31 results on '"Auclin, Edouard"'
Search Results
2. Second-line treatment outcomes after progression from first-line chemotherapy plus immunotherapy in patients with advanced non-small cell lung cancer
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Auclin, Edouard, Benitez-Montanez, Jose, Tagliamento, Marco, Parisi, Francesca, Gorria, Teresa, Garcia-Campelo, Rosario, Dempsey, Naomi, Pinato, David J., Reyes, Roxana, Albarrán-Artahona, Víctor, Dall'Olio, Filippo, Soldato, Davide, Hendriks, Lizza, Nana, Frank Aboubakar, Tonneau, Marion, Lopez-Castro, Rafael, Nadal, Ernest, Kazandjian, Suzanne, Muanza, Thierry, Blanc-Durand, Félix, Fabre, Elizabeth, Castro, Natalia, Arasanz, Hugo, Rochand, Adrien, Besse, Benjamin, Routy, Bertrand, and Mezquita, Laura
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- 2023
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3. Prognostic scores including peripheral blood-derived inflammatory indices in patients with advanced non-small-cell lung cancer treated with immune checkpoint inhibitors
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Rebuzzi, Sara Elena, Prelaj, Arsela, Friedlaender, Alex, Cortellini, Alessio, Addeo, Alfredo, Genova, Carlo, Naqash, Abdul Rafeh, Auclin, Edouard, Mezquita, Laura, and Banna, Giuseppe Luigi
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- 2022
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4. Brief Report: Severe Sotorasib-Related Hepatotoxicity and Non-Liver Adverse Events Associated With Sequential Anti–Programmed Cell Death (Ligand)1 and Sotorasib Therapy in KRASG12C-Mutant Lung Cancer.
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Chour, Ali, Denis, Julie, Mascaux, Céline, Zysman, Maeva, Bigay-Game, Laurence, Swalduz, Aurélie, Gounant, Valérie, Cortot, Alexis, Darrason, Marie, Fallet, Vincent, Auclin, Edouard, Basse, Clémence, Tissot, Claire, Decroisette, Chantal, Bombaron, Pierre, Giroux-Leprieur, Etienne, Odier, Luc, Brosseau, Solenn, Creusot, Quentin, and Gueçamburu, Marina
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- 2023
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5. Durvalumab consolidation in patients with unresectable stage III non-small cell lung cancer with driver genomic alterations.
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Riudavets, Mariona, Auclin, Edouard, Mosteiro, Miguel, Dempsey, Naomi, Majem, Margarita, Lobefaro, Riccardo, López-Castro, Rafael, Bosch-Barrera, Joaquim, Pilotto, Sara, Escalera, Elena, Tagliamento, Marco, Mosquera, Joaquin, Zalcman, Gerard, Aboubakar-Nana, Frank, Ponce, Santiago, Dal Maso, Alessandro, Spotti, Martina, Mielgo-Rubio, Xabier, Mussat, Elodie, and Reyes, Roxana
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THERAPEUTIC use of monoclonal antibodies , *LUNG cancer , *RESEARCH , *ADENOCARCINOMA , *GENETIC mutation , *CONFIDENCE intervals , *TIME , *RETROSPECTIVE studies , *TUMOR classification , *CHEMORADIOTHERAPY , *GENOMICS , *SURVIVAL analysis (Biometry) , *DESCRIPTIVE statistics , *PROGRESSION-free survival - Abstract
Durvalumab is the standard-of-care as consolidation therapy after chemo-radiotherapy in stage III unresectable non-small cell lung cancer (NSCLC); however, its activity across patients with NSCLC harbouring driver genomic alterations (dGA) is poorly characterised. Multicentre retrospective study including patients with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and October 2020 at 26 centres in Europe and America. Clinical and biological data were collected; dGA included: EGFR / BRAF / KRAS mutations (m) and ALK/ROS1 rearrangements (r). We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA. Out of 323 patients included, 43 patients had one dGA: KRAS m (n = 26; 8 G12C), EGFR m (n = 8; 6 del19/ex21), BRAF m (n = 5; 4 V600E) and ALK r (n = 4). The median age was 66 years [39–84], gender ratio 1:1, with 98% performance status (PS) 0–1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n = 4 missing). In the whole cohort, the median PFS was 17.5 months (mo.) (95% CI, 13.2–24.9) and median OS 47 mo (95%CI, 47-not reached [NR]). No statistically significant differences in terms of the median PFS were observed between patients with dGA vs. non-dGA: 14.9 mo (95% CI, 8.1-NR) vs. 18 mo. (95% CI, 13.4–28.3) (P = 1.0); however, when analysed separately: the median PFS was NR (11.3-NR) in the KRAS m G12C vs. 8.1 mo (5.8-NR) in the EGFR m del19/ex21 vs. 7.8 mo (7.7-NR) in the BRAF m V600E/ ALK r (P = 0.02). We observed limited activity of durvalumab consolidation in patients with stage III unresectable NSCLC with EGFR/BRAF m and ALK r but not for those harbouring KRAS m. Larger prospective studies are needed to confirm these findings. • Similar treatment outcomes to PACIFIC phase III trial. • Different benefits of durvalumab consolidation based on oncogenic alterations. • Significant increase in PFS with durvalumab in patients with KRAS mutations. • ALK- rearranged NSCLC seem to benefit the least to durvalumab consolidation. • Largest retrospective study evaluating durvalumab in oncogenic addicted stage III NSCLC. [ABSTRACT FROM AUTHOR]
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- 2022
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6. First-line chemotherapy with raltitrexed in metastatic colorectal cancer: an Association des Gastro-entérologues Oncologues (AGEO) multicentre study.
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Gallois, Claire, Hafliger, Emilie, Auclin, Edouard, Perret, Audrey, Coutzac, Clélia, Turpin, Anthony, Pellat, Anna, Randrian, Violaine, Basile, Debora, Faroux, Roger, Pernot, Simon, Locher, Christophe, Hautefeuille, Vincent, Dubreuil, Olivier, Palmieri, Lola-Jade, Dior, Marie, Artru, Pascal, and Taieb, Julien
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In case of contraindication or intolerance to fluoropyrimidines, raltitrexed is a validated alternative in metastatic colorectal cancer (mCRC), associated or not with oxaliplatin. Little is known about the outcomes of raltitrexed combined with irinotecan or targeted therapies. This retrospective multicentre study enroled mCRC patients treated with first-line raltitrexed-based chemotherapy. Treatment-related toxicities were recorded. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start. 75 patients were treated with raltitrexed alone, TOMOX, or TOMIRI with or without bevacizumab. Grade 3–4 adverse events were seen in 31% of patients, without significant difference between the different treatment schedules. amongst the 36 patients with a history of fluoropyrimidine-induced cardiac toxicity, none developed cardiovascular events on raltitrexed. Median PFS and OS were 10.6 (95% CI 8.2 – 13.1) and 27.4 months (95% CI 24.1–38.1), respectively. Considering the chemotherapy regimen, TOMOX was significantly associated with better PFS and OS compared to TOMIRI and raltitrexed alone. In patients with mCRC not eligible for fluoropyrimidines, first-line raltitrexed-based chemotherapy had an acceptable safety profile. PFS and OS were consistent with usual survival data in mCRC, and significantly better in patients treated with TOMOX, independently of associated targeted therapies. [ABSTRACT FROM AUTHOR]
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- 2022
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7. High Prevalence of Somatic Oncogenic Driver Alterations in Patients With NSCLC and Li-Fraumeni Syndrome.
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Mezquita, Laura, Jové, Maria, Nadal, Ernest, Kfoury, Maria, Morán, Teresa, Ricordel, Charles, Dhooge, Marion, Tlemsani, Camille, Léna, Hervé, Teulé, Alex, Álvarez, Jose-Valero, Raimbourg, Judith, Hiret, Sandrine, Lacroix, Ludovic, Menéndez, Mireia, Saldaña, Juana, Brunet, Joan, Lianes, Pilar, Coupier, Isabelle, and Auclin, Edouard
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- 2020
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8. Efficacy and Safety of Aflibercept in Combination With Chemotherapy Beyond Second-Line Therapy in Metastatic Colorectal Carcinoma Patients: An AGEO Multicenter Study.
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Auvray, Marie, Tougeron, David, Auclin, Edouard, Moulin, Valérie, Artru, Pascal, Hautefeuille, Vincent, Hammel, Pascal, Lecomte, Thierry, Locher, Christophe, Sickersen, Gaëlle, Coriat, Romain, Lecaille, Cédric, Vernerey, Dewi, Taieb, Julien, and Pernot, Simon
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- 2020
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9. Circulating Tumor DNA Analysis for Patients with Oncogene-Addicted NSCLC With Isolated Central Nervous System Progression.
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Aldea, Mihaela, Hendriks, Lizza, Mezquita, Laura, Jovelet, Cécile, Planchard, David, Auclin, Edouard, Remon, Jordi, Howarth, Karen, Benitez, Jose Carlos, Gazzah, Anas, Lavaud, Pernelle, Naltet, Charles, Lacroix, Ludovic, de Kievit, Frank, Morris, Clive, Green, Emma, Ngo-Camus, Maud, Rouleau, Etienne, Massard, Christophe, and Caramella, Caroline
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- 2020
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10. Activity of EGFR Tyrosine Kinase Inhibitors in NSCLC With Refractory Leptomeningeal Metastases.
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Flippot, Ronan, Biondani, Pamela, Auclin, Edouard, Xiao, Dingyu, Hendriks, Lizza, Le Rhun, Emilie, Leduc, Charlotte, Beau-Faller, Michèle, Gervais, Radj, Remon, Jordi, Adam, Julien, Planchard, David, Lavaud, Pernelle, Naltet, Charles, Caramella, Caroline, Le Pechoux, Cécile, Lacroix, Ludovic, Gazzah, Anas, Mezquita, Laura, and Besse, Benjamin
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- 2019
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11. Outcome of Patients with Non-Small Cell Lung Cancer and Brain Metastases Treated with Checkpoint Inhibitors.
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Hendriks, Lizza E.L., Henon, Clemence, Auclin, Edouard, Mezquita, Laura, Ferrara, Roberto, Audigier-Valette, Clarisse, Mazieres, Julien, Lefebvre, Corentin, Rabeau, Audrey, Le Moulec, Sylvestre, Cousin, Sophie, Duchemann, Boris, le Pechoux, Cecile, Botticella, Angela, Ammari, Samy, Gazzah, Anas, Caramella, Caroline, Adam, Julien, Lechapt, Emmanuèle, and Planchard, David
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- 2019
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12. Immune-Related Adverse Events and Outcomes in Patients with Advanced Non-Small Cell Lung Cancer: A Predictive Marker of Efficacy?
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Remon, Jordi, Reguart, Noemí, Auclin, Edouard, and Besse, Benjamin
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- 2019
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13. Refining adjuvant therapy for non-metastatic colon cancer, new standards and perspectives.
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Taieb, Julien, André, Thierry, and Auclin, Edouard
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Colon cancer is the third most frequent cancer in males and the second in females. Approximately 75% are diagnosed at a localized stage. Recurrence occurs in 30% of patients when there is nodal involvement (stage III) due to micrometastatic spreading. To date only chemotherapeutic drugs such as fluoropyrimidines or oxaliplatin have proven effective to kill this residual disease and are currently recommended by scientific societies. To improve patient management in the near future, recent research has focused on new ways of using currently available agents, tools to better define each individual patient prognosis more clearly so as to tailor adjuvant treatment, and molecular profiling to identify specific subgroups of patients with tumors that may benefit from specific therapeutic approaches. In this review, we will focus on current scientific knowledge on adjuvant treatment in localized colon cancer, the duration and timing of adjuvant therapy and the perspectives for better selection of patients who will benefit from adjuvant treatments. [ABSTRACT FROM AUTHOR]
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- 2019
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14. Second-line targeted therapies after nivolumab-ipilimumab failure in metastatic renal cell carcinoma.
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Auvray, Marie, Auclin, Edouard, Barthelemy, Philippe, Bono, Petri, Kellokumpu-Lehtinen, Pirkko, Gross-Goupil, Marine, De Velasco, Guillermo, Powles, Thomas, Mouillet, Guillaume, Vano, Yann-Alexandre, Gravis, Gwenaëlle, Mourey, Loïc, Priou, Franck, Rolland, Frédéric, Escudier, Bernard, and Albiges, Laurence
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VASCULAR endothelial growth factor antagonists , *IPILIMUMAB , *METASTASIS , *RENAL cell carcinoma , *PROTEIN-tyrosine kinase inhibitors , *TREATMENT effectiveness , *MEDICAL records , *RETROSPECTIVE studies , *TREATMENT duration , *PROGNOSIS , *THERAPEUTICS - Abstract
Abstract Background Nivolumab-ipilimumab demonstrated a survival benefit over sunitinib in first-line setting for metastatic renal cell carcinomas (mRCCs) and is becoming a new standard of care for naïve patients with intermediate or poor risk prognosis (International mRCC Database Consortium). The efficacy of subsequent vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) after nivolumab-ipilimumab failure remains unclear. Methods Medical records of mRCC patients treated with nivolumab-ipilimumab, who received subsequent TKI, as part of Checkmate 214 study were reviewed in 13 institutions. Baseline characteristics, outcome data including progression-free survival (PFS), response, overall survival (OS) and toxicities were retrospectively collected. Results Overall 33 patients received subsequent TKI after nivolumab-ipilimumab failure. Median follow-up from start of subsequent TKI is 22 months (19–NR). Best response was assessed in 30 patients: 12 partial responses (36%), 13 stable diseases (39%) and five progressive diseases (15%). Median PFS from start of TKI was 8 months [5–13]. Median PFS with first-generation (sunitinib/pazopanib) and second-generation TKI (axitinib/cabozantinib) was 8 months [5–16] and 7 months (5–NA), respectively. PFS in second line was significantly longer in patients with a long first-line duration of response to the double immune checkpoint blockade (≥6 months) with 8 versus 5 months for short responder (<6 months) (p = 0.03). OS rate was 54% at 12 months. Toxicity was as expected: 42% developed at least one toxicity grade ≥3. Conclusion This is the first report of outcomes with TKI, after first-line nivolumab-ipilimumab failure. Median PFS suggests a sustained benefit of TKI and supports trials investigating the optimal sequence. Highlights • First report of tyrosine kinase inhibitor (TKI) activity in patients after nivolumab-ipilimumab failure in mRCC. • Median TKIs progression free survival is 8 months (95% confidence interval: 5–13). • No difference was observed between first and second generation of TKI. • 75% of patients had a clinical benefit with 36% of partial response. • Investigating the optimal sequence for each patient must be the next priority. [ABSTRACT FROM AUTHOR]
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- 2019
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15. Clinical and Translational Implications of RET Rearrangements in Non-Small Cell Lung Cancer.
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Ferrara, Roberto, Auger, Nathalie, Auclin, Edouard, and Besse, Benjamin
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- 2018
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16. Immunosenescence and immunecheckpoint inhibitors in non-small cell lung cancer patients: Does age really matter?
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Ferrara, Roberto, Mezquita, Laura, Auclin, Edouard, Chaput, Nathalie, and Besse, Benjamin
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Immunotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer (NSCLC), extending overall survival, with a favorable safety profile. However, there is still a gap of knowledge about the efficacy of immune checkpoint inhibitors (ICIs) in elderly patients. Data from randomized clinical trials testing ICIs are conflicting and often lack adequate statistical power. Although two large meta-analyses suggested an absence of a significant survival benefit in patients older than 75years, expanded access programs and retrospective cohort studies of ICIs in the real-life setting, showed comparable survival outcomes and safety profiles between older and younger patients. In this complex scenario, a further unresolved issue is the potential correlation between older age and immunotherapy primary resistance, a phenomenon probably linked to the continuous and progressive remodeling of immune functions with ageing, known as immunosenescence. Defining the role of ICIs in elderly NSCLC patients and exploring the molecular mechanisms underlying a possible lack of benefit or even accelerated tumor growth during immunotherapy are two major challenges for future research in this field of cancer treatment. In this review, we describe the major hallmarks of immunosenescence and we summarize the existing clinical data of ICIs in elderly NSCLC patients. [ABSTRACT FROM AUTHOR]
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- 2017
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17. Clinical outcomes by infusion timing of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer.
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Rousseau, Adrien, Tagliamento, Marco, Auclin, Edouard, Aldea, Mihaela, Frelaut, Maxime, Levy, Antonin, Benitez, Jose C., Naltet, Charles, Lavaud, Pernelle, Botticella, Angela, Grecea, Miruna, Chaput, Nathalie, Barlesi, Fabrice, Planchard, David, and Besse, Benjamin
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LUNG cancer , *IMMUNE checkpoint inhibitors , *CONFIDENCE intervals , *MULTIVARIATE analysis , *STEROIDS , *LOG-rank test , *REGRESSION analysis , *RETROSPECTIVE studies , *TREATMENT effectiveness , *SURVIVAL analysis (Biometry) , *PROPORTIONAL hazards models , *OVERALL survival - Abstract
We aimed to determine whether immune checkpoint inhibitors (ICI) time-of-day infusion might influence the survival of patients with advanced non-small cell lung cancer (NSCLC). We retrospectively analysed patients who received single-agent anti-PD-(L)1 therapy in any line between 2016 and 2021. We calculated by Cox regression models the association between the proportion of ICI infusions received after 16:30h and overall survival (OS) and progression-free survival (PFS). 180 patients were included, 77% received ICI as second- or further-line (median of 12 infusions/patient). The median age was 65 years (IQR 57–70), 112 patients (62%) were male, 165 (92%) were current or former tobacco smokers, 140 (78%) had performance status (PS) 0 or 1, 26 (14%) were on steroid therapy at ICI initiation. Histology was non-squamous for 139 (77%), the median number of metastatic sites was 3, and 33% had brain metastases. Patients who received at least 20% of ICI infusions after 16:30h (65 out of 180, 36%) had a statistically significant shorter median PFS as compared with patients receiving less than 20% of infusions in the evening (4.9 vs 9.4 months, log-rank p = 0.020), while numerical but not statistical shorter OS was observed (14.0 vs 26.2 months, log-rank p = 0.090). In the multivariate analysis, receiving at least 20% of evening infusions did not significantly increase the risk of death, while PS and line of treatment were significantly correlated with the OS. On the contrary, a proportion of ICI administration after 16:30h ≥20% conferred an HR for the PFS of 1.44 (95% CI: 1.01–2.05, p = 0.043), but this prognostic effect was not found when including in the model the total number of ICI infusions received (HR 1.20, 95% CI: 0.83–1.75, p = 0.329). Time-of-day infusion of ICI may impact the survival of patients with advanced NSCLC. Underlying prognostic characteristics and the number of infusions received could represent conceivable confounding factors, linked to increased variance related to ICI infusion timing. Nonetheless, further studies may unravel chronobiological mechanisms modulating ICI efficacy. • Does immune checkpoint inhibitors (ICI) time-of-day infusion impact on survival? • Retrospective study, advanced NSCLC patients receiving single-agent ICI in any line. • Non-significant shorter OS in patients receiving ≥20% ICI infusions in the evening. • Significant shorter PFS in patients receiving ≥20% ICI infusion in the evening. • Chronobiological mechanisms modulating ICI efficacy should be investigated. [ABSTRACT FROM AUTHOR]
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- 2023
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18. Erratum to 'Second-line targeted therapies after nivolumab-ipilimumab failure in metastatic renal cell carcinoma' [Eur J Cancer 108 (February 2019) 33–40].
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Auvray, Marie, Auclin, Edouard, Barthelemy, Philippe, Bono, Petri, Kellokumpu-Lehtinen, Pirkko, Gross-Goupil, Marine, De Velasco, Guillermo, Powles, Thomas, Mouillet, Guillaume, Vano, Yann-Alexandre, Gravis, Gwenaëlle, Mourey, Loïc, Priou, Franck, Rolland, Frédéric, Escudier, Bernard, and Albiges, Laurence
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PROTEIN-tyrosine kinase inhibitors , *VASCULAR endothelial growth factor antagonists , *METASTASIS , *RENAL cell carcinoma , *THERAPEUTICS - Published
- 2019
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19. Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics.
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Mezquita, Laura, Preeshagul, Isabel, Auclin, Edouard, Saravia, Diana, Hendriks, Lizza, Rizvi, Hira, Park, Wungki, Nadal, Ernest, Martin-Romano, Patricia, Ruffinelli, Jose C., Ponce, Santiago, Audigier-Valette, Clarisse, Carnio, Simona, Blanc-Durand, Felix, Bironzo, Paolo, Tabbò, Fabrizio, Reale, Maria Lucia, Novello, Silvia, Hellmann, Matthew D., and Sawan, Peter
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LUNG cancer prognosis , *LUNG cancer , *DRUG efficacy , *FLOW cytometry , *IMMUNE checkpoint inhibitors , *CLINICAL trials , *CANCER chemotherapy , *NEUTROPHILS , *CANCER patients , *COMPARATIVE studies , *LEUKOCYTE count , *DESCRIPTIVE statistics , *IMMUNOPHENOTYPING , *SURVIVAL analysis (Biometry) , *TUMOR markers , *IMMUNOTHERAPY , *LONGITUDINAL method , *THERAPEUTICS , *EVALUATION - Abstract
dNLR at the baseline (B), defined by neutrophils/[leucocytes-neutrophils], correlates with immune-checkpoint inhibitor (ICI) outcomes in advanced non–small-cell lung cancer (aNSCLC). However, dNLR is dynamic under therapy and its longitudinal assessment may provide data predicting efficacy. We sought to examine the impact of dNLR dynamics on ICI efficacy and understand its biological significance. aNSCLC patients receiving ICI at 17 EU/US centres were included [Feb/13-Jun/18]. As chemotherapy-only group was evaluated (NCT02105168). dNLR was determined at (B) and at cycle2 (C2) [dNLR≤3 = low]. B+C2 dNLR were combined in one score: good = low (B+C2), poor = high (B+C2), intermediate = other situations. In 57 patients, we prospectively explored the immunophenotype of circulating neutrophils, particularly the CD15+CD244-CD16 low cells (immature) by flow cytometry. About 1485 patients treatment with ICI were analysed. In ICI-treated patients, high dNLR (B) (~1/3rd) associated with worse progression-free (PFS)/overall survival (OS) (HR 1.56/HR 2.02, P < 0.0001) but not with chemotherapy alone (N = 173). High dNLR at C2 was associated with worse PFS/OS (HR 1.64/HR 2.15, P < 0.0001). When dNLR at both time points were considered together, those with persistently high dNLR (23%) had poor survival (mOS = 5 months (mo)), compared with high dNLR at one time point (22%; mOS = 9.2mo) and persistently low dNLR (55%; mOS = 18.6mo) (P < 0.0001). The dNLR impact remained significant after PD-L1 adjustment. By cytometry, high rate of immature neutrophils (B) (30/57) correlated with poor PFS/OS (P = 0.04; P = 0.0007), with a 12-week death rate of 49%. The dNLR (B) and its dynamics (C2) under ICI associate with ICI outcomes in aNSCLC. Persistently high dNLR (B+C2) correlated with early ICI failure. Immature neutrophils may be a key subpopulation on ICI resistance. • Baseline dNLR (B) and its dynamics (C2) associate with ICI outcome in advanced NSCLC. • The dNLR (B+C2) can improve the prediction of ICI outcomes vs. (B). • The impact of dNLR on survival remained significant after PD-L1 adjustment. • The dNLR is a simple biomarker that should be validated in clinical trials. • Circulating immature neutrophils can be key on ICI resistance. [ABSTRACT FROM AUTHOR]
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- 2021
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20. Letter to the Editor about Sorich et al.
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Auclin, Edouard, Besse, Benjamin, and Mezquita, Laura
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- 2019
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21. Indoor Radon in EGFR- and BRAF-Mutated and ALK-Rearranged Non-Small-Cell Lung Cancer Patients.
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Mezquita, Laura, Benito, Amparo, Ruano-Raviña, Alberto, Zamora, Javier, Olmedo, Maria Eugenia, Reguera, Pablo, Madariaga, Ainhoa, Villamayor, María, Cortez, Silvia Patricia, Gorospe, Luis, Santón, Almudena, Mayoralas, Sagrario, Hernanz, Raúl, Cabañero, Alberto, Auclin, Edouard, Carrato, Alfredo, and Garrido, Pilar
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- 2019
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22. Efficacy and safety of cabozantinib rechallenge in metastatic renal cell carcinoma: A retrospective multicentric study.
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Baudry, Edwige, Naoun, Natacha, Auclin, Edouard, Saldana, Carolina, Barthelemy, Philippe, Geoffrois, Lionnel, Thibault, Constance, de Vries-Brilland, Manon, Borchiellini, Delphine, Maillet, Denis, Hirsch, Laure, Vauchier, Charles, Carril-Ajuria, Lucia, Colomba, Emeline, Bernard-Tessier, Alice, Escudier, Bernard, Flippot, Ronan, and Albigès, Laurence
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THERAPEUTIC use of antineoplastic agents , *RENAL cell carcinoma , *DRUG efficacy , *CONFIDENCE intervals , *METASTASIS , *ANTINEOPLASTIC agents , *RETROSPECTIVE studies , *DESCRIPTIVE statistics , *PROTEIN-tyrosine kinases , *TERMINATION of treatment , *DRUG side effects , *PATIENT safety , *EVALUATION - Abstract
Despite metastatic renal cell carcinoma (mRCC) expanded treatment options, disease progression ultimately occurs for most patients. Rechallenge may be a compelling strategy in a refractory setting. Cabozantinib is the standard of care in first and later lines of therapy, but its activity in rechallenge is unknown. This retrospective study assessed the efficacy and safety of cabozantinib rechallenge, as defined by a second exposure after an interval of ≥3 months without treatment or ≥1 other treatment line, in patients with mRCC. The primary endpoint was median progression-free survival (PFS) at rechallenge. Secondary endpoints included overall survival, objective response rate, and safety at rechallenge. We included 51 mRCC patients who received cabozantinib in a rechallenge setting between 2017 and 2022. Median age at diagnosis was 54 years, 78% were male, 90% had clear cell mRCC, and 92% had prior nephrectomy. 15 patients (29%) were rechallenged after a pause in treatment, whereas 36 (70.6%) had ≥1 other treatment lines between first cabozantinib exposure (CABO-1) and rechallenge (CABO-2). Median PFS was 15.1 months (mo, 95% Confidence interval 11.2–22.1) at CABO-1 and 14.4mo (95%CI 9.8-NR) at CABO-2. Median overall survival was 67.6mo for CABO-1 (95% CI 52.2-NR) and 27.4mo for CABO-2 (95%CI 17.2-NR); objective response rate was 70.6% for CABO-1 and 60% for CABO-2. CABO-2 PFS was higher for patients with CABO-1 PFS > 12 months, and for those who discontinued CABO-1 because of toxicity, without statistical significance. There were no unexpected adverse events. Cabozantinib rechallenge is a feasible treatment option with potential clinical benefit for mRCC patients. • This is the first study evaluating the concept of cabozantinib rechallenge to date. • The population was highly selected with heavily pretreated patients. • At rechallenge, median PFS and OS were 14.4 and 27.4 months, and ORR was 59%. • Safety did not show unexpected adverse events at rechallenge. [ABSTRACT FROM AUTHOR]
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- 2023
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23. P3.02c-065 Neutrophil-To-Lymphocyte and Other Ratios as Prognostic and Predictive Markers of Immune Checkpoint Inhibitors in Advanced NSCLC Patients: Topic: IT Biomarkers.
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Mezquita, Laura, Charrier, Melinda, Auclin, Edouard, Gion, Maria, Remon, Jordi, Planchard, David, Dupraz, Louise, Lahmar, Jihene, Gazzah, Annas, Chaput, Nathalie, and Besse, Benjamin
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- 2017
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24. P3.02c-066 HLA-A2 Status and Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients: Topic: IT Biomarkers.
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Mezquita, Laura, Charrier, Melinda, Auclin, Edouard, Dupraz, Louise, Remon, Jordi, Planchard, David, Gion, Maria, Lahmar, Jihene, Gazzah, Annas, Adam, Julien, Chaput, Nathalie, and Besse, Benjamin
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- 2017
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25. Efficacy of immune checkpoint inhibitors in microsatellite unstable/mismatch repair-deficient advanced pancreatic adenocarcinoma: an AGEO European Cohort.
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Taïeb, Julien, Sayah, Lina, Heinrich, Kathrin, Kunzmann, Volker, Boileve, Alice, Cirkel, Geert, Lonardi, Sara, Chibaudel, Benoist, Turpin, Anthony, Beller, Tamar, Hautefeuille, Vincent, Vivaldi, Caterina, Mazard, Thibault, Bauguion, Lucile, Niger, Monica, Prager, Gerald W., Coutzac, Clelia, Benedikt Westphalen, C., Auclin, Edouard, and Pilla, Lorenzo
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DRUG efficacy , *PANCREATIC tumors , *RESEARCH , *ADENOCARCINOMA , *IMMUNE checkpoint inhibitors , *DRUG tolerance , *RETROSPECTIVE studies , *DESCRIPTIVE statistics , *PROGRESSION-free survival , *OVERALL survival , *EVALUATION - Abstract
Immune checkpoint inhibitors (ICIs) improve oncological outcomes in patients with microsatellite instability-high (MSI) or mismatch repair-deficient (dMMR) advanced solid tumours. Nevertheless, based on limited published data, the outcome of patients with MSI/dMMR pancreatic ductal adenocarcinoma (PDAC) seems poorer when compared to other malignancies. This multi-institutional analysis sought to assess the efficacy and tolerability of ICIs in a large real-world cohort of patients with MSI/dMMR PDAC. We retrospectively collected data from patients with MSI/dMMR advanced PDAC treated with ICIs in 16 centers. Progression-free survival and overall survival were calculated from the start of treatment, and we report objective response and disease control rates according to RECIST V1.1. Thirty-one MSI/dMMR advanced PDAC patients were identified. Twenty-five patients received single-agent anti-PD-1 antibodies, three patients received the combination of nivolumab and ipilimumab and three patients received immunotherapy in combination with chemotherapy. Among 31 evaluable patients, 15 (48.4%) had an objective response (three complete responses and 12 partial responses), and six (19.4%) had stable disease. With a median follow-up of 18 months, the median progression-free survival (PFS) was 26.7 months and the median overall survival (OS) was not reached. Disease control rates (DCRs) among patients with only one line of prior therapy (N = 17) was 76.5%. Grade 3–4 treatment-related adverse events were not observed. This retrospective analysis suggests that ICIs are effective and well tolerated in patients with MSI/dMMR advanced PDAC. Hence, our work supports the use of PD-1 inhibition in this group of patients with high unmet medical need. • Largest series of metastatic MSI/dMMR PDAC patients treated by ICIs. • ORR and DCR were observed in 48.4% and 67.7% of the patients. • Median PFS was 26.7 months and median OS was not reached. • No significant difference was found between the different anti-PD(L)1 drugs. [ABSTRACT FROM AUTHOR]
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- 2023
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26. Gemcitabine plus platinum-based chemotherapy in combination with bevacizumab for kidney metastatic collecting duct and medullary carcinomas: Results of a prospective phase II trial (BEVABEL-GETUG/AFU24).
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Thibault, Constance, Fléchon, Aude, Albiges, Laurence, Joly, Charlotte, Barthelemy, Philippe, Gross-Goupil, Marine, Chevreau, Christine, Coquan, Elodie, Rolland, Frédéric, Laguerre, Brigitte, Gravis, Gwenaelle, Pécuchet, Nicolas, Elaidi, Réza-Thierry, Timsit, Marc-Olivier, Brihoum, Meryem, Auclin, Edouard, de Reyniès, Aurélien, Allory, Yves, and Oudard, Stéphane
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DRUG efficacy , *PATIENT aftercare , *CLINICAL trials , *CONFIDENCE intervals , *ANTINEOPLASTIC agents , *METASTASIS , *GEMCITABINE , *PLATINUM , *DUCTAL carcinoma , *KIDNEY tumors , *DESCRIPTIVE statistics , *BEVACIZUMAB , *PROGRESSION-free survival , *PATIENT safety , *LONGITUDINAL method , *OVERALL survival , *EVALUATION - Abstract
Renal medullary carcinoma (RMC) and collecting duct carcinoma (CDC) are rare entities with a poor outcome. First-line metastatic treatment is based on gemcitabine + platinum chemotherapy (GC) regimen but retrospective data suggest enhanced anti-tumour activity with the addition of bevacizumab. Therefore, we performed a prospective assessment of the safety and efficacy of GC + bevacizumab in metastatic RMC/CDC. We conducted a phase 2 open-label trial in 18 centres in France in patients with metastatic RMC/CDC and no prior systemic treatment. Patients received bevacizumab plus GC up to 6 cycles followed, for non-progressive disease, by maintenance therapy with bevacizumab until progression or unacceptable toxicity. The co-primary end-points were objective response rates (ORRs) and progression-free survival (PFS) at 6 months (ORR-6; PFS-6). PFS, overall survival (OS) and safety were secondary end-points. At interim analysis, the trial was closed due to toxicity and lack of efficacy. From 2015 to 2019, 34 of the 41 planned patients have been enroled. After a median follow-up of 25 months, ORR-6 and PFS-6 were 29.4% and 47.1%, respectively. Median OS was 11.1 months (95% confidence interval [CI]: 7.6–24.2). Seven patients (20.6%) discontinued bevacizumab because of toxicities (hypertension, proteinuria, colonic perforation). Grade 3–4 toxicities were reported in 82% patients, the most common being haematologic toxicities and hypertension. Two patients experienced grade 5 toxicity (subdural haematoma related to bevacizumab and encephalopathy of unknown origin). Our study showed no benefit for bevacizumab added to chemotherapy in metastatic RMC and CDC with higher than expected toxicity. Consequently, GC regimen remains a therapeutic option for RMC/CDC patients. • The addition of bevacizumab to chemotherapy failed to increase efficacy. • The incidence of adverse events with bevacizumab was higher than expected. • Platinum plus gemcitabine remains an treatment option for metastatic CDC/RMC. [ABSTRACT FROM AUTHOR]
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- 2023
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27. Biomarkers of response to immunotherapy in early stage non-small cell lung cancer.
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Roulleaux Dugage, Matthieu, Albarrán-Artahona, Víctor, Laguna, Juan Carlos, Chaput, Nathalie, Vignot, Stéphane, Besse, Benjamin, Mezquita, Laura, and Auclin, Edouard
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THERAPEUTIC use of monoclonal antibodies , *THERAPEUTIC use of antineoplastic agents , *LUNG cancer , *IMMUNE checkpoint inhibitors , *PROGRAMMED death-ligand 1 , *CANCER chemotherapy , *EPIDERMAL growth factor receptors , *THREONINE , *LUNG tumors , *APOPTOSIS , *CANCER patients , *SERINE , *TUMOR markers , *PROGRESSION-free survival , *COMBINED modality therapy , *IMMUNOTHERAPY - Abstract
Immunotherapy with immune-checkpoint inhibitors (ICIs) targeting programmed cell death 1 or programmed death-ligand 1 has revolutionised the treatment of advanced non-small cell lung cancer (NSCLC) and has been investigated in early NSCLC, alone or in combination with chemotherapy, anti-CTLA-4 antibodies and radiotherapy. Although more mature data are needed before setting a change of paradigm in early stages, reports of pathological response rates and disease-free survival are promising, especially with neoadjuvant multimodality approaches. Nevertheless, major pathological response rates for neoadjuvant anti-PD-(L)1 monotherapy rarely exceed 40%, and biomarkers for characterising patients who may benefit the most from ICIs are lacking. These biomarkers have a distinct value from the metastatic setting, with highly different tumour biologies. Among the most investigated so far in this context, programmed death-ligand 1 expression and, to a lesser extent, tumour mutational burden seem to correlate better with higher pathological response rates and survival. Epidermal growth factor receptor , Serine/Threonine Kinase 11 and Kelch-like ECH-associated protein 1 mutations rise as essential determinations for the treatment selection in early-stage NSCLC. Emerging and promising approaches comprise evaluation of blood-based ratios, microbiota, and baseline intratumoural TCR clonality. Circulating tumour DNA will be of great help in the near future when selecting best candidates for adjuvant ICIs, monitoring the tumour response to the neoadjuvant treatment in order to improve the rates of complete resections in the early stage. • Immune-checkpoint inhibitors (ICIs)are becoming a standard in early non-small cell lung cancer but do not benefit all patients. • Programmed death-ligand 1 expression and tumour mutational burden are the better-documented biomarkers. • Patients with epidermal growth factor receptor , Serine/Threonine Kinase 11 or Kelch-like ECH-associated protein 1 alterations yield poor benefit from ICIs. • Emerging biomarkers include TCR clonality, microbiota and blood-based ratios. • Circulating tumour DNA is a reliable tool to evaluate disease burden following surgery or ICIs. [ABSTRACT FROM AUTHOR]
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- 2023
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28. A multicenter study evaluating efficacy of immune checkpoint inhibitors in advanced non-colorectal digestive cancers with microsatellite instability.
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Moreau, Mathilde, Alouani, Emily, Flecchia, Clémence, Falcoz, Antoine, Gallois, Claire, Auclin, Edouard, André, Thierry, Cohen, Romain, Hollebecque, Antoine, Turpin, Anthony, Pernot, Simon, Masson, Thérèse, Di Fiore, Frederic, Dutherge, Marie, Mazard, Thibault, Hautefeuille, Vincent, Van Laethem, Jean-Luc, De la Fouchardière, Christelle, Perkins, Géraldine, and Ben-Abdelghani, Meher
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STOMACH tumors , *IMMUNOTHERAPY , *DNA , *RETROSPECTIVE studies , *MULTIVARIATE analysis , *DESCRIPTIVE statistics , *IMMUNE checkpoint inhibitors , *CANCER chemotherapy , *METASTASIS , *DRUG efficacy , *RESEARCH , *INTESTINAL tumors , *TUMORS , *DIGESTIVE organs , *PATHOGENESIS , *PROGRESSION-free survival , *EVALUATION - Abstract
One randomized phase III trial comparing chemotherapy (CT) with immune checkpoint inhibitors (ICI) has demonstrated significant efficacy of ICI in deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer. However, few studies have compared ICI with CT in other advanced dMMR/MSI-H digestive tumors. In this multicenter study, we included patients with advanced dMMR/MSI-H non-colorectal digestive tumors treated with chemotherapy and/or ICIs. Patients were divided retrospectively into two groups, a CT group and an immunotherapy (IO) group. The primary endpoint was progression-free survival (PFS). A propensity score approach using the inverse probability of treatment weighting (IPTW) method was applied to deal with potential differences between the two groups. 133 patients (45.1/27.1/27.8% with gastric/small bowel/other carcinomas) were included. The majority of patients received ICI in 1st (29.1%) or 2nd line (44.4%). The 24-month PFS rates were 7.9% in the CT group and 71.2% in the IO group. Using the IPTW method, IO treatment was associated with better PFS (HR=0.227; 95% CI 0.147–0.351; p < 0.0001). The overall response rate was 26.3% in the CT group versus 60.7% in the IO group (p < 0.001) with prolonged duration of disease control in the IO group (p < 0.001). In multivariable analysis, predictive factors of PFS for patients treated with IO were good performance status, absence of liver metastasis and prior primary tumor resection, whereas no association was found for the site of the primary tumor. In the absence of randomized trials, our study highlights the superior efficacy of ICI compared with standard-of-care therapy in patients with unresectable or metastatic dMMR/MSI-H non-colorectal digestive cancer, regardless of tumor type, with acceptable toxicity. • Immunotherapy (IO) has high efficacy in mismatch-repair deficient (dMMR) tumors. • No trial compared chemotherapy (CT) and ICI in non-colorectal dMMR digestive tumors. • ICI has higher progression-free survival, regardless primary tumor site. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Pleural effusion is a negative prognostic factor for immunotherapy in patients with non-small cell lung cancer (NSCLC): The pluie study.
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Epaillard, Nicolas, Benitez, Jose Carlos, Gorria, Teresa, Fabre, Elizabeth, Riudavets, Mariona, Reyes, Roxana, Planchard, David, Oudard, Stéphane, Viñolas, Nuria, Reguart, Noemi, Besse, Benjamin, Mezquita, Laura, and Auclin, Edouard
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NON-small-cell lung carcinoma , *IMMUNE checkpoint inhibitors , *TREATMENT effectiveness , *CANCER prognosis , *OVERALL survival , *METASTASIS , *PLEURAL effusions - Abstract
• Pleural effusion (PE) is associated with worse immunotherapy outcomes in NSCLC. • This negative impact was also observed in patients with ≥50 % PD-L1 tumors. • In patients with PE, combinations strategies should be explored. Pleural effusion (PE) is a common metastatic site of NSCLC, associated with poor outcomes. As very few data are available about immune checkpoint inhibitors (ICI) and PE, we aimed to assess the clinical outcome of PE in NSCLC treated with ICI. Multicenter international retrospective study of patients with metastatic NSCLC treated with ICI, between 2012 and 2019. Stratification according to the presence of PE at ICI baseline or appearance under ICI treatment (PE group) versus no history of PE (non-PE group). Primary endpoints were overall survival (OS) and early death rate (EDR, OS ≤ 3 months). A total of 538 patients were included: 196 in the PE group and 342 in the non-PE group. In the PE group, median age was 64, 31.6 % were female, 77.6 % had non-squamous histology, PD-L1 was ≥50 % in 38.6 % of cases (95 missing). PE was more likely associated with >2 metastatic sites (70.4 % vs. 50 %) and worse performance status (PS ≥ 2, 30.8 % vs 23.1 %). Globally, the overall median OS was 9.7 months [95 %CI: 8.1–11.8]; 6.3 [95 % CI: 4.0–8.6] in PE vs. 11.4 [95 %CI: 9.7–13.8] in the non-PE respectively, P = 0.002. Overall the EDR was 31.4 %; higher in the PE group (38.3 % vs. 27.5 %; OR 1.63, 95 %CI: 1.13−2.37, P = 0.01). In the PE PD-L1≥50 % group, EDR was 33.3 %. In multivariate analysis, after adjustment on PS, liver/intracranial/bone metastasis, ICI line and dNLR, PE remained an independent prognostic factor for OS [HR: 1.38, 95 %CI: 1.09–1.74, P = 0.007]. In the PE group, PE appeared under ICI for 31 patients (16.4 %). We observed lower EDR in this group compared to patients whom PE was already present (29.0 % vs 40.5 %, P = 0.2). PE is associated with worse immunotherapy outcomes in NSCLC treated with ICI, including in patients with ≥50 % PD-L1 tumors. Thus, in these patients, combination strategies should be explored. [ABSTRACT FROM AUTHOR]
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- 2021
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30. Tumour-infiltrating lymphocyte density is associated with favourable outcome in patients with advanced non–small cell lung cancer treated with immunotherapy.
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Gataa, Ithar, Mezquita, Laura, Rossoni, Caroline, Auclin, Edouard, Kossai, Myriam, Aboubakar, Frank, Le Moulec, Sylvestre, Massé, Julie, Masson, Morgane, Radosevic-Robin, Nina, Alemany, Pierre, Rouanne, Mathieu, Bluthgen, Virginia, Hendriks, Lizza, Caramella, Caroline, Gazzah, Anas, Planchard, David, Pignon, Jean-Pierre, Besse, Benjamin, and Adam, Julien
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LUNG cancer , *RESEARCH , *ADENOCARCINOMA , *IMMUNE checkpoint inhibitors , *CONFIDENCE intervals , *CANCER chemotherapy , *MEDICAL cooperation , *RETROSPECTIVE studies , *LYMPHOCYTES , *TREATMENT effectiveness , *CANCER patients , *DESCRIPTIVE statistics , *IMMUNOTHERAPY - Abstract
The established role of morphological evaluation of tumour-infiltrating lymphocytes (TILs) with immune checkpoint inhibitors (ICIs) in non–small cell lung cancer (NSCLC) is unknown. We aimed to determine TIL association with the outcome for ICIs and for chemotherapy in advanced NSCLC. This is a multicenter retrospective study of a nivolumab cohort of 221 patients treated between November 2012 and February 2017 and a chemotherapy cohort of 189 patients treated between June 2009 and October 2016. Patients with available tissue for stromal TIL evaluation were analysed. The presence of a high TIL count (high-TIL) was defined as ≥10% density. The primary end-point was overall survival (OS). Among the nivolumab cohort, 64% were male, with median age of 63 years, 82.3% were smokers, 77% had performance status ≤1 and 63% had adenocarcinoma histology. High-TIL was observed in 22% patients and associated with OS (hazard ratio [HR] 0.48; 95% confidence interval [95% CI]: 0.28–0.81) and progression-free survival [PFS] (HR = 0.40; 95% CI: 0.25–0.64). Median PFS was 13.0 months (95% CI: 5.0–not reached) with high-TIL versus 2.2 months (95% CI: 1.7–3.0) with the presence of a low TIL count (low-TIL). Median OS for high-TIL was not reached (95% CI: 12.2–not reached) versus 8.4 months (95% CI: 5.0–11.6) in the low-TIL group. High-TIL was associated with the overall response rate (ORR) and disease control rate (DCR) (both, P <.0001). Among the chemotherapy cohort, 69% were male, 89% were smokers, 86% had performance status ≤1 and 90% had adenocarcinoma histology. High-TIL was seen in 37%. Median PFS and OS were 5.7 months (95% CI: 4.9–6.7) and 11.7 months (95% CI: 9.3–13.0), respectively, with no association with TILs. High-TIL was associated with favourable outcomes in a real-world immunotherapy cohort of patients with NSCLC, but not with chemotherapy, suggesting that TILs may be useful in selecting patients for immunotherapy. • High–tumour infiltrating lymphocyte (TIL) density was associated with immunotherapy benefit in non–small cell lung cancer (NSCLC) patients. • No correlation with outcome was observed in chemotherapy-treated patients with NSCLC. • TILs may be useful in selecting patients for immunotherapy. [ABSTRACT FROM AUTHOR]
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- 2021
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31. Evaluation of two nutritional scores' association with systemic treatment toxicity and survival in metastatic colorectal cancer: an AGEO prospective multicentre study.
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Gallois, Claire, Artru, Pascal, Lièvre, Astrid, Auclin, Edouard, Lecomte, Thierry, Locher, Christophe, Marthey, Lysiane, Zaimi, Yosra, Faroux, Roger, Pernot, Simon, Barret, Maximilien, and Taieb, Julien
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MALNUTRITION , *CANCER chemotherapy , *CANCER patients , *COLON tumors , *CONFIDENCE intervals , *DRUG toxicity , *LONGITUDINAL method , *RESEARCH methodology , *MEDICAL cooperation , *METASTASIS , *NUTRITIONAL assessment , *RESEARCH , *SURVIVAL analysis (Biometry) , *TREATMENT effectiveness , *RETROSPECTIVE studies , *RESEARCH methodology evaluation , *DESCRIPTIVE statistics , *DISEASE complications ,RECTUM tumors - Abstract
The Patient-Generated Subjective Global Assessment (PG-SGA) is currently the standard nutritional assessment tool for patients with cancer. In a retrospective assessment of a prospective cohort, we showed that the Nutritional Risk Index (NRI) seemed to be associated with treatment toxicity and survival in patients with metastatic colorectal cancer (mCRC). The objective of this study was to compare these two nutritional tools (PG-SGA and NRI) on their correlation with chemotherapy-related toxicity and survival in non–pre-treated patients with mCRC. This prospective multicentre observational study enrolled non–pre-treated patients with mCRC. PG-SGA and NRI were performed at the onset of first-line chemotherapy. Treatment-related toxicities were registered according to National Cancer Institute Common Toxicity Criteria Adverse Event version 4.0. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment. A total of 168 patients were included from eight French centres. Patients were considered malnourished in 41% of cases according to PG-SGA and 56% of cases according to the NRI. In multivariate analysis, malnutrition according to PG-SGA was significantly associated with chemotherapy-related grade ≥2 clinical toxicities (odds ratio: 3.7; 95% confidence interval [CI]: 1.7–8.4; p = 0.001) and OS (hazard ratio [HR]: 2.6; 95% CI: 1.3–5.3; p = 0.006), but not with PFS (HR: 1.5; 95% CI: 0.8–2.6; p = 0.2). Conversely, malnutrition according to the NRI was not significantly associated with these tolerance and efficacy parameters. Although more complex to perform in daily oncology practice, the PG-SGA score appears to be the best nutritional assessment tool because of its strong association with clinically relevant oncological outcomes such as OS and treatment-related toxicities in patients with mCRC. • In colorectal cancer (CRC), malnutrition is associated with chemotherapy-related toxicities. • In CRC, malnutrition is associated with decreased overall survival. • Patient-Generated Subjective Global Assessment should now be the standard nutritional assessment for patients with metastatic CRC. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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