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1. Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma

Author

Bhave, P, Ahmed, T, Lo, SN, Shoushtari, A, Zaremba, A, Versluis, JM, Mangana, J, Weichenthal, M, Si, L, Lesimple, T, Robert, C, Trojanello, C, Wicky, A, Heywood, R, Tran, L, Batty, K, Dimitriou, F, Stansfeld, A, Allayous, C, Schwarze, JK, Mooradian, MJ, Klein, O, Mehmi, I, Roberts-Thomson, R, Maurichi, A, Yeoh, H-L, Khattak, A, Zimmer, L, Blank, CU, Ramelyte, E, Kaehler, KC, Roy, S, Ascierto, PA, Michielin, O, Lorigan, PC, Johnson, DB, Plummer, R, Lebbe, C, Neyns, B, Sullivan, R, Hamid, O, Santinami, M, McArthur, GA, Haydon, AM, Long, G, Menzies, AM, Carlino, MS, Bhave, P, Ahmed, T, Lo, SN, Shoushtari, A, Zaremba, A, Versluis, JM, Mangana, J, Weichenthal, M, Si, L, Lesimple, T, Robert, C, Trojanello, C, Wicky, A, Heywood, R, Tran, L, Batty, K, Dimitriou, F, Stansfeld, A, Allayous, C, Schwarze, JK, Mooradian, MJ, Klein, O, Mehmi, I, Roberts-Thomson, R, Maurichi, A, Yeoh, H-L, Khattak, A, Zimmer, L, Blank, CU, Ramelyte, E, Kaehler, KC, Roy, S, Ascierto, PA, Michielin, O, Lorigan, PC, Johnson, DB, Plummer, R, Lebbe, C, Neyns, B, Sullivan, R, Hamid, O, Santinami, M, McArthur, GA, Haydon, AM, Long, G, Menzies, AM, and Carlino, MS

Abstract

BACKGROUND: Acral melanoma is a rare melanoma subtype with poor prognosis. Importantly, these patients were not identified as a specific subgroup in the landmark melanoma trials involving ipilimumab and the anti-programmed cell death protein-1 (PD-1) agents nivolumab and pembrolizumab. There is therefore an absence of prospective clinical trial evidence regarding the efficacy of checkpoint inhibitors (CPIs) in this population. Acral melanoma has lower tumor mutation burden (TMB) than other cutaneous sites, and primary site is associated with differences in TMB. However the impact of this on the effectiveness of immune CPIs is unknown. We examined the efficacy of CPIs in acral melanoma, including by primary site. METHODS: Patients with unresectable stage III/IV acral melanoma treated with CPI (anti-PD-1 and/or ipilimumab) were studied. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was objective response rate (ORR); secondary outcomes were progression-free survival (PFS) and overall survival (OS). RESULTS: In total, 325 patients were included: 234 (72%) plantar, 69 (21%) subungual and 22 (7%) palmar primary sites. First CPI included: 184 (57%) anti-PD-1, 59 (18%) anti-PD-1/ipilimumab combination and 82 (25%) ipilimumab. ORR was significantly higher with initial anti-PD-1/ipilimumab compared with anti-PD-1 (43% vs 26%, HR 2.14, p=0.0004) and significantly lower with ipilimumab (15% vs 26%, HR 0.49, p=0.0016). Landmark PFS at 1 year was highest for anti-PD-1/ipilimumab at 34% (95% CI 24% to 49%), compared with 26% (95% CI 20% to 33%) with anti-PD-1 and 10% (95% CI 5% to 19%) with ipilimumab. Despite a trend for increased PFS, anti-PD-1/ipilimumab combination did not significantly improve PFS (HR 0.85, p=0.35) or OS over anti-PD-1 (HR 1.30, p=0.16), potentially due to subsequent therapies and high rates of acquired resistance. No outcome differences were found between primary sites. CONCLUSION: While the ORR to anti-PD-1/ipilimumab wa

Published
2022

2. Impact of COVID-19 outbreak on cancer immunotherapy in Italy: A survey of young oncologists

Author

Sara Parola, Diletta Cavallero, Pietro De Placido, Rossella Di Franco, Francesca Zacchi, Giacomo Cartenì, Sabino De Placido, Claudia von Arx, Alice Rossi, Fernanda Picozzi, Pasquale Rescigno, Laura Attademo, Giovannella Palmieri, Carminia Maria Della Corte, Fabiana Vitiello, Anna Russo, Lucia Nappi, Michele Aieta, Alessia Mennitto, Fabiana Napolitano, Marco Messina, Giuseppe Buono, Valeria Merz, Marco De Felice, Stefano De Falco, Immacolata Paciolla, Irene De Santo, Dario Trapani, Antonio M. Grimaldi, Paolo Tarantino, Alessandro Morabito, Tortora Vincenzo, Stefano Pepe, Giuseppe Palmieri, Antonietta Fabbrocini, Diana Giannarelli, Alfonso De Stefano, Sabrina Vari, Cesare Gridelli, Vittorio Riccio, Angelica Petrillo, Martina Pagliuca, Giuseppe Calderoni, Margaret Ottaviano, Vincenza Conteduca, Michela Lia, Giuseppe Santabarbara, Ester Simeone, Valentina Borzillo, Francesca Caputo, Mario Rosanova, Marcello Curvietto, Pasquale Assalone, Brigitta Mucci, Raffaele Conca, Vito Vanella, Francovito Piantedosi, Vincenzo Montesarchio, Erica Pietroluongo, Lucia Festino, Federica Tomei, Vincenzo Di Lauro, Bruno Daniele, Caterina Vivaldi, Andrea Zivi, Veronica Prati, Pasqualina Giordano, Luisa Piccin, Francesco Bloise, Massimiliano Spada, Jole Ventriglia, Davide Bosso, Alessandro Marco Minisini, Massimiliano Salati, Monica Milano, Carlo Messina, Valentina Massa, Mario Giuliano, Claudia Trojanello, Antonella Lucia Marretta, Fortunato Ciardiello, Antonio Avallone, Marianna Tortora, Ilaria Zampiva, Alessia Cavo, Floriana Morgillo, Andrea Sbrana, Piera Federico, Maria Grazia Vitale, Sandro Pignata, Antonia Silvestri, Paola Taveggia, Sara Merler, Paolo A. Ascierto, Michelino De Laurentiis, Ottaviano, Margaret, Curvietto, Marcello, Rescigno, Pasquale, Tortora, Marianna, Palmieri, Giovannella, Giannarelli, Diana, Aieta, Michele, Assalone, Pasquale, Attademo, Laura, Avallone, Antonio, Bloise, Francesco, Bosso, Davide, Borzillo, Valentina, Buono, Giuseppe, Calderoni, Giuseppe, Caputo, Francesca, Cartenì, Giacomo, Cavallero, Diletta, Cavo, Alessia, Ciardiello, Fortunato, Conca, Raffaele, Conteduca, Vincenza, De Falco, Stefano, De Felice, Marco, De Laurentiis, Michelino, De Placido, Pietro, De Placido, Sabino, De Santo, Irene, De Stefano, Alfonso, Della Corte, Carminia Maria, Di Franco, Rossella, Di Lauro, Vincenzo, Fabbrocini, Antonietta, Federico, Piera, Festino, Lucia, Giordano, Pasqualina, Giuliano, Mario, Gridelli, Cesare, Grimaldi, Antonio Maria, Lia, Michela, Marretta, Antonella Lucia, Massa, Valentina, Mennitto, Alessia, Merler, Sara, Merz, Valeria, Messina, Carlo, Messina, Marco, Milano, Monica, Minisini, Alessandro Marco, Montesarchio, Vincenzo, Morabito, Alessandro, Morgillo, Floriana, Mucci, Brigitta, Nappi, Lucia, Napolitano, Fabiana, Paciolla, Immacolata, Pagliuca, Martina, Palmieri, Giuseppe, Parola, Sara, Pepe, Stefano, Petrillo, Angelica, Piantedosi, Francovito, Piccin, Luisa, Picozzi, Fernanda, Pietroluongo, Erica, Pignata, Sandro, Prati, Veronica, Riccio, Vittorio, Rosanova, Mario, Rossi, Alice, Russo, Anna, Salati, Massimiliano, Santabarbara, Giuseppe, Sbrana, Andrea, Simeone, Ester, Silvestri, Antonia, Spada, Massimiliano, Tarantino, Paolo, Taveggia, Paola, Tomei, Federica, Vincenzo, Tortora, Trapani, Dario, Trojanello, Claudia, Vanella, Vito, Vari, Sabrina, Ventriglia, Jole, Vitale, Maria Grazia, Vitiello, Fabiana, Vivaldi, Caterina, von Arx, Claudia, Zacchi, Francesca, Zampiva, Ilaria, Zivi, Andrea, Daniele, Bruno, Ascierto, Paolo Antonio, Ottaviano, M., Curvietto, M., Rescigno, P., Tortora, M., Palmieri, G., Giannarelli, D., Aieta, M., Assalone, P., Attademo, L., Avallone, A., Bloise, F., Bosso, D., Borzillo, V., Buono, G., Calderoni, G., Caputo, F., Carteni, G., Cavallero, D., Cavo, A., Ciardiello, F., Conca, R., Conteduca, V., De Falco, S., De Felice, M., De Laurentiis, M., De Placido, P., De Placido, S., De Santo, I., De Stefano, A., Della Corte, C. M., Di Franco, R., Di Lauro, V., Fabbrocini, A., Federico, P., Festino, L., Giordano, P., Giuliano, M., Gridelli, C., Grimaldi, A. M., Lia, M., Marretta, A. L., Massa, V., Mennitto, A., Merler, S., Merz, V., Messina, C., Messina, M., Milano, M., Minisini, A. M., Montesarchio, V., Morabito, A., Morgillo, F., Mucci, B., Nappi, L., Napolitano, F., Paciolla, I., Pagliuca, M., Parola, S., Pepe, S., Petrillo, A., Piantedosi, F., Piccin, L., Picozzi, F., Pietroluongo, E., Pignata, S., Prati, V., Riccio, V., Rosanova, M., Rossi, A., Russo, A., Salati, M., Santabarbara, G., Sbrana, A., Simeone, E., Silvestri, A., Spada, M., Tarantino, P., Taveggia, P., Tomei, F., Vincenzo, T., Trapani, D., Trojanello, C., Vanella, V., Vari, S., Ventriglia, J., Vitale, M. G., Vitiello, F., Vivaldi, C., Von Arx, C., Zacchi, F., Zampiva, I., Zivi, A., Daniele, B., and Ascierto, P. A.

Subjects
Male, Cancer Research, Immune checkpoint inhibitors, Programmed Cell Death 1 Receptor, Practice Patterns, Medical Oncology, B7-H1 Antigen, Antineoplastic Agents, Immunological, 0302 clinical medicine, Drug Prescription, Neoplasms, Surveys and Questionnaires, Pandemic, Prevalence, Surveys and Questionnaire, Infection control, Immunology and Allergy, CTLA-4 Antigen, 030212 general & internal medicine, Viral, Practice Patterns, Physicians', RC254-282, Clinical/Translational Cancer Immunotherapy, Oncologists, Geography, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, antineoplastic protocols, Immunological, Oncology, Italy, 030220 oncology & carcinogenesis, Molecular Medicine, Female, immunotherapy, Coronavirus Infections, Human, healthcare economics and organizations, Adult, Telemedicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Immunology, Antineoplastic Agents, lung neoplasms, Drug Prescriptions, Time-to-Treatment, 03 medical and health sciences, Betacoronavirus, medicine, melanoma, COVID-19, Humans, Infection Control, Pandemics, SARS-CoV-2, Medical prescription, Pharmacology, Physicians', Betacoronaviru, Coronavirus Infection, Cancer, Outbreak, Pneumonia, medicine.disease, lung neoplasm, antineoplastic protocol, Family medicine, healthcare economics and organization, Oncologist, Neoplasm
Abstract

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region.MethodsThis survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2–positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher’s exact tests for dichotomous answers and χ2 test for trends relative to the questions with 3 or more options.ResultsThis is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2–positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients’ planned treatment approach). The results from responders in Campania did not differ significantly from the national ones.ConclusionOur study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.

Published
2020

3. Long-term outcomes and persistent toxicities following BRAF/MEK inhibitor therapy for advanced melanoma.

Author

Goodman RS, Di Guardo L, Maurichi A, Kirwin B, Khattak A, Vanella V, Lee J, Lawless A, Czapla J, Spagnoletti A, Ambrosini M, Livingstone E, Long GV, Sullivan RJ, Carlino MS, Atkinson V, Trojanello C, Ascierto PA, Schadendorf D, Warburton L, Menzies AM, Santinami M, and Johnson DB

Subjects
Humans, Proto-Oncogene Proteins B-raf genetics, Cohort Studies, Antineoplastic Combined Chemotherapy Protocols adverse effects, Protein Kinase Inhibitors adverse effects, Mitogen-Activated Protein Kinase Kinases, Mutation, Skin Neoplasms pathology, Melanoma pathology
Abstract

Background: Recent studies have shown that approximately 20% of patients have 4-5 year progression free survival (PFS) on BRAF/MEK inhibitors. The long-term safety and efficacy in these patients with more durable responses have not been studied., Methods: This retrospective multicenter cohort study assessed response, progression, and adverse events in patients from eight institutions in four countries with >4-year PFS following BRAF/MEK inhibitors., Results: Among 146 patients, 112 (76.7%) remained progression-free at median follow-up of 7.8 years from treatment start; 131 (89.7%) were alive. Among progressors (n = 34), 21 (62%) were on treatment at progression. Among those who discontinued treatment for reasons other than progression (toxicity, preference, etc.) (n = 68, with median 49 months treatment duration), 13 (19%) progressed (median 15.3 months from treatment cessation to progression). Surgery or radiation for single-organ progression resulted in durable benefit in 11 of 22 patients (50%). Subsequent systemic therapy included immune therapy (24% responded) and BRAF/MEK rechallenge (56% responded). Thirteen (8.9%) patients had ongoing toxicities at last follow-up, 10 (77%) of which remained on active treatment; all cardiac adverse events had resolved (n = 9). Twenty-four (16.4%) patients developed any new primary cancer, and 28 (19%) patients experienced other major health events., Conclusions: Over 75% of patients with 4-year PFS from BRAF/MEK inhibitors had continued durable antitumor responses after nearly 8-year median follow-up, with similar results in patients who discontinued therapy for reasons other than progression. Long-term toxicities were uncommon and low-grade. These findings highlight the often-favourable outcomes in patients with extended benefit from BRAF/MEK inhibitors., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MSC has served on advisory boards or as a consultant for Amgen, BMS, Eisai, Ideaya, MSD, Nektar, Novartis, Oncosec, Pierre-Fabre, Qbiotics, Regeneron, Roche, Merck and Sanofi, and received honoraria from BMS, MSD, and Novartis. AMM has served on advisory boards for BMS, MSD, Novartis, Roche, Pierre-Fabre and QBiotics. EL served as consultant and/or has received honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre-Fabre, Sanofi, Sunpharma, Takeda and travel support from Bristol-Myers Squibb, Pierre- Fabre, Sunpharma and Novartis, outside the submitted work. RJS has served on advisory boards or as a consultant for BMS, Marengo, Merck, Novartis, Pfizer, and Replimune. GVL is consultant advisor for Agenus, Amgen, Array Biopharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics USA, Merck Sharpe & Dohme, Novartis, OncoSec, PHMR Ltd, Pierre Fabre, Provectus, Qbiotics, Regeneron. DS has served on advisory boards for BMS, Immunocore, MSD, Neracare, Novartis, Pfizer, Philogen, Pierre Fabre, and Sanofi/Regeneron. LW has served on advisory boards for BMS, MSD and Novartis. DBJ has served on advisory boards or as a consultant for BMS, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko, has received research funding from BMS and Incyte, and has patents pending for use of MHC-II as a biomarker for immune checkpoint inhibitor response, and abatacept as treatment for immune-related adverse events. All remaining authors have declared no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Published
2023
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4. Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma.

Author

Bhave P, Ahmed T, Lo SN, Shoushtari A, Zaremba A, Versluis JM, Mangana J, Weichenthal M, Si L, Lesimple T, Robert C, Trojanello C, Wicky A, Heywood R, Tran L, Batty K, Dimitriou F, Stansfeld A, Allayous C, Schwarze JK, Mooradian MJ, Klein O, Mehmi I, Roberts-Thomson R, Maurichi A, Yeoh HL, Khattak A, Zimmer L, Blank CU, Ramelyte E, Kähler KC, Roy S, Ascierto PA, Michielin O, Lorigan PC, Johnson DB, Plummer R, Lebbe C, Neyns B, Sullivan R, Hamid O, Santinami M, McArthur GA, Haydon AM, Long GV, Menzies AM, and Carlino MS

Subjects
Humans, Ipilimumab pharmacology, Ipilimumab therapeutic use, Prospective Studies, Retrospective Studies, Skin Neoplasms, Melanoma, Cutaneous Malignant, Melanoma drug therapy
Abstract

Background: Acral melanoma is a rare melanoma subtype with poor prognosis. Importantly, these patients were not identified as a specific subgroup in the landmark melanoma trials involving ipilimumab and the anti-programmed cell death protein-1 (PD-1) agents nivolumab and pembrolizumab. There is therefore an absence of prospective clinical trial evidence regarding the efficacy of checkpoint inhibitors (CPIs) in this population. Acral melanoma has lower tumor mutation burden (TMB) than other cutaneous sites, and primary site is associated with differences in TMB. However the impact of this on the effectiveness of immune CPIs is unknown. We examined the efficacy of CPIs in acral melanoma, including by primary site., Methods: Patients with unresectable stage III/IV acral melanoma treated with CPI (anti-PD-1 and/or ipilimumab) were studied. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was objective response rate (ORR); secondary outcomes were progression-free survival (PFS) and overall survival (OS)., Results: In total, 325 patients were included: 234 (72%) plantar, 69 (21%) subungual and 22 (7%) palmar primary sites. First CPI included: 184 (57%) anti-PD-1, 59 (18%) anti-PD-1/ipilimumab combination and 82 (25%) ipilimumab. ORR was significantly higher with initial anti-PD-1/ipilimumab compared with anti-PD-1 (43% vs 26%, HR 2.14, p=0.0004) and significantly lower with ipilimumab (15% vs 26%, HR 0.49, p=0.0016). Landmark PFS at 1 year was highest for anti-PD-1/ipilimumab at 34% (95% CI 24% to 49%), compared with 26% (95% CI 20% to 33%) with anti-PD-1 and 10% (95% CI 5% to 19%) with ipilimumab. Despite a trend for increased PFS, anti-PD-1/ipilimumab combination did not significantly improve PFS (HR 0.85, p=0.35) or OS over anti-PD-1 (HR 1.30, p=0.16), potentially due to subsequent therapies and high rates of acquired resistance. No outcome differences were found between primary sites., Conclusion: While the ORR to anti-PD-1/ipilimumab was significantly higher than anti-PD-1 and PFS numerically higher, in this retrospective cohort this benefit did not translate to improved OS. Future trials should specifically include patients with acral melanoma, to help determine the optimal management of this important melanoma subtype., Competing Interests: Competing interests: PB: sponsorship: Bristol Myers Squibb, MSD, Novartis; paid speaker: Novartis. AS: advisory board: Bristol Myers Squibb, Immunocore, Novartis, Castle Biosciences; trial support to institution: Bristol Myers Squibb, Imunocore, Xcovery, Polaris, Novartis, Pfizer, Checkmate Pharmaceuticals, Foghorn Therapeautics. AZ: travel support: Novartis, Sanofi Grenzyme, Sun Pharma, Bristol Myers Squibb. JM: consultant advisor: Merck/Pfizer, Merck Sharp & Dohme, Amgen, Novartis, Sanofi, Bristol Myers Squibb and Pierre Fabre; travel support: Ultrasun, L’Oreal, Merck Sharp & Dohme, Bristol Myers Squibb, Pierre Fabre. MW: grants, personal fees, non-financial support and other: Novartis, BMS, Merck/MSD; personal fees, and other: Merck Serono, Amgen, Sanofi/Regeneron, Pierre Fabre, Roche, Takeda, Medac. LS: honoraria: MSD, Roche, Novartis, Shanghai Junshi Biosciences, Oriengene. TL: consultant: MSD, Novartis, Pierre Fabre. CR: consultant for Novartis, BMS, Merck, MSD, Sanofi, Pierre Fabre, AstraZeneca, Roche, and scientic founder of Aglaia Therapeutics CA: Travel accommodations-Meetings: Roche, Bristol Myers Squibb, Amgen. JKS: sponsorship: MSD, Amgen; honoraria: Novartis. MJM: consultant advisor: AstraZeneca, Nektar Therapeutics, Catalyst Pharmaceuticals Immunia, Istari Oncology; paid speaker: Bristol Myers Squibb. RR-T: advisory board fees: Novartis, Bristol Myer Squibb, Merck, Sharp and Dohme, Pfizer; honoraria: Bristol Myer Squibb, Roche, AstraZeneca, Merck Sharp and Dohme, Novartis. AM: honoraria from Novartis. LZ: consultant and/or honoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, Sunpharma; travel support: Amgen, Merck Sharp & Dohme, BristolMyers Squibb, Pierre Fabre, Sanofi, Sunpharma, Novartis. CB (all paid to the institute except TRV): advisory board: Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, GenMab, Pierre Fabre, Third Rock Ventures; research funding: Bristol Myers Squibb, Novartis, NanoString; stockownership & co-founder: Immagene BV. ER: consultant advisor or paid speaker: Sanofi, Amgen, BMS. KK: consultant or/and honoraria: Amgen, Roche, Bristol Myers Squibb, Merck Sharp and Dohme, Pierre Fabre, Novartis; travel support: Amgen, Merck Sharp and Dohme, Bristol Myers Squibb, Amgen, Pierre Fabre, Medac, Novartis. PAA: consultant/advisory role: Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos; research funding: Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. OM: consulting/advisory roles: Bristol Myers Squibb, MSD, Roche, Novartis, Amgen, Pierre Fabre, Neracare; research grants: Bristol Myers Squibb, MSD, Amgen. PCL: Consultant advisor or paid speaker: Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Amgen, Nektar. Research funding: Bristol Myers Squibb, Pierre Fabre. DBJ: advisory boards/consultant: BMS, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, and Targovax. Research funding: BMS and Incyte. RP: advisory boards: Pierre Faber, Bayer, Novartis, Biosceptre, Bristol Myers Squibb, Cybrexa, Ellipses, CV6 Therapeutics, Astex Therapeutics, Medivir, GammaDelta Therapeutics, Sanofi Aventis; paid speaker: AstraZeneca, Novartis, Bayer, Tesaro, Bristol Myers Squibb. CL: BMS: Research grant, Honoraria, Consultancy, Speakers bureau, Travel accommodations, Meetings, Advisory role, advisory board. MSD: Honoraria, Consultancy, Advisory role, advisory board, Travel accommodations-Meetings. Novartis: Honoraria, Consultancy, Speakers bureau, Advisory role, advisory board. Amgen: Honoraria, Consultancy, Speakers bureau, advisory board. Roche: Research grant, Honoraria, Consultancy, Speakers bureau, Advisory role, advisory board. Avantis Medical Systems: Board. Pierre-Fabre/Pfizer/Incyte: Honoraria. BN: Personal financial compensation from Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Amgen and AstraZeneca for public speaking, consultancy and participation in advisory board meetings. My institution (UZ Brussel) received funding related to research projects conducted by my academic research team from Pfizer, Novartis, Roche, and Merck-Serono. RJS: Consultant: AstraZeneca, Bristol Myers Squibb, Eisai, Iovance, Merck, Novartis, Pfizer; research funding: Merck. OH: consultant advisor: Aduro, Akeso, Amgen, Beigene, Bioatla, BMS, Roche Genentech, GSK, Immunocore, Idera, Incyte, Janssen, Merck, Nextcure, Novartis, Pfizer, Sanofi/Regeneron, Seattle Genetics, Tempus, Zelluna; speaker bureau: BMS, Novartis, Pfizer, Sanofi/Regeneron; contracted research (for institution): Arcus, Aduro, Akeso, Amgen, Bioatla, BMS, CytomX, Exelixis, Roche Genentech, GSK, Immunocore, Idera, Incyte, Iovance, Merck, Moderna, Merck-Serono, NextCure, Novartis, Pfizer, Sanofi/Regeneron, Seattle Genetics, Torque, Zelluna. GAM: reimbursement of trials costs to the Peter MacCallum Cancer Centre: Array/Pfizer Roche/Genetech; non-reimbursed advisor: Novartis, Bristol Myers Squibb. AMH: advisory board member for Amgen, Bristol Myers Squibb, Merck Sharp and Dohme, Novartis, Pierre-Fabre, and Qbiotics, GVL: advisor: Aduro Biotech, Agenus, Amgen, Array Biopharma, Boehringer, Bristol Myers Squibb, Evaxion, Highlight Therapeutics S.L, Merck Sharp and Dohme, Novartis, Pierre Fabre, QBiotics, Regeneron, Specialised Therapeutics Australia. AM: advisory board: Bristol Myers Squibb, Merck Sharp and Dohme, Novartis, Roche, Pierre-Fabre, QBiotics. MC: consultant advisor: Amgen, Bristol Myers Squibb, Eisai, Ideaya, Merck Sharp and Dohme, Nektar, Novartis, Oncosec, Pierre-Fabre, Qbiotics, Regeneron, Roche; honoraria: Bristol Myers Squibb, Merck Sharp and Dohme, Novartis. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
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5. Efficacy and safety of anti-PD1 monotherapy or in combination with ipilimumab after BRAF/MEK inhibitors in patients with BRAF mutant metastatic melanoma.

Author

Pires da Silva I, Zakria D, Ahmed T, Trojanello C, Dimitriou F, Allayous C, Gerard C, Zimmer L, Lo S, Michielin O, Lebbe C, Mangana J, Ascierto PA, Johnson DB, Carlino M, Menzies A, and Long G

Subjects
Female, Humans, Ipilimumab therapeutic use, Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors, Mutation, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Proto-Oncogene Proteins B-raf genetics, Melanoma, Cutaneous Malignant, Brain Neoplasms drug therapy, Melanoma drug therapy, Melanoma genetics, Melanoma pathology, Neoplasms, Second Primary drug therapy, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors therapeutic use, Skin Neoplasms drug therapy, Skin Neoplasms genetics, Skin Neoplasms pathology
Abstract

Background: Patients with V600BRAF mutant metastatic melanoma have higher rates of progression-free survival (PFS) and overall survival (OS) with first-line anti-PD1 (PD1]+anti-CTLA-4 (IPI) versus PD1. Whether this is also true after BRAF/MEKi therapy is unknown. We aimed to determine the efficacy and safety of PD1 versus IPI +PD1 after BRAF/MEK inhibitors (BRAF/MEKi)., Methods: Patients with V600BRAF mutant metastatic melanoma treated with BRAF/MEKi who had subsequent PD1 versus IPI+PD1 at eight centers were included. The endpoints were objective response rate (ORR), PFS, OS and safety in each group., Results: Of 200 patients with V600E (75%) or non-V600E (25%) mutant metastatic melanoma treated with BRAF/MEKi (median time of treatment 7.6 months; treatment cessation due to progressive disease in 77%), 115 (57.5%) had subsequent PD1 and 85 (42.5%) had IPI+PD1. Differences in patient characteristics between PD1 and IPI+PD1 groups included, age (med. 63 vs 54 years), time between BRAF/MEKi and PD1±IPI (16 vs 4 days), Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≥1 (62% vs 44%), AJCC M1C/M1D stage (72% vs 94%) and progressing brain metastases at the start of PD1±IPI (34% vs 57%). Median follow-up from PD1±IPI start was 37.8 months (95% CI, 33.9 to 52.9). ORR was 36%; 34% with PD1 vs 39% with IPI+PD1 (p=0.5713). Median PFS was 3.4 months; 3.4 with PD1 vs 3.6 months with IPI+PD1 (p=0.6951). Median OS was 15.4 months; 14.4 for PD1 vs 20.5 months with IPI+PD1 (p=0.2603). The rate of grade 3 or 4 toxicities was higher with IPI+PD1 (31%) vs PD1 (7%). ORR, PFS and OS were numerically higher with IPI+PD1 vs PD1 across most subgroups except for females, those with <10 days between BRAF/MEKi and PD1±IPI, and those with stage III/M1A/M1B melanoma. The combination of ECOG PS=0 and absence of liver metastases identified patients with >3 years OS (area under the curve, AUC=0.74), while ECOG PS ≥1, progressing brain metastases and presence of bone metastases predicted primary progression (AUC=0.67)., Conclusions: IPI+PD1 and PD1 after BRAF/MEKi have similar outcomes despite worse baseline prognostic features in the IPI+PD1 group, however, IPI+PD1 is more toxic. A combination of clinical factors can identify long-term survivors, but less accurately those with primary resistance to immunotherapy after targeted therapy., Competing Interests: Competing interests: IPdS had travel support by BMS and MSD, and speaker fee by Roche, BMS and MSD. FD receives/received honoraria and travel support from Merck Sharp and Dohme and Sun Pharma. CA had travel support by by Roche, BMS and AMGEN. LZ has received honoraria from Roche, BMS, MSD, Novartis, Pierre Fabre; has served as consultant on advisory boards from BMS, Novartis, Pierre Fabre, Sunpharma, Sanofi, MSD; and has received research funding to institution from Novartis; Travel support: BMS, Pierre Fabre, Sanofi, Amgen, Novartis, Sunpharma. OM has received honoraria as speaker, consultancy or advisory role: BMS, Roche, Amgen, MSD, Novartis, GSK, Pierre-Fabre; and has received direct Research Funding: BMS, MSD and Amgen. CL has served on advisory boards for Bristol-Myers Squibb, MSD, Amgen, Novartis, Pierre Fabre, Roche, Sanofi, Merck. JM has intermittent project focused consultant or advisory relationships with Merck/Pfizer, Merck Sharp and Dohme, Amgen, Novartis, Sanofi, Bristol Myers Squibb and Pierre Fabre and has received travel support from Ultrasun, L’ oreal, Merck Sharp and Dohme, Bristol Myers and Squibb und Pierre Fabre outside of the submitted work. PAA has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp and Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health, ValoTX, Replimmune. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. Travel support from Pfizer. DBJ has served on advisory boards or as a consultant for BMS, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko, has received research funding from BMS and Incyte, and has patents pending for use of MHC-II as a biomarker for immune checkpoint inhibitor response, and abatacept as treatment for immune-related adverse events. MC is a consultant advisor for Bristol-Myers Squibb, Merck Sharpe & Dohme, Amgen, Novartis, Pierre Fabre, Roche, Sanofi, Merck and Co, Ideaya, Regeneron, Nektar, Eisai, Oncosec, Provectus and Q biotics AM has served on advisory boards for BMS, MSD, Novartis, Roche, Pierre-Fabre and QBiotics. GL is consultant advisor for Amgen Inc, Agenus, Array Biopharma, Boehringer Ingelheim, Bristol-Myers Squibb, Evaxion, Hexel AG, Highlight Therapeutics, Merck Sharpe and Dohme, Novartis Pharma, OncoSec, Pierre Fabre, QBiotics, Regeneron, Specialised Therapeutics Australia. DZ, TA, CT, CG, SL have no disclosures., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2022
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6. Impact of COVID-19 outbreak on cancer immunotherapy in Italy: a survey of young oncologists.

Author

Ottaviano M, Curvietto M, Rescigno P, Tortora M, Palmieri G, Giannarelli D, Aieta M, Assalone P, Attademo L, Avallone A, Bloise F, Bosso D, Borzillo V, Buono G, Calderoni G, Caputo F, Cartenì G, Cavallero D, Cavo A, Ciardiello F, Conca R, Conteduca V, De Falco S, De Felice M, De Laurentiis M, De Placido P, De Placido S, De Santo I, De Stefano A, Della Corte CM, Di Franco R, Di Lauro V, Fabbrocini A, Federico P, Festino L, Giordano P, Giuliano M, Gridelli C, Grimaldi AM, Lia M, Marretta AL, Massa V, Mennitto A, Merler S, Merz V, Messina C, Messina M, Milano M, Minisini AM, Montesarchio V, Morabito A, Morgillo F, Mucci B, Nappi L, Napolitano F, Paciolla I, Pagliuca M, Palmieri G, Parola S, Pepe S, Petrillo A, Piantedosi F, Piccin L, Picozzi F, Pietroluongo E, Pignata S, Prati V, Riccio V, Rosanova M, Rossi A, Russo A, Salati M, Santabarbara G, Sbrana A, Simeone E, Silvestri A, Spada M, Tarantino P, Taveggia P, Tomei F, Vincenzo T, Trapani D, Trojanello C, Vanella V, Vari S, Ventriglia J, Vitale MG, Vitiello F, Vivaldi C, von Arx C, Zacchi F, Zampiva I, Zivi A, Daniele B, and Ascierto PA

Subjects
Adult, Antineoplastic Agents, Immunological adverse effects, B7-H1 Antigen antagonists & inhibitors, B7-H1 Antigen immunology, Betacoronavirus pathogenicity, COVID-19, CTLA-4 Antigen antagonists & inhibitors, CTLA-4 Antigen immunology, Coronavirus Infections immunology, Coronavirus Infections prevention & control, Coronavirus Infections transmission, Drug Prescriptions statistics & numerical data, Female, Geography, Humans, Infection Control standards, Italy epidemiology, Male, Medical Oncology standards, Neoplasms immunology, Oncologists statistics & numerical data, Pandemics prevention & control, Pneumonia, Viral immunology, Pneumonia, Viral prevention & control, Pneumonia, Viral transmission, Practice Patterns, Physicians' standards, Practice Patterns, Physicians' statistics & numerical data, Prevalence, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor immunology, SARS-CoV-2, Surveys and Questionnaires statistics & numerical data, Time-to-Treatment, Antineoplastic Agents, Immunological administration & dosage, Betacoronavirus immunology, Coronavirus Infections epidemiology, Medical Oncology statistics & numerical data, Neoplasms drug therapy, Pneumonia, Viral epidemiology
Abstract

Background: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region., Methods: This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ 2 test for trends relative to the questions with 3 or more options., Results: This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones., Conclusion: Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2020
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