, Pinto, C., additional, Ciardiello, F., additional, and Cremolini, C., additional
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- 2022
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7. 163P Anti-tumor activity of cetuximab plus avelumab in non-small cell lung cancer patients involves innate immunity activation: Findings from the CAVE-lung trial
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Della Corte, C.M., primary, Fasano, M., additional, Ciaramella, V., additional, Cimmino, F., additional, Cardnell, R., additional, Gay, C.M., additional, Ramkumar, K., additional, Diao, L., additional, Di Liello, R., additional, Viscardi, G., additional, Famiglietti, V., additional, Ciardiello, D., additional, Martini, G., additional, Napolitano, S., additional, Troiani, T., additional, Martinelli, E., additional, Wang, J., additional, Byers, L., additional, Morgillo, F., additional, and Ciardiello, F., additional
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- 2022
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8. P-199 Baseline neutrophil to lymphocyte ratio predicts survival in patients with metastatic colorectal cancer treated with cetuximab plus avelumab (CAVE) as a rechallenge strategy
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Ciardiello, D., primary, Famiglietti, V., additional, Napolitano, S., additional, Terminiello, M., additional, Borrelli, C., additional, Vitiello, P., additional, Pietrantonio, F., additional, Avallone, A., additional, Normanno, N., additional, Maiello, E., additional, Latiano, T., additional, Cremolini, C., additional, Santabarbara, G., additional, Pinto, C., additional, Santini, D., additional, Esposito, L., additional, Di Liello, A., additional, Troiani, T., additional, Ciardiello, F., additional, Martinelli, E., additional, and Martini, G., additional
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- 2021
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9. 620P A phase II trial evaluating the activity of cabozantinib in pre-treated patients with metastatic colorectal cancer (mCRC): ABACO trial initial molecular data
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Martini, G., Troiani, T., Ciardiello, D., Napolitano, S., Famiglietti, V., Arrichiello, G., Esposito, L., Franco, R., Zito Marino, F., Panarese, I., Cardone, C., Maiello, E., Latiano, T.P., Avallone, A., Vitiello, P.P., Mariella, E., Reginelli, A., Ciardiello, F., and Martinelli, E.
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- 2023
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10. 559MO Rechallenge with EGFR inhibitors in ctDNA RAS/BRAF wild type refractory metastatic colorectal cancer: Individual patients’ data pooled analysis from 4 phase II trials
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Ciardiello, D., Mauri, G., Rossini, D., Famiglietti, V., Martini, G., Napolitano, S., Del Tufo, S., Zampino, M.G., Avallone, A., Pietrantonio, F., Lonardi, S., Santini, D., Masi, G., Siena, S., Bardelli, A., Ciardiello, F., Cremolini, C., Sartore Bianchi, A., Troiani, T., and Martinelli, E.
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- 2023
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11. SO-24 Panitumumab plus trifluridine/tipiracil as anti-EGFR rechallenge therapy in patients with refractory RAS wild-type metastatic colorectal cancer: Overall survival and subgroup analysis of the randomized phase 2 VELO trial
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Ciardiello, D., Napolitano, S., De Falco, V., Martini, G., Martinelli, E., Della Corte, C., Esposito, L., Famiglietti, V., Di Liello, A., Avallone, A., Cardone, C., De Stefano, A., Montesarchio, V., Zampino, M., Fazio, N., Del Tufo, S., Di Maio, M., De Vita, F., Altucci, L., Marrone, F., Ciardiello, F., and Troiani, T.
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- 2023
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12. P-227 A phase II trial evaluating the Activity of caBozantinib in pre-treated pAtients with metastatic COlorectal cancer (mCRC): ABACO trial
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Martini, G., Troiani, T., Ciardiello, D., Napolitano, S., Famiglietti, V., Esposito, L., Arrichiello, G., De Falco, V., Cardone, C., Maiello, E., Latiano, T., Di Bisceglie, M., Varriale, E., Vitiello, P., Bardelli, A., Mariella, E., Avallone, A., Ciardiello, F., and Martinelli, E.
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- 2023
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13. 397O Avelumab plus cetuximab in pre-treated RAS wild type metastatic colorectal cancer patients as a rechallenge strategy: The phase II CAVE (cetuximab-avelumab) mCRC study
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Martinelli, E., primary, Martini, G., additional, Troiani, T., additional, Pietrantonio, F., additional, Avallone, A., additional, Normanno, N., additional, Nappi, A., additional, Maiello, E., additional, Falcone, A., additional, Santabarbara, G., additional, Pinto, C., additional, Santini, D., additional, Ciardiello, D., additional, Terminiello, M., additional, Borrelli, C., additional, Napolitano, S., additional, Renato, D., additional, Famiglietti, V., additional, Esposito, L., additional, and Ciardiello, F., additional
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- 2020
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14. 173P Prognostic impact of progesterone receptor levels in luminal-like Her2- early breast cancer patients: A retrospective analysis
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Carlino, F., primary, Diana, A., additional, Buono, G., additional, Arpino, G., additional, Franzese, E., additional, Oikonomidou, O., additional, Famiglietti, V., additional, Signoriello, G., additional, De Vita, F., additional, Ciardiello, F., additional, and Orditura, M., additional
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- 2020
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15. 1335P Anti-tumour efficacy of cetuximab plus avelumab in NSCLC through induction of ADCC: Final data from CAVE-lung trial
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Fasano, M., primary, Della Corte, C.M., additional, Di Liello, R., additional, Barra, G., additional, Cimmino, F., additional, Sparano, F., additional, Viscardi, G., additional, Iacovino, M.L., additional, Paragliola, F., additional, Famiglietti, V., additional, Ciaramella, V., additional, Sforza, V., additional, Morabito, A., additional, Maiello, E., additional, Ciardiello, F., additional, and Morgillo, F., additional
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- 2020
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16. P-190 A retrospective study of regorafenib versus trifluridine/tipiracil efficacy in chemorefractory metastatic colorectal cancer patients: Multi-institution real-life clinical data
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Vitale, P., primary, Zanaletti, N., additional, Lombardi, P., additional, Milanesio, M., additional, Falco, V. De, additional, Terminiello, M., additional, Giunta, E., additional, Vitiello, P., additional, Caputo, V., additional, Borrelli, C., additional, Arrichiello, G., additional, Poliero, L., additional, Ciardiello, D., additional, Napolitano, S., additional, Martini, G., additional, Martinelli, E., additional, Famiglietti, V., additional, Fenocchio, E., additional, Keränen, S. Roselló, additional, Cervantes, A., additional, Ciardiello, F., additional, and Troiani, T., additional
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- 2020
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17. Genomic profiling of non-oncogene-addicted aNSCLC using liquid biopsy. A single institution Italian experience
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Di Liello, R., primary, Viscardi, G., additional, Sparano, F., additional, Della Corte, C.M., additional, Iacovino, M.L., additional, Paragliola, F., additional, Famiglietti, V., additional, Di Liello, A., additional, Ciardiello, F., additional, and Morgillo, F., additional
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- 2019
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18. Clinical practice use of liquid biopsy to identify RAS/BRAF mutational status in patients with metastatic colorectal cancer: A single institution experience
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De Falco, V., primary, Vitiello, P., additional, Giunta, E., additional, Ciardiello, D., additional, Stefania, N., additional, Cardone, C., additional, Vitale, P., additional, Zanaletti, N., additional, Terminiello, M., additional, Poliero, L., additional, Borrelli, C., additional, Caputo, V., additional, Arrichiello, G., additional, Mattera Iacono, V., additional, Marrone, F., additional, Famiglietti, V., additional, Martinelli, E., additional, Ciardiello, F., additional, and Troiani, T., additional
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- 2019
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19. Retrospective study of Regorafenib versus Trifluridine/Tipiracil efficacy in chemorefractory metastatic colorectal cancer patients: a single Italian institution real-life clinical data
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Vitale, P., primary, Zanaletti, N., additional, Vitiello, P., additional, martinelli, e., additional, Ciardiello, D., additional, De Falco, V., additional, Giunta, E., additional, Poliero, L., additional, Terminiello, M., additional, Borrelli, C., additional, Caputo, V., additional, Arrichiello, G., additional, Martini, G., additional, Stefania, N., additional, Famiglietti, V., additional, Cardone, C., additional, Ciardiello, F., additional, and Troiani, T., additional
- Published
- 2019
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20. AXL has a prognostic role in metastatic colorectal cancer (mCRC) and is a predictive biomarker of lack of efficacy of chemotherapy (CT) + cetuximab in RAS wild type (WT) patients (pts)
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Cardone, C., primary, Blauensteiner, B., additional, Moreno-Viedma, V., additional, Paul, M.C., additional, Martini, G., additional, Vitiello, P.P., additional, Ciardiello, D., additional, Borrelli, C., additional, Poliero, L., additional, Vitale, P., additional, Zanaletti, N., additional, Famiglietti, V., additional, Rachiglio, A.M., additional, Rizzi, D., additional, Maiello, E., additional, Latiano, T.P., additional, Normanno, N., additional, Sibilia, M., additional, Ciardiello, F., additional, and Martinelli, E., additional
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- 2018
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21. 17P - Genomic profiling of non-oncogene-addicted aNSCLC using liquid biopsy. A single institution Italian experience
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Di Liello, R., Viscardi, G., Sparano, F., Della Corte, C.M., Iacovino, M.L., Paragliola, F., Famiglietti, V., Di Liello, A., Ciardiello, F., and Morgillo, F.
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- 2019
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22. P-330 - Retrospective study of Regorafenib versus Trifluridine/Tipiracil efficacy in chemorefractory metastatic colorectal cancer patients: a single Italian institution real-life clinical data
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Vitale, P., Zanaletti, N., Vitiello, P., martinelli, e., Ciardiello, D., De Falco, V., Giunta, E., Poliero, L., Terminiello, M., Borrelli, C., Caputo, V., Arrichiello, G., Martini, G., Stefania, N., Famiglietti, V., Cardone, C., Ciardiello, F., and Troiani, T.
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- 2019
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23. P-326 - Clinical practice use of liquid biopsy to identify RAS/BRAF mutational status in patients with metastatic colorectal cancer: A single institution experience
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De Falco, V., Vitiello, P., Giunta, E., Ciardiello, D., Stefania, N., Cardone, C., Vitale, P., Zanaletti, N., Terminiello, M., Poliero, L., Borrelli, C., Caputo, V., Arrichiello, G., Mattera Iacono, V., Marrone, F., Famiglietti, V., Martinelli, E., Ciardiello, F., and Troiani, T.
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- 2019
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24. LA SODDISFAZIONE DEGLI UTENTI NEI PRESIDI OSPEDALIERI DELLA ASL AV1
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FERRANTE NVF, MELITO P, FRANCIOSI G, FAMIGLIETTI V, GALDO V, ATTENA, Francesco, Ferrante, Nvf, Melito, P, Franciosi, G, Famiglietti, V, Galdo, V, and Attena, Francesco
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- 2009
25. 96P - AXL has a prognostic role in metastatic colorectal cancer (mCRC) and is a predictive biomarker of lack of efficacy of chemotherapy (CT) + cetuximab in RAS wild type (WT) patients (pts)
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Cardone, C., Blauensteiner, B., Moreno-Viedma, V., Paul, M.C., Martini, G., Vitiello, P.P., Ciardiello, D., Borrelli, C., Poliero, L., Vitale, P., Zanaletti, N., Famiglietti, V., Rachiglio, A.M., Rizzi, D., Maiello, E., Latiano, T.P., Normanno, N., Sibilia, M., Ciardiello, F., and Martinelli, E.
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- 2018
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26. Detoxification of chlorinated organic compounds using hydrodechlorination on sulphided NiO-MoO3/-Al2O3 catalyst. Kinetic analysis and effect of temperature
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MURENA, FABIO, GIOIA, FRANCESCO, Famiglietti V., Murena, Fabio, Famiglietti, V., and Gioia, Francesco
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rifiuti tossici ,cinetica ,idrodeclorazione - Published
- 1993
27. Effect of hydrogen pressure on detoxification of 1,2,3-trichlorobenzene by catalytic hydrodechlorination with both unsulphided and sulphided NiMoγ-Al2O3 catalyst
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Gioia, F., primary, Gallagher, E.J., additional, and Famiglietti, V., additional
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- 1994
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28. Catalytic hydrodechlorination of 1,2,3-trichlorobenzene
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Gioia, F., primary, Famiglietti, V., additional, and Murena, F., additional
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- 1993
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29. Biomarker-Guided Anti-Egfr Rechallenge Therapy in Metastatic Colorectal Cancer
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Stefania Napolitano, Vincenzo Famiglietti, Vincenzo De Falco, J. Ros, Elena Elez Fernandez, Pietro Paolo Vitiello, Fortunato Ciardiello, Evaristo Maiello, Tiziana Latiano, Teresa Troiani, Giulia Martini, Davide Ciardiello, Erika Martinelli, Institut Català de la Salut, [Ciardiello D] Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy. Oncologia Medica, Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy. [Martini G, Famiglietti V, Napolitano S, De Falco V, Troiani T] Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy. [Ros J] Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, 80131 Naples, Italy. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, 08035 Barcelona, Spain. [Elez Fernandez E] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, 08035 Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Ciardiello, D., Martini, G., Famiglietti, V., Napolitano, S., De Falco, V., Troiani, T., Latiano, T. P., Ros, J., Fernandez, E. E., Vitiello, P. P., Maiello, E., Ciardiello, F., and Martinelli, E.
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,rechallenge ,anti-EGFR monoclonal antibodies ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Review ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES] ,Growth factor receptor ,Metàstasi ,Anti-EGFR monoclonal antibodie ,Internal medicine ,Recte - Càncer - Tractament ,Medicine ,Panitumumab ,Còlon - Càncer -Tractament ,Other subheadings::/therapeutic use [Other subheadings] ,Liquid biopsy ,RC254-282 ,Chemotherapy ,Cetuximab ,business.industry ,Otros calificadores::/uso terapéutico [Otros calificadores] ,metastatic colorectal cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] ,medicine.disease ,neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES] ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,Biomarker (medicine) ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] ,business ,medicine.drug - Abstract
Simple Summary The survival of patients with metastatic colorectal cancer (mCRC) has been improved over the years and now reaches 30–40 months. However, few therapeutic options are available after failure of first- and second-line treatments. In fact, prognosis of chemo-refractory mCRC remains poor. Therefore, new therapeutic strategies are needed. Emerging evidence suggest that retreatment with epidermal growth factor (EGFR) inhibitors after a treatment break, in patients that obtained a clinical benefit by previous anti-EGFR, could lead to prolonged survival. The rationale beyond this “rechallenge” strategy is that after a “treatment holiday” EGFR resistant cancer cells decay, restoring the sensibility to EGFR blockade. In this review we analyze the current knowledge of retreatment with EGFR inhibitors, examine the role of novel biomarkers that can guide the appropriate selection of patients. Finally, we discuss future perspectives and on-going clinical trials. Abstract The prognosis of patients with metastatic colorectal cancer (mCRC) who progressed to the first and the second lines of treatment is poor. Thus, new therapeutic strategies are needed. During the last years, emerging evidence suggests that retreatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MAbs) in the third line of mCRC patients, that have previously obtained clinical benefit by first-line therapy with anti-EGFR MAbs plus chemotherapy, could lead to prolonged survival. The rationale beyond this “rechallenge” strategy is that, after disease progression to first line EGFR-based therapy, a treatment break from anti-EGFR drugs results in RAS mutant cancer cell decay, restoring the sensitivity of cancer cells to cetuximab and panitumumab. In fact, rechallenge treatment with anti-EGFR drugs has shown promising clinical activity, particularly in patients with plasma RAS and BRAF wild type circulating tumor DNA, as defined by liquid biopsy analysis at baseline treatment. The aim of this review is to analyze the current knowledge on rechallenge and to investigate the role of novel biomarkers that can guide the appropriate selection of patients that could benefit from this therapeutic strategy. Finally, we discuss on-going trials and future perspectives.
- Published
- 2021
30. Effect of hydrogen pressure on detoxification of 1,2,3-trichlorobenzene by catalytic hydrodechlorination with both unsulphided and sulphided [formula omitted] catalyst
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Gioia, F., Gallagher, E.J., and Famiglietti, V.
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- 1994
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31. Real-world clinical outcome and safety of adjuvant therapy in stage III melanoma patients: Data from two Academic Italian Institutions
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Vincenzo De Falco, Gabriella Suarato, Rossella Napolitano, Giuseppe Argenziano, Vincenzo Famiglietti, Annarita Amato, Alberto Servetto, Roberto Bianco, Luigi Formisano, Vincenzo Terrano, Alfonso Esposito, Maria Cristina Giugliano, Davide Ciardiello, Fortunato Ciardiello, Stefania Napolitano, Teresa Troiani, De Falco, V., Suarato, G., Napolitano, R., Argenziano, G., Famiglietti, V., Amato, A., Servetto, A., Bianco, R., Formisano, L., Terrano, V., Esposito, A., Giugliano, M. C., Ciardiello, D., Ciardiello, F., Napolitano, S., Troiani, T., De Falco, Vincenzo, Suarato, Gabriella, Napolitano, Rossella, Argenziano, Giuseppe, Famiglietti, Vincenzo, Amato, Annarita, Servetto, Alberto, Bianco, Roberto, Formisano, Luigi, Terrano, Vincenzo, Esposito, Alfonso, Giugliano, Maria Cristina, Ciardiello, Davide, Ciardiello, Fortunato, Napolitano, Stefania, and Troiani, Teresa
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Cancer Research ,Oncology ,real-world data ,melanoma ,adjuvant therapy ,immunotherapy ,targeted therapy - Abstract
Adjuvant immunotherapy (IO) and targeted therapy (TT) have improved relapse-free survival (RFS) in patients with stage III melanoma, although about 25% of them relapse within a year. However, real-world data on treatment efficacy and safety as well as management of treatment recurrences are still limited. We retrospectively analyzed 113 patients with stage III melanoma who received at least one cycle of anti-PD-1 (nivolumab or pembrolizumab) or dabrafenib + trametinib as adjuvant therapy. Most of patients included into the analyses harbor BRAV600E mutation (66.4%) and had a stage IIIC melanoma (63.7%). Immunotherapy was administered in 48.7% of patients, whereas targeted therapy in 51.3% At data cut-off, median RFS was not reached with 12- and 24-months RFS of 81% and 64%, respectively. No new adverse events were registered. Thirty patients (26.5%) relapsed, mainly at distant sites. Patient treated with IO recurred mostly during adjuvant treatment (ON-treatment) while patients treated with TT relapsed at the end of treatment (OFF-treatment). At relapse, surgery, radiotherapy and systemic therapy were used alone or in combination. Among patients who started a first-line therapy, an excellent response switching to a different treatment was observed. Real-world outcomes and safety of adjuvant treatment for resected stage III melanoma appear comparable to clinical trials data. Moreover, management of recurrences depends on type of relapse (loco-regional vs distant) and timing (during vs OFF treatment). Furthermore, patients who relapse after adjuvant TT respond well to subsequent anti-PD1 based therapy.
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- 2023
32. Prognostic Relevance of Progesterone Receptor Levels in Early Luminal-Like HER2 Negative Breast Cancer Subtypes: A Retrospective Analysis
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Diana, Anna, Carlino, Francesca, Buono, Giuseppe, Antoniol, Giuliano, Famiglietti, Vincenzo, De Angelis, Carmine, Carrano, Simone, Piccolo, Antonio, De Vita, Ferdinando, Ciardiello, Fortunato, Daniele, Bruno, Arpino, Grazia, Orditura, Michele, Diana, Anna, Carlino, Francesca, Buono, Giuseppe, Antoniol, Giuliano, Famiglietti, Vincenzo, De Angelis, Carmine, Carrano, Simone, Piccolo, Antonio, De Vita, Ferdinando, Ciardiello, Fortunato, Bruno, Daniele, Arpino, Grazia, Orditura, Michele, Diana, A, Carlino, F, Buono, G, Antoniol, G, Famiglietti, V, De Angelis, C, Carrano, S, Piccolo, A, De Vita, F, Ciardiello, F, Daniele, B, Arpino, G, and Orditura, M.
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Cancer Research ,breast cancer ,Oncology ,luminal-like subtype ,prognosis ,Ki67 ,progesterone receptor - Abstract
IntroductionIn luminal-like early breast cancer (BC), the lack of Progesterone Receptor (PR) expression generally correlates with more aggressive behavior but the clinical validity of low PR levels remains a debated issue.MethodsThe main aim of this retrospective analysis was to assess the survival outcome (Breast cancer specific survival, BCSS) in a cohort of 687 luminal-like HER2 negative early BC patients treated at our Institutions from January 2000 to December 2018, using a sub-classification of tumors in subgroup 1 (PR high/Ki67 low), subgroup 2 (PR high/Ki67 high), subgroup 3 (PR low/Ki67 low), subgroup 4 (PR low/Ki67 high) according to PR and Ki67 values.ResultsAt a median follow-up of 7 years, BCSS rates were 96.3%, 89%, 86.8% and 85% in the subgroup 1, 2, 3, 4 respectively. Overall, a statistically significant difference in BCSS rates was observed among the 4 subgroups (p=0.0036). On univariate analysis, post-menopause, older age (≥ 50 years), low PR and high Ki67 expression, poorly differentiated grade and size ≥ 2 cm as well as luminal B-like tumors (subgroups 2, 3, 4) were significantly associated with a worse BCSS. Multivariate analysis identified grade, size and subgroup classification of BC as independent prognostic markers of poorer outcome. In particular, subgroups 4, 3 and 2 displayed a significantly higher risk of BC-related death (HR=4.11; p=0.008; HR=3.43; p=0-007; HR=2.57; p=0.020, respectively) when compared to subgroup 1.ConclusionsOur results support the usefulness of PR and Ki67 levels as prognostic markers, corroborating their crucial role in the decision-making process of patients with luminal-like HER2 negative early BC. Clinical application of these parameters should be assessed prospectively.
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- 2022
33. Skin Toxicity as Predictor of Survival in Refractory Patients with RAS Wild-Type Metastatic Colorectal Cancer Treated with Cetuximab and Avelumab (CAVE) as Rechallenge Strategy
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Erika Martinelli, Teresa Troiani, Lucia Esposito, Nicola Normanno, Davide Ciardiello, Carmine Pinto, Evaristo Maiello, Chiara Cremolini, Tiziana Latiano, Vincenzo Famiglietti, Giuseppe Santabarbara, Giulia Martini, Antonio Avallone, Stefania Napolitano, Fortunato Ciardiello, Filippo Pietrantonio, Ciardiello, D., Famiglietti, V., Napolitano, S., Esposito, L., Normanno, N., Avallone, A., Latiano, T., Maiello, E., Pietrantonio, F., Cremolini, C., Santabarbara, G., Pinto, C., Troiani, T., Martinelli, E., Ciardiello, F., and Martini, G.
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Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Gastroenterology ,Article ,Refractory ,Statistical significance ,Internal medicine ,Medicine ,RC254-282 ,Chemotherapy ,Univariate analysis ,Cetuximab ,business.industry ,Hazard ratio ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,skin toxicity ,Rechallenge anti‐EGFR ,Oncology ,mCRC ,rechallenge anti-EGFR ,Biomarker (medicine) ,Immunotherapy ,MCRC ,Skin toxicity ,immunotherapy ,business ,medicine.drug - Abstract
The single-arm phase II CAVE mCRC trial evaluated the combination of cetuximab plus avelumab as rechallenge strategy in RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients, with clinical response to first-line anti-EGFR-based chemotherapy, who progressed and received a subsequent line of therapy. The correlation of skin toxicity (ST) and different clinico-molecular variables with overall survival (OS), progression-free survival (PFS) and response rate (RR) was assessed at univariate and multivariate analysis. A total of 33/77 (42.9%) patients experienced grade 2–3 ST and displayed median OS (mOS) of 17.8 months (CI 95%, 14.9–20.6), whereas 44/77 (57.1%) patients with grade 0–1 ST exhibited mOS of 8.2 months (CI 95%, 5.5–10.9), (hazard ratio (HR), 0.51, CI 95%, 0.29–0.89, p = 0.019). Median PFS (mPFS) was 4.6 months (CI 95%, 3.4–5.7) in patients with grade 2–3 ST, compared to patients with grade 0–1 ST with mPFS of 3.4 months (CI 95%, 2.7–4.1, HR, 0.49, CI 95%, 0.3–0.8, p = 0.004). Grade 2–3 ST (HR, 0.51, p = 0.019) and RAS/BRAF/EGFR WT circulating tumor DNA (ctDNA) (HR, 0.50, CI 95%, 0.27–0.9, p = 0.019) had a statistically significant effect on OS at univariate analysis. At the multivariate analysis, RAS/BRAF/EGFR WT ctDNA status maintained statistical significance (HR, 0.49, p = 0.023), whereas there was a trend towards ST grade 2–3 (HR, 0.54, CI 95%, 0.29–1.01, p = 0.054). Skin toxicity is a promising biomarker to identify patients with mCRC that could benefit of anti-EGFR rechallenge.
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- 2021
34. Chronic Chest Pain Control after Trans-Thoracic Biopsy in Mediastinal Lymphomas
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Giuseppe Gazzerro, Antonello Sica, Alfonso Fiorelli, Maria Teresa Di Dato, Alfonso Papa, Evangelista Sagnelli, Elisabetta Saracco, Stefano Caccavale, Paola Vitiello, Anna Maria Salzano, Caterina Sagnelli, Vincenzo Famiglietti, Marco Rispoli, Dario Tammaro, Massimiliano Creta, Mario Santagata, Beniamino Casale, Pietro Buonavolontà, Sica, A., Casale, B., Sagnelli, C., Di Dato, M. T., Rispoli, M., Santagata, M., Buonavolonta, P., Fiorelli, A., Vitiello, P., Caccavale, S., Creta, M., Salzano, A. M., Sagnelli, E., Saracco, E., Gazzerro, G., Famiglietti, V., Tammaro, D., and Papa, A.
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medicine.medical_specialty ,Leadership and Management ,medicine.medical_treatment ,Health Informatics ,Chest pain ,Article ,03 medical and health sciences ,0302 clinical medicine ,mediastinal j ,Health Information Management ,Mediastinal Lymphoma ,Biopsy ,medicine ,Paravertebral Block ,030212 general & internal medicine ,Thoracotomy ,Pathological ,medicine.diagnostic_test ,business.industry ,Health Policy ,Chronic pain ,medicine.disease ,Surgery ,030220 oncology & carcinogenesis ,trans-thoracic biopsy ,Etiology ,Medicine ,medicine.symptom ,business ,chronic pain - Abstract
Chest pain following a trans-thoracic biopsy often has multiple etiologies, especially in patients with lymphomas. Pathological neuronal mechanisms integrate with an overproduction of IL-6, TNF-α, IL1-β by macrophages and monocytes, which amplifies inflammation and pain. In consideration of this complex pathogenesis, international guidelines recommend diversified analgesia protocols: thoracic epidural, paravertebral block, and systemic administration of opioids. This study reports an attempt to reduce chest pain and prevent chronic pain in 51 patients undergoing trans-thoracic biopsy for mediastinal lymphoma. The entity of pain, measured 72nd hour after biopsy by the Numerical Rating Scale (NRS), was compared with that seen at a 6th month checkpoint in 46 patients. The pain decreased in all cases. At the 6th month checkpoint, among 31 opioid-treated patients, none of the 16 patients with NRS <, 6 within the 72nd hour post biopsy had developed chronic chest pain, while 8 of the 15 with higher values did (p <, 0.01). Of 10 patients undergoing thoracotomy and treated with opioids, eight had a NRS of no more than 2, of which six had no chronic pain. Of the twenty-one patients who underwent VATS biopsy and were treated with opioids, fifteen had NRS no greater than 2, of which ten had no chronic pain. Subgroups of patients biopsied under mediastinotomy or video-assisted thoracoscopic surgery (VATS) and treated with thoracic epidural analgesia (TEA) or PVB were too small for such analysis.
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- 2021
35. Retrospective Study of Regorafenib Versus TAS-102 Efficacy and Safety in Chemorefractory Metastatic Colorectal Cancer (mCRC) Patients: A Multi-institution Real Life Clinical Data
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N. Zanaletti, Teresa Troiani, Michela Milanesio, Elisabetta Fenocchio, Erika Martinelli, Pasquale Lombardi, Davide Ciardiello, Susanna Rosellò, P. Vitale, Stefania Napolitano, Giulia Martini, Andrés Cervantes, Vincenzo De Falco, Fortunato Ciardiello, Vincenzo Famiglietti, Vitale, P., Zanaletti, N., Famiglietti, V., De Falco, V., Cervantes, A., Rosello, S., Fenocchio, E., Milanesio, M., Lombardi, P., Ciardiello, D., Martini, G., Martinelli, E., Ciardiello, F., Troiani, T., and Napolitano, S.
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Oncology ,medicine.medical_specialty ,Pyrrolidines ,Real Life Clinical data ,Pyridines ,Colorectal cancer ,Trifluridine ,chemistry.chemical_compound ,Refractory ,Internal medicine ,Regorafenib ,medicine ,Humans ,Uracil ,Retrospective Studies ,business.industry ,Phenylurea Compounds ,Gastroenterology ,Retrospective cohort study ,medicine.disease ,TAS-102 ,Disease control ,Cancer treatment ,Clinical trial ,Drug Combinations ,chemistry ,mCRC ,Cohort ,chemorefractory ,regorafenib ,Colorectal Neoplasms ,business ,Thymine - Abstract
INTRODUCTION: There have been significant developments in colorectal cancer (CRC) research over the last few years, with the introduction of new agents that have been prolonged median overall survival of metastatic colorectal cancer (mCRC). These therapies have improved patient outcomes; however, despite significant progress in strategies for cancer treatment, their use is limited by development of resistant mechanism. Almost 30% of patients with refractory mCRC will remain good candidates for further treatment. Regorafenib and TAS-102 are novel antitumor agents for patients with refractory mCRC. However, it is unclear which patients may derive a survival benefit from these drugs in real-life clinical practice.; METHODS: We performed a retrospective analysis evaluating safety and efficacy of TAS-102 and regorafenib in a cohort of refractory mCRC patients, in 3 different centers between January 1 2018 and May 31 2020, with the aim of assessing the optimal sequence treatment for these 2 drugs.; RESULTS: One hundred and forty mCRC patients were included in the analysis. Of these patients, 64 received regorafenib and 76 received TAS-102 as first treatment. After progression, in the regorafenib 24 (37%) patients switched to secondary treatment with TAS-102, instead, in the TAS-102 group, among 76 patients, 29 (45%) patients switched to secondary treatment with regorafenib. Disease control was achieved in 8 (12.5%) of 64 patients in the regorafenib group and 17 (22.4%) of 76 patients in the TAS-102 group. In terms of efficacy, the PFS and OS were similar in both treatment groups for primary and secondary treatments. AEs reported in this analysis were mostly consistent with the known safety profiles of regorafenib and TAS-102 in previous clinical trials.; CONCLUSION: The present study is the first one to compare the activity of the two agents in a large cohort of chemo-refractory mCRC patients providing more details about the best sequence, to be incorporated in clinical practice. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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- 2021
36. Cetuximab rechallenge plus avelumab in pretreated patients with RAS Wild-type Metastatic Colorectal Cancer: The Phase 2 Single-Arm Clinical CAVE Trial
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Teresa Troiani, Federica Morano, M. Terminiello, Giuseppe Santabarbara, Evaristo Maiello, Davide Ciardiello, Carmine Pinto, Anna Nappi, Erika Martinelli, Vincenzo Famiglietti, Claudia Cardone, Alessandra Di Liello, C. Borrelli, Chiara Cremolini, Antonio Avallone, Filippo de Braud, Stefania Napolitano, N. Zanaletti, Daniela Renato, Lucia Esposito, Daniele Santini, Filippo Pietrantonio, Tiziana Latiano, Giulia Martini, Pietro Paolo Vitiello, Nicola Normanno, Francesca Marrone, Daniele Rossini, Fortunato Ciardiello, Alfredo Falcone, Martinelli, E., Martini, G., Famiglietti, V., Troiani, T., Napolitano, S., Pietrantonio, F., Ciardiello, D., Terminiello, M., Borrelli, C., Vitiello, P. P., De Braud, F., Morano, F., Avallone, A., Normanno, N., Nappi, A., Maiello, E., Latiano, T., Falcone, A., Cremolini, C., Rossini, D., Santabarbara, G., Pinto, C., Santini, D., Cardone, C., Zanaletti, N., Di Liello, A., Renato, D., Esposito, L., Marrone, F., and Ciardiello, F.
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Male ,Neuroblastoma RAS viral oncogene homolog ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Cetuximab ,Antibodies, Monoclonal, Humanized ,medicine.disease_cause ,Gastroenterology ,Proto-Oncogene Proteins p21(ras) ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Humans ,Adverse effect ,Original Investigation ,Chemotherapy ,business.industry ,Hazard ratio ,Middle Aged ,medicine.disease ,Oncology ,Female ,KRAS ,Colorectal Neoplasms ,business ,medicine.drug - Abstract
IMPORTANCE: Rechallenge therapy with anti–epidermal growth factor receptor (EGFR) drugs has been suggested in patients with chemo-refractory RAS wild-type (WT) metastatic colorectal cancer (mCRC) after initial response to anti–EGFR-based first-line treatment. The association of treatment with cetuximab plus avelumab with overall survival (OS) may be worthy of investigation in this setting. OBJECTIVE: To assess the efficacy and safety of cetuximab rechallenge therapy plus avelumab. DESIGN, SETTING, AND PARTICIPANTS: This single-arm, multicenter phase 2 trial enrolled patients from August 2018 to February 2020. Eligible patients with RAS WT mCRC had a complete or partial response to first-line chemotherapy plus anti-EGFR drugs, developed acquired resistance, and failed second-line therapy. Baseline circulating tumor DNA (ctDNA) for KRAS, NRAS, BRAF, and EGFR-S492R mutation analysis was done. INTERVENTIONS: Patients received avelumab (10 mg/kg every 2 weeks) and cetuximab (400 mg/m(2) and, subsequently, 250 mg/m(2) weekly) until disease progression or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES: The primary end point was OS. Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. RESULTS: Seventy-seven patients were enrolled (42 men, 35 women; median age, 63 years); 71 had microsatellite stable tumors (MSS), 3 microsatellite instability-high tumors (MSI-H), 3 unknown. The study met the primary end point, with median OS (mOS) of 11.6 months (95% CI, 8.4-14.8 months). Median PFS (mPFS) was 3.6 months (95% CI, 3.2-4.1 months). Common grade-3 adverse events were cutaneous eruption, 11 (14%), and diarrhea, 3 (4%). For 67 of 77 (87%) patients, baseline analysis of plasma circulating tumor DNA (ctDNA) for KRAS, NRAS, BRAF, and EGFR-S492R variations was feasible. Forty-eight patients had WT disease, whereas 19 had mutations. Patients with RAS/BRAF WT ctDNA had mOS of 17.3 months (95% CI, 12.5-22.0 months) compared with 10.4 months (95% CI, 7.2-13.6 months) in patients with mutated ctDNA (hazard ratio [HR], 0.49; 95% CI, 0.27-0.90; P = .02). The mPFS was 4.1 months (95% CI, 2.9-5.2 months) in RAS/BRAF WT patients compared with 3.0 months (95% CI, 2.6-3.5 months) in patients with mutated ctDNA (HR, 0.42; 95% CI, 0.23-0.75; P = .004). CONCLUSIONS AND RELEVANCE: The findings of this single-arm phase 2 trial suggest that cetuximab plus avelumab is an active, well tolerated rechallenge therapy in RAS WT mCRC. Plasma ctDNA analysis before treatment may allow selection of patients who could benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04561336
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- 2021
37. Feasibility of next-generation sequencing in clinical practice: results of a pilot study in the Department of Precision Medicine at the University of Campania ‘Luigi Vanvitelli’
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Stefania Napolitano, Davide Ciardiello, L. Poliero, Ferdinando De Vita, M. Terminiello, Morena Fasano, Emilio Francesco Giunta, Vincenzo De Falco, P. Vitale, Teresa Troiani, Francesca Carlino, Renato Franco, Raimondo Di Liello, Vincenzo Famiglietti, N. Zanaletti, V. Caputo, Carminia Maria Della Corte, Anna Ventriglia, Michele Orditura, Lucia Altucci, Giulia Martini, Floriana Morgillo, Fortunato Ciardiello, Erika Martinelli, Pietro Paolo Vitiello, De Falco, V., Poliero, L., Vitello, P. P., Ciardiello, D., Vitale, P., Zanaletti, N., Giunta, E. F., Terminiello, M., Caputo, V., Carlino, F., Di Liello, R., Ventriglia, A., Famiglietti, V., Martinelli, E., Morgillo, F., Orditura, M., De Vita, F., Fasano, M., Napolitano, S., Martini, G., Della Corte, C. M., Franco, R., Altucci, L., Ciardiello, F., and Troiani, T.
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Oncology ,Cancer Research ,medicine.medical_specialty ,foundationone ,Colorectal cancer ,Population ,medicine.disease_cause ,Breast cancer ,Internal medicine ,medicine ,Lung cancer ,education ,Original Research ,education.field_of_study ,Performance status ,business.industry ,comprehensive genomic profiling ,CGP ,Cancer ,medicine.disease ,NGS ,next-generation sequencing ,KRAS ,Ovarian cancer ,business - Abstract
Background The emerging role of next-generation sequencing (NGS) targeted panels is revolutionising our approach to cancer patients, providing information on gene alterations helpful for diagnosis and clinical decision, in a short time and with acceptable costs. Materials and methods In this work, we evaluated the clinical application of FoundationOne CDx test, a hybrid capture-based NGS. This test identifies alterations in 324 genes, tumour mutational burden and genomic signatures as microsatellite instability. The decision to obtain the NGS assay for a particular patient was done according to investigator's choice. Results Overall, 122 tumour specimens were analysed, of which 84 (68.85%) succeeded. The success rate was influenced by type of specimen formalin-fixed paraffin embedded (FFPE block vs FFPE slides), by origin of the sample (surgery vs biopsy) and by time of fixation (
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- 2020
38. Clinical Practice Use of Liquid Biopsy to Identify RAS/BRAF Mutations in Patients with Metastatic Colorectal Cancer (mCRC): A Single Institution Experience
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L. Poliero, Pietro Paolo Vitiello, P. Vitale, N. Zanaletti, V. Caputo, Francesca Marrone, Vincenzo Famiglietti, Claudia Cardone, Emilio Francesco Giunta, Teresa Troiani, C. Borrelli, Vincenzo De Falco, Alessandra Di Liello, Fortunato Ciardiello, M. Terminiello, Erika Martinelli, Michele Caraglia, Valentina Mattera Iacono, Renato Franco, Stefania Napolitano, G. Arrichiello, Ferdinando De Vita, Giulia Martini, Floriana Morgillo, Davide Ciardiello, Angela Lombardi, Vitiello, P. P., De Falco, V., Giunta, E. F., Ciardiello, D., Cardone, C., Vitale, P., Zanaletti, N., Borrelli, C., Poliero, L., Terminiello, M., Arrichiello, G., Caputo, Vincenzo, Famiglietti, V., Iacono, V. M., Marrone, F., Di Liello, A., Martini, G., Napolitano, S., Caraglia, M., Lombardi, A., Franco, R., De Vita, F., Morgillo, F., Troiani, T., Ciardiello, F., and Martinelli, E.
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ras testing ,0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,RAS testing ,acquired resistance ,anti-EGFR ,clonal evolution ,colorectal cancer ,liquid biopsy ,Concordance ,medicine.disease_cause ,lcsh:RC254-282 ,Somatic evolution in cancer ,Article ,03 medical and health sciences ,0302 clinical medicine ,Carcinoembryonic antigen ,Growth factor receptor ,Internal medicine ,medicine ,Liquid biopsy ,biology ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,KRAS ,business - Abstract
Tumor heterogeneity represents a possible cause of error in detecting predictive genetic alterations on tumor tissue and can be overcome by testing alterations in circulating tumor DNA (ctDNA) using liquid biopsy. We assessed 72 consecutive patients with a diagnosis of metastatic colorectal cancer (mCRC) using Idylla&trade, Biocartis, a fully automated platform that evaluates the most frequent mutations of KRAS, NRAS and BRAF genes. We correlated the results of liquid biopsy and standard tissue-based next generation sequencing (NGS) analyses to patient clinical features. The overall agreement was 81.94%. Concordance was 85.71% and 96.15% in treatment-naï, ve patients and in the patient subgroup with liver metastases, respectively. In liver metastases positive, treatment-naï, ve patients, sensitivity, specificity and positive predictive value (PPV) were 92.31%, 100% and 100%, respectively. Circulating mutational fraction (CMF) was significantly higher in patients with liver metastases and high carcinoembryonic antigen (CEA) levels. In a subgroup of patients pre-treated with anti-Epidermal Growth Factor Receptor (EGFR) agents, emerging KRAS mutations were evidenced in 33% of cases. Testing RAS/BRAF mutations on plasma using the Idylla&trade, Biocartis platform is feasible and reliable in mCRC patients in clinical practice.
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- 2019
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39. Induction of natural killer antibody-dependent cell cytotoxicity and of clinical activity of cetuximab plus avelumab in non-small cell lung cancer
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Maria Lucia Iacovino, Alessandro Morabito, Mario Capasso, Vincenzo Sforza, Vincenzo Famiglietti, Evaristo Maiello, Flora Cimmino, Giuseppe Viscardi, Morena Fasano, Achille Iolascon, Carminia Maria Della Corte, Giusi Barra, Francesca Sparano, Raimondo Di Liello, Vincenza Ciaramella, Fernando Paragliola, Fortunato Ciardiello, Floriana Morgillo, Fasano, M., Della Corte, C. M., Di Liello, R., Barra, G., Sparano, F., Viscardi, G., Iacovino, M. L., Paragliola, F., Famiglietti, V., Ciaramella, V., Cimmino, F., Capasso, M., Iolascon, A., Sforza, V., Morabito, A., Maiello, E., Ciardiello, F., and Morgillo, F.
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Cancer Research ,Lung Neoplasms ,NK cells ,Antibodies, Monoclonal, Humanized ,NSCLC ,lcsh:RC254-282 ,Avelumab ,chemistry.chemical_compound ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Lactate dehydrogenase ,cetuximab ,Humans ,Medicine ,NK cell ,Progression-free survival ,Cytotoxicity ,Lung cancer ,neoplasms ,Original Research ,Antibody-dependent cell-mediated cytotoxicity ,Cetuximab ,business.industry ,Antibody-Dependent Cell Cytotoxicity ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Killer Cells, Natural ,Oncology ,chemistry ,Immunoglobulin G ,Cancer research ,avelumab ,ADCC ,business ,Ex vivo ,medicine.drug - Abstract
Background Antibody-dependent cell-mediated cytotoxicity (ADCC) may mediate antitumour activity of IgG1-isotype monoclonal antibody (mAb), suggesting as potential treatment combination of IgG1-mAbs, anti-epidermal growth factor receptor cetuximab and anti-programmed death-ligand-1 avelumab. Methods We evaluated ADCC induction in lung cancer cells by lactate dehydrogenase (LDH) release assay. Antitumour activity and safety of cetuximab plus avelumab were explored in a single-arm proof-of-concept study in pre-treated non-small cell lung cancer (NSCLC) patients (pt) (Cetuximab-AVElumab-lung, CAVE-Lung). Search for predictive biomarkers of response was done. Results Avelumab plus cetuximab induced ADCC in NSCLC cells in vitro in presence of natural killers (NK) from healthy donors (HD) or NSCLC pt, as effectors. Sixteen relapsed NSCLC pt were treated with avelumab plus cetuximab. Antitumour activity was observed in 6/16 pt, defined by progression free survival (PFS) ≥8 months, with 4 of them still on treatment at data lock time (range, 14–19 months). Of note, 3/6 responders had received as previous line anti-programmed death-1 therapy. In responders, clinical benefit was accompanied by significant increase in LDH release over baseline at the first radiological evaluation (8 weeks) (p=0.01) and by early skin toxicity; while in the 10 non-responders, that had PFS ≤5 months, LDH release tends to reduce. Baseline circulating DNA levels were higher in non-responders compared with responders and HD (p=0.026) and decrease in responders during therapy. Mutations in DNA damage responsive family genes were found in responders. Conclusion Cetuximab and avelumab activates NSCLC pt NK cells. Ex vivo evaluation of ADCC, circulating DNA levels and early skin toxicity may predict response to cetuximab plus avelumab in NSCLC. EUDRACT 2017-004195-58
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- 2020
40. Three dimensional primary cultures for selecting human breast cancers that are sensitive to the anti-tumor activity of ipatasertib or taselisib in combination with anti-microtubule cytotoxic drugs
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Vincenzo Famiglietti, A. Diana, Michele Orditura, Fortunato Ciardiello, Elisena Franzese, Renato Franco, Iacopo Panarese, E. Procaccini, Floriana Morgillo, Michele Caraglia, A. Santoriello, C.M. Della Corte, Eva Lieto, F. De Vita, Anna Grimaldi, Angela Lombardi, Evaristo Maiello, Vincenza Ciaramella, Orditura, M., Della Corte, C. M., Diana, A., Ciaramella, V., Franzese, E., Famiglietti, V., Panarese, I., Franco, R., Grimaldi, A., Lombardi, A., Caraglia, M., Santoriello, A., Procaccini, E., Lieto, E., Maiello, E., De Vita, F., Ciardiello, F., and Morgillo, F.
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0301 basic medicine ,Drug ,media_common.quotation_subject ,Cell Culture Techniques ,Antineoplastic Agents ,Breast Neoplasms ,Drug resistance ,medicine.disease_cause ,Ipatasertib ,Piperazines ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Cell Line, Tumor ,Medicine ,Humans ,PI3K/AKT/mTOR pathway ,media_common ,Mutation ,business.industry ,Taselisib ,AKT ,Imidazoles ,High-Throughput Nucleotide Sequencing ,General Medicine ,medicine.disease ,Tubulin Modulators ,Oxazepines ,030104 developmental biology ,Pyrimidines ,Cell culture ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Three-dimensional cell culture ,Cancer research ,Surgery ,Female ,KRAS ,business ,Ex vivo model - Abstract
Two inhibitors of phosphatidylinositol 3-kinase (PI3K) pathway taselisib, targeting the mutant PI3K-subunit-alpha (PI3KA) and ipatasertib, AKT-inhibitor, are currently under clinical investigation in breast cancer (BC) patients. We have previously demonstrated the anti-tumor efficacy of these anti-PI3K/AKT-inibitors in combination with anti-microtubule drugs in human BC cell lines, through a complete cytoskeleton disorganization. In this work, we generated ex-vivo three-dimensional (3D) cultures from human BC as a model to test drug efficacy and to identify new molecular biomarkers for selection of BC patients suitable for anti-PI3K/AKT-inibitors treatment. We have established 3D cultures from 25/27 human BC samples, in which the ability of growth in vitro replicates the clinical and biological aggressiveness of the original tumors. According to the results of next generation sequencing analysis, a direct correlation was found between PI3KA mutations and the sensitivity in 3D models in vitro to taselisib and ipatasertib alone and combined with anti-microtubule agents. Moreover, mutations in HER and MAPK families related genes, including EGFR, KRAS and BRAF, were found in resistant samples, suggesting their potential role as negative predictive factors of response to these agents. Thus, we demonstrated that ex vivo 3D cultures from human BC patients allow a rapid and efficient drug screening for chemotherapies and targeted agents in genetically selected patients and represent an innovative model to identify new biomarkers of drug resistance.
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- 2018
41. Systemic-inflammation-based score can predict prognosis in metastatic gastric cancer patients before first-line chemotherapy
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Angelica Petrillo, Maria Maddalena Laterza, Luca Pompella, Fortunato Ciardiello, Erika Martinelli, Vincenzo Famiglietti, Gennaro Galizia, Michele Orditura, Jole Ventriglia, Giuseppe Tirino, Ferdinando De Vita, Annalisa Pappalardo, Petrillo, A, Laterza, Mm, Tirino, G, Pompella, L, Ventriglia, J, Pappalardo, A, Famiglietti, V, Martinelli, E, Ciardiello, F, Orditura, M, Galizia, G, and De Vita, F.
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0301 basic medicine ,Oncology ,Adult ,Blood Platelets ,Male ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Neutrophils ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Systemic inflammation ,Disease-Free Survival ,Metastatic gastric cancer ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,In patient ,Lymphocyte Count ,Aged ,Retrospective Studies ,Neutrophil-lymphocyte ratio ,Aged, 80 and over ,Inflammation ,Chemotherapy ,Performance status ,business.industry ,fungi ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,First line chemotherapy ,medicine.symptom ,business ,Platelet-lymphocyte ratio - Abstract
Aim: Systemic inflammatory response affects survival of gastric cancer (GC) patients. This study was carried out to create a prognostic inflammatory-based score to predict survival in metastatic GC (mGC) before first-line chemotherapy. Materials & methods: We studied the prognostic value of neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio in 151 patients with mGC at the diagnosis. Results: Median overall survival (OS) was significantly lower in patients with high NLR. Performance status 1–2 according to the Eastern Cooperative Oncology Group scale and NLR were predictors of shorter OS at multivariate analysis. Based on these results, we defined a prognostic OS score, showing a better median OS in favorable risk group. Conclusion: Elevated pretreatment NLR and Eastern Cooperative Oncology Group are independent predictors of shorter OS in mGC patients before first-line chemotherapy.
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- 2018
42. 17P Genomic profiling of non-oncogene-addicted aNSCLC using liquid biopsy. A single institution Italian experience.
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Liello, R Di, Viscardi, G, Sparano, F, Corte, C M Della, Iacovino, M L, Paragliola, F, Famiglietti, V, Liello, A Di, Ciardiello, F, and Morgillo, F
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- *
EPIDERMAL growth factor receptors , *PROTEIN-tyrosine kinases , *SQUAMOUS cell carcinoma - Abstract
Background cfDNA analysis could represent an alternative to invasive biopsy in patients with NSCLC to better understand disease profile. We report a real-world experience of genomic assessment of an Italian patients' cohort. Methods We evaluated 58 non-oncogene-addicted aNSCLC patients treated at our Institution from January 2018 to May 2019. All patients were characterized using cfDNA NGS Guardant360® platform (Guardant Health, Redwood City, CA). Association between a positive result (defined as cfDNA detected) and clinical features was assessed using logistic regression test. Using online library dataset (mycancergenome.org) and literature data, we divided patients in genomic clusters and performed a descriptive analysis. Results The median age of patients was 67 (range 38-85), 44 men and 14 women, 8.6% never smokers, 41.4% former and 50% current smokers. 14 patients (24.2%) had squamous cell carcinoma and 44 (75.8%) had non-squamous NSCLC, 50 of 58 at stage IV at the time of testing. Most patients were PS 0-1 per ECOG scale and has been treated with at least one systemic regimen before performing NGS. 47 of 58 patients (81%) has been considered positive at the analysis. No targetable genomic alterations per local authority has been found. More than 40 different mutated genes were detected, the most common alterations involved TP53 (60% of patients), KRAS (34%), PDGFRα (17%), EGFR (15% - not-TKI-sensitive), PI3KCA (15%), CDKN2A (15%). Chemotherapy (but not immunotherapy) and extra-thoracic radiotherapy before testing increased the probability to result positive at NGS of 4.5 and 2 folds respectively. Six mutational clusters have been identified. Most patients had genomic alterations in Replication Stress - DNA damage/repair, cell cycle - (72%) and Tyrosine Kinase Receptor/Growth Factor pathway (62%), less common mutations affected PI3K/AKT/mTOR and Hormone signaling (26% and 9% respectively). Conclusions Our experience demonstrated the feasibility of NGS-based NSCLC patients genomic profiling. The widespread of NGS platforms (and the subsequent reduction of costs) should encourage clinicians to use these methods with all patients to guarantee access to developing therapeutics and clinical trials. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure F. Ciardiello: Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer. F. Morgillo: Advisory / Consultancy: MSD; Advisory / Consultancy: Lilly; Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]
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- 2019
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43. Catalytic hydrodechlorination of 1,2,3-trichlorobenzene
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V. Famiglietti, Francesco Gioia, Fabio Murena, Gioia, Francesco, Famiglietti, V., and Murena, Fabio
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rifiuti tossici ,Environmental Engineering ,Hydrogen ,Waste management ,Health, Toxicology and Mutagenesis ,Batch reactor ,chemistry.chemical_element ,Trichlorobenzene ,Biodegradable waste ,Hexadecane ,Pollution ,clorobenzeni ,Incineration ,Catalysis ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,idrodeclorazione catalitica ,medicine ,Environmental Chemistry ,Waste Management and Disposal ,medicine.drug ,Bar (unit) - Abstract
Detoxification by catalytic hydrotreatment can be a valid alternative to thermal incineration for the disposal of hazardous organic waste liquids. With this aim, the hydrodechlorination of 1,2,3-trichlorobenzene on a Ni-Mo/γ-Al2O3 catalyst has been investigated experimentally and theoretically. The behaviour of this chemical in hydrotreatment is hopefully representative of that of many toxic chlorinated compounds. The experimental reaction runs were conducted in a stirred batch reactor in the presence of hydrogen, at constant pressure (pH2 = 100 bar), and using hexadecane as a reaction medium. The temperature, kept constant during each run, was varied in the range 200°C⩽T⩽350°C. The experimental results consisting of concentrations of reactant, reaction products and intermediates vs. time, permit the identification of the reaction network and its modification with temperature. The kinetic constants (and their temperature dependence) of the reactions which form the network are also determined.
- Published
- 1993
44. Overexpression of CCL-20 and CXCL-8 genes enhances tumor escape and resistance to cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with locally advanced and metastatic cutaneous squamous cell carcinoma.
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De Falco V, Napolitano S, Franco R, Zito Marino F, Formisano L, Esposito D, Suarato G, Napolitano R, Esposito A, Caraglia F, Giugliano MC, Cioli E, Famiglietti V, Bianco R, Argenziano G, Ronchi A, Ciardiello D, Nardone V, D'Ippolito E, Del Tufo S, Ciardiello F, and Troiani T
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- Humans, Male, Female, Aged, Aged, 80 and over, Tumor Escape drug effects, Tumor Escape genetics, Middle Aged, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors pharmacology, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor genetics, Programmed Cell Death 1 Receptor metabolism, Gene Expression Regulation, Neoplastic drug effects, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Agents, Immunological pharmacology, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized administration & dosage, Skin Neoplasms drug therapy, Skin Neoplasms genetics, Skin Neoplasms pathology, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Drug Resistance, Neoplasm genetics, Drug Resistance, Neoplasm drug effects, Interleukin-8 genetics, Interleukin-8 metabolism
- Abstract
Cemiplimab has demonstrated relevant clinical activity in cutaneous squamous cell carcinoma (cSCC) but mechanisms of primary and acquired resistance to immunotherapy are still unknown. We collected clinical data from locally advanced and/or metastatic cSSC patients treated with cemiplimab in two Italian University centers. In addition, gene expression analysis by using Nanostring Technologies platform to evaluate 770 cancer- and immune-related genes on 20 tumor tissue samples (9 responders and 11 non-responders to cemiplimab) was performed. We enrolled 81 patients with a median age of 82 years. After 16.4 months of median follow-up, 12- and 24-months PFS were 53% and 42%, respectively; while 12- and 24-months OS were 71% and 61%, respectively. Treatment was well tolerated. Overall response rate (ORR) was 58%, with a disease control rate (DCR) of 77.8%. The difference between genes expressed in responder versus non-responder patient samples was substantial, particularly for genes involved in immune system regulation. Cemiplimab-resistant tumors were associated with over-expression of CCL-20 and CXCL-8. Cemiplimab confirmed efficacy and safety data in real-life cSCC patients. Overexpression of CCL-20 and CXCL-8 could represent biomarkers of lack of response to immunotherapy., Competing Interests: S.N. had travel grants from Amgen, Merck outside of the submitted works. D.C. had travel support from Sanofi, BMS, Merck serono outside of the submitted works. F.C. was advisory board for Amgen, Servier, MSD, Merck, Roche, Pfizer, Bayer, Pierre Fabre, Eisai outside of the submitted work. T.T. was advisory board for Amgen, MSD, Pierre Fabre, Roche, Merck outside of the submitted work. All remaining authors have no competing interests., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)
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- 2024
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45. Temozolomide based treatment in glioblastoma: 6 vs. 12 months.
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Fasano M, Pirozzi M, De Falco V, Miceli CC, Farese S, Zotta A, Famiglietti V, Vitale P, Di Giovanni I, Brancati C, Carfora V, Solari D, Somma T, Cavallo LM, Cappabianca P, Conson M, Pacelli R, Ciardiello F, and Addeo R
- Abstract
The Stupp regimen remains the standard treatment for newly diagnosed glioblastomas, although the prognosis remains poor. Several temozolomide alternative schedules have been studied, with extended adjuvant treatment (>6 cycles of temozolomide) frequently used, although different trials have indicated contrasting results. Survival data of 87 patients who received 6 ('6C' group) or 12 ('12C' group) cycles of temozolomide were collected between 2012 and 2022. A total of 45 patients were included in the 6C group and 42 patients were included in the 12C group. Data on isocitrate dehydrogenase mutation and methylguanine-DNA-methyltransferase (MGMT) promoter methylation status were also collected. The 12C group exhibited statistically significantly improved overall survival [OS; 22.8 vs. 17.5 months; hazard ratio (HR), 0.47; 95% CI, 0.30-0.73; P=0.001] and progression-free survival (15.3 vs. 9 months; HR, 0.39; 95% CI, 0.25-0.62; P=0.001). However, in the subgroup analysis according to MGMT status, OS in the 12C group was significantly superior to OS in the 6C group only in the MGMT unmethylated tumors. The present data suggested that extended adjuvant temozolomide appeared to be more effective than the conventional six cycles., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Fasano et al.)
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- 2024
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46. Radiomic Parameters for the Evaluation of Response to Treatment in Metastatic Colorectal Cancer Patients with Liver Metastasis: Findings from the CAVE-GOIM mCRC Phase 2 Trial.
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Martinelli E, Ciardiello D, Martini G, Napolitano S, Del Tufo S, D'Ambrosio L, De Chiara M, Famiglietti V, Nacca V, Cardone C, Avallone A, Cremolini C, Pietrantonio F, Maiello E, Granata V, Troiani T, Cappabianca S, Ciardiello F, Nardone V, and Reginelli A
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- Humans, Female, Male, Middle Aged, Aged, Tomography, X-Ray Computed methods, Adult, Cetuximab administration & dosage, Cetuximab therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Progression-Free Survival, Aged, 80 and over, Radiomics, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Liver Neoplasms secondary, Liver Neoplasms drug therapy, Liver Neoplasms diagnostic imaging
- Abstract
Background: CAVE is a single arm, Phase 2 trial, that demonstrated anti-tumor activity of cetuximab rechallenge plus avelumab in patients with RAS wild type (wt) metastatic colorectal cancer (mCRC)., Objective: We conducted a post hoc analysis to identify potential radiomic biomarkers for patients with CRC liver metastasis (LM)., Patients and Methods: Patients with LM that could be measured by enhanced contrast phase computed tomography (CT) imaging at baseline and at first response evaluation were included. Multiple texture parameters were extracted with the LifeX Software. Delta-texture (D-TA) variations were calculated by comparing data at baseline and after treatment., Results: Overall, 55/77 patients (71%) had LM; 39 met the inclusion criteria for the current analysis. The D-TA parameters that significantly correlated at univariate analysis with median progression-free survival (mPFS) were Entropy
Histogram (p = 0.021), HomogeneityGLCM (p < 0.001) and DissimilarityGLCM (p = 0.002). At multivariate analysis, only HomogeneityGLCM resulted significant for PFS (p = 0.001). Patients (19/39, 48.7%) with reduction of HomogeneityGLCM experienced better mPFS (4.6 vs 2.9 months; HR 0.45; 95% CI 0.23-0.88; p = 0.021) and median overall survival (mOS) (17.3 vs 6.8 months; HR 0.40, 95% CI 0.21-0.80; p = 0.010). A trend to better mPFS, was also observed in patients with RAS/BRAF wt circulating tumor DNA and reduction of HomogeneityGLCM . Overall survival was significantly better in this subgroup of patients with low HomogeneityGLCM : mOS was 17.8 (95% CI 15.5-20.2) versus 6.8 months (95% CI 3.6-10.0) (HR 0.34, 95% CI 0.14-0.81; p = 0.016)., Conclusion: Reduction in the D-TA parameter HomogeneityGLCM by radiomic analysis correlates with improved outcomes in patients with LM receiving cetuximab rechallenge plus avelumab therapy. Larger prospective studies are needed to validate and confirm these findings., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)- Published
- 2024
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47. Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer: A Nonrandomized Controlled Trial.
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Ciardiello D, Martinelli E, Troiani T, Mauri G, Rossini D, Martini G, Napolitano S, Famiglietti V, Del Tufo S, Masi G, Santini D, Avallone A, Pietrantonio F, Lonardi S, Di Maio M, Zampino MG, Fazio N, Bardelli A, Siena S, Cremolini C, Sartore-Bianchi A, and Ciardiello F
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- Humans, Male, Middle Aged, Cetuximab therapeutic use, ErbB Receptors, Irinotecan, Panitumumab, Prospective Studies, Proto-Oncogene Proteins B-raf genetics, Retrospective Studies, Trifluridine, Female, Adult, Aged, Aged, 80 and over, Colonic Neoplasms, Liver Neoplasms drug therapy, Liver Neoplasms genetics, Rectal Neoplasms
- Abstract
Importance: The available evidence regarding anti-epidermal growth factor receptor (EGFR) inhibitor rechallenge in patients with refractory circulating tumor DNA (ctDNA) RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) is derived from small retrospective and prospective studies., Objective: To evaluate the efficacy of anti-EGFR rechallenge in patients with refractory ctDNA RAS/BRAF wt mCRC., Design, Setting, and Participants: This nonrandomized controlled trial used a pooled analysis of individual patient data from patients with RAS/BRAF wt ctDNA mCRC enrolled in 4 Italian trials (CAVE, VELO, CRICKET, and CHRONOS) and treated with anti-EGFR rechallenge between 2015 and 2022 (median [IQR] follow-up, 28.1 [25.8-35.0] months)., Intervention: Patients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy., Main Outcomes and Measures: Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were calculated. Exploratory subgroup analysis evaluating several clinical variables was performed. Safety was reported., Results: Overall, 114 patients with RAS/BRAF wt ctDNA mCRC (median [IQR] age, 61 [29-88] years; 66 men [57.9%]) who received anti-EGFR rechallenge as experimental therapy (48 received cetuximab plus avelumab, 26 received trifluridine-tipiracil plus panitumumab, 13 received irinotecan plus cetuximab, and 27 received panitumumab monotherapy) were included in the current analysis. Eighty-three patients (72.8%) had received 2 previous lines of therapy, and 31 patients (27.2%) had received 3 or more previous lines of therapy. The ORR was 17.5% (20 patients), and the DCR was 72.3% (82 patients). The median PFS was 4.0 months (95% CI, 3.2-4.7 months), and the median OS was 13.1 months (95% CI, 9.5-16.7 months). The subgroup of patients without liver involvement had better clinical outcomes. The median PFS was 5.7 months (95% CI, 4.8-6.7 months) in patients without liver metastasis compared with 3.6 months (95% CI, 3.3-3.9 months) in patients with liver metastasis (hazard ratio, 0.56; 95% CI, 0.37-0.83; P = .004). The median OS was 17.7 months (95% CI, 13-22.4 months) in patients without liver metastasis compared with 11.5 months (95% CI, 9.3-13.9 months) in patients with liver metastasis (hazard ratio, 0.63; 95% CI, 0.41-0.97; P = .04). Treatments showed manageable toxic effects., Conclusions and Relevance: These findings suggest that anti-EGFR rechallenge therapy has promising antitumor activity in patients with refractory ctDNA RAS/BRAF wt mCRC. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival., Trial Registration: ClinicalTrials.gov Identifiers: NCT02296203; NCT04561336; NCT03227926; NCT05468892.
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- 2024
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48. Panitumumab plus trifluridine/tipiracil as anti-EGFR rechallenge therapy in patients with refractory RAS wild-type metastatic colorectal cancer: Overall survival and subgroup analysis of the randomized phase II VELO trial.
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Napolitano S, Ciardiello D, De Falco V, Martini G, Martinelli E, Della Corte CM, Esposito L, Famiglietti V, Di Liello A, Avallone A, Cardone C, De Stefano A, Montesarchio V, Zampino MG, Fazio N, Di Maio M, Del Tufo S, De Vita F, Altucci L, Marrone F, Ciardiello F, and Troiani T
- Subjects
- Humans, Panitumumab therapeutic use, Trifluridine therapeutic use, Antineoplastic Combined Chemotherapy Protocols, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colonic Neoplasms etiology, Rectal Neoplasms etiology
- Abstract
The randomized phase II VELO trial showed that the addition of panitumumab to trifluridine/tipiracil significantly improves progression-free survival (PFS) as compared to trifluridine/tipiracil in third-line therapy in patients with refractory RAS wild-type (WT) metastatic colorectal cancer (mCRC). With longer follow-up, final overall survival results and posttreatment subgroup analysis are presented. Sixty-two patients with refractory RAS WT mCRC were randomly assigned to receive, as third-line therapy, trifluridine/tipiracil alone (arm A) or in combination with panitumumab (arm B). Primary endpoint was PFS; secondary endpoints included overall survival (OS) and overall response rate (ORR). Median OS was 13.1 months (95% CI 9.5-16.7) in arm A compared to 11.6 months (95% CI 6.3-17.0) in arm B (HR: 0.96, 95% CI 0.54-1.71, P = .9). To evaluate the impact of subsequent lines of treatment, subgroup analysis was performed for the 24/30 patients in arm A, that received fourth-line therapy after disease progression. Median PFS was 4.1 months (95% CI 1.44-6.83) for 17 patients treated with anti-EGFR rechallenge as compared to 3.0 months (95% CI 1.61-4.31) for seven patients that received other therapies (HR: 0.29, 95% CI 0.10-0.85, P = .024). Median OS from the start of fourth-line treatment was 13.6 months (95% CI 7.2-20), and 5.1 months (95% CI 1.8-8.3) for patients treated with anti-EGFR rechallenge vs other therapies, respectively (HR: 0.30, 95% CI 0.11-0.81, P = .019). Final results of the VELO trial support the role of anti-EGFR rechallenge in the continuum of care of patients with RAS/BRAF WT mCRC., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
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- 2023
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49. Real-world clinical outcome and safety of adjuvant therapy in stage III melanoma patients: Data from two Academic Italian Institutions.
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De Falco V, Suarato G, Napolitano R, Argenziano G, Famiglietti V, Amato A, Servetto A, Bianco R, Formisano L, Terrano V, Esposito A, Giugliano MC, Ciardiello D, Ciardiello F, Napolitano S, and Troiani T
- Subjects
- Humans, Retrospective Studies, Disease-Free Survival, Antineoplastic Combined Chemotherapy Protocols adverse effects, Adjuvants, Immunologic therapeutic use, Melanoma, Cutaneous Malignant, Melanoma drug therapy, Melanoma genetics, Skin Neoplasms genetics
- Abstract
Adjuvant immunotherapy (IO) and targeted therapy (TT) have improved relapse-free survival (RFS) in patients with stage III melanoma, although about 25% of them relapse within a year. However, real-world data on treatment efficacy and safety as well as management of treatment recurrences are still limited. We retrospectively analyzed 113 patients with stage III melanoma who received at least one cycle of anti-PD-1 (nivolumab or pembrolizumab) or dabrafenib + trametinib as adjuvant therapy. Most of patients included into the analyses harbor BRAV600E mutation (66.4%) and had a stage IIIC melanoma (63.7%). Immunotherapy was administered in 48.7% of patients, whereas targeted therapy in 51.3% At data cut-off, median RFS was not reached with 12- and 24-months RFS of 81% and 64%, respectively. No new adverse events were registered. Thirty patients (26.5%) relapsed, mainly at distant sites. Patient treated with IO recurred mostly during adjuvant treatment (ON-treatment) while patients treated with TT relapsed at the end of treatment (OFF-treatment). At relapse, surgery, radiotherapy and systemic therapy were used alone or in combination. Among patients who started a first-line therapy, an excellent response switching to a different treatment was observed. Real-world outcomes and safety of adjuvant treatment for resected stage III melanoma appear comparable to clinical trials data. Moreover, management of recurrences depends on type of relapse (loco-regional vs distant) and timing (during vs OFF treatment). Furthermore, patients who relapse after adjuvant TT respond well to subsequent anti-PD1 based therapy., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
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- 2023
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50. Panitumumab Plus Trifluridine-Tipiracil as Anti-Epidermal Growth Factor Receptor Rechallenge Therapy for Refractory RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial.
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Napolitano S, De Falco V, Martini G, Ciardiello D, Martinelli E, Della Corte CM, Esposito L, Famiglietti V, Di Liello A, Avallone A, Cardone C, De Stefano A, Montesarchio V, Zampino MG, Bordonaro R, Scartozzi M, Santini D, Di Maio M, De Vita F, Altucci L, Marrone F, Ciardiello F, and Troiani T
- Subjects
- Aged, Female, Humans, Male, Proto-Oncogene Proteins B-raf genetics, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Panitumumab therapeutic use, Trifluridine therapeutic use
- Abstract
Importance: Current third-line therapies for patients with metastatic colorectal cancer (MCRC) have limited efficacy. Rechallenge with epidermal growth factor receptor (EGFR) inhibitors for RAS wild-type (WT) MCRC may be valuable for these patients., Objective: To compare the anti-EGFR monoclonal antibody panitumumab plus standard-of-care trifluridine-tipiracil with trifluridine-tipiracil alone as third-line therapy for RAS WT MCRC., Design, Setting, and Participants: This phase 2 randomized clinical trial (RCT) was conducted in 7 Italian centers from June 2019 to April 2022. Patients with refractory RAS WT MCRC who had a partial or complete response to first-line chemotherapy plus an anti-EGFR monoclonal antibody and an anti-EGFR drug-free interval of 4 or more months during second-line therapy were included., Interventions: Patients were randomized 1:1 to receive panitumumab plus trifluridine-tipiracil or trifluridine-tipiracil alone., Main Outcomes and Measures: The primary end point was progression-free survival (PFS). Circulating tumor DNA (ctDNA) extended sequence variation analysis was performed in a subgroup of patients., Results: Of 62 included patients, 31 received panitumumab plus trifluridine-tipiracil (19 [61.3%] male; median age, 65 years [range, 39-81 years]) and 31 received trifluridine-tipiracil alone (17 [54.8%] male; median age, 66 years [range, 32-82 years]). The primary end point was met. Median PFS was 4.0 months (95% CI, 2.8-5.3 months) in the panitumumab plus trifluridine-tipiracil arm vs 2.5 months (95% CI, 1.4-3.6 months) in the trifluridine-tipiracil only (hazard ratio [HR], 0.48; 95% CI, 0.28-0.82; P = .007). Pretreatment plasma RAS/BRAF WT ctDNA identified patients obtaining prolonged clinical benefit with panitumumab plus trifluridine-tipiracil compared with trifluridine-tipiracil, with PFS rates at 6 months of 38.5% vs 13.0% and at 12 months of 15.4% vs 0%. A ctDNA liquid-biopsy extended mutation analysis by FoundationOne Liquid CDx (profiling 324 genes) was performed in a subgroup of patients with baseline plasma RAS/BRAF WT ctDNA; in 15 of 23 patients (65.2%) whose tumors were WT for KRAS, NRAS, BRAFV600E, EGFR, ERBB2, MAP2K1, and PIK3CA, median PFS was 6.4 months (95% CI, 3.7-9.2 months). Within this group of 15 patients, 2 (13.3%) had partial response, 11 (73.3%) had stable disease, and 2 (13.3%) had disease progression as best response., Conclusions and Relevance: In this RCT, third-line treatment with the anti-EGFR monoclonal antibody panitumumab plus the standard-of-care trifluridine-tipiracil resulted in improved PFS compared with treatment with trifluridine-tipiracil alone among patients with refractory RAS WT MCRC. The findings support the clinical utility of liquid biopsy-guided anti-EGFR rechallenge therapy for refractory RAS WT MCRC., Trial Registration: ClinicalTrials.gov Identifier: NCT05468892.
- Published
- 2023
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