Three-years real-world evidence of adjuvant dabrafenib plus trametinib (DT) in patients with resected melanoma in Spain (GEM 1901 - DESCRIBE-AD)

Background: DT combination has shown efficacy in the adjuvant setting for BRAF-mutated melanoma (BMM) patients (pts) in clinical trials. Previous reports from DESCRIBE-AD resulted in promising overall survival (OS) rates at 12 months. Methods: An observational retrospective study was carried out in 25 GEM sites in Spain. Histologically confirmed and resected BMM pts previously treated with DT according to standard clinical practice in the adjuvant setting were included. Only surgical resection was allowed as a prior treatment to DT. DT discontinuation rate and time to treatment discontinuation were the primary objective. Secondary objectives included safety and efficacy of the combination. Here, we report 3-year results for OS. Results: From 10/2020 to 03/2021, 65 pts were included. Median age was 58 years, 55% were male and 60%, 25%, and 14% had an ECOG PS 0/1/Uk respectively, one patient presented ECOG 3. Allocation of stage IIIA, IIIB and IIIC according to TNM AJCC 7th edition was 29%, 26% and 32%, respectively. There were 3 pts diagnosed at stage I/II but considered of risk, and 2 pts with stage IV but completely resected, all considered for adjuvant DT. Ulceration was present in 40%, Breslow ≥2 mm in 71%, and nodes were microscopically and macroscopically affected in 39% and 22% of pts, respectively. Only 9.2% of pts discontinued DT prematurely due to toxicity and 21.2% had dose reductions to manage toxicity. After a median follow-up of 36.2 m (range: 13-51.1), the overall OS rate at 3-years was 83.5% (95% CI: 74.5-93.5). According to AJCC 7 stage at diagnosis, the 3-years OS rate was 95.2% (95% CI: 86.6-100), 75% (56-100), and 76.8% (60.7-97.2) for stage I-II-IIIA, IIIB, and IIIC-IV respectively. Throughout the study period 11 (16.9%) pts died, of which 10 died due to disease progression and one due to COVID-19 infection. Conclusions: Adjuvant treatment with DT for melanoma achieved good treatment compliance and has proven efficacy in the real world. Adjuvant DT has a clinical impact in survival in line with previous clinical trial COMBI-AD. Editorial acknowledgement: We acknowledge Mfar Clinical Research staff for their assistance in the development of this . Legal entity responsible for the study: Grupo Español Multidisciplinar en Melanoma (GEM). Funding: Grupo Español Multidisciplinar en Melanoma (GEM) as Sponsor with Industry partner NOVARTIS. Disclosure: P. Cerezuela-Fuentes: Financial Interests, Personal, Other, Consultancy, conference,congress attendance/infrastructure: BMS, MSD, Pierre Fabre, Roche, Sanofi, SunPharma. J. Martín-Liberal: Financial Interests, Personal, Other, Lecture fees: Astellas, MSD;Financial Interests, Personal, Other, Lecture fees, advisory fees: Bristol Myers Squibb, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi;Non-Financial Interests, Personal, Member, membership or affiliation: ASCO, ESMO, SEOM, GEM, EORTC, SOGUG, GEIS. L.A. Fernández-Morales: Financial Interests, Personal, Invited Speaker, Speak at sponsored meetings: BMS, MSD, Pierre-Fabre, Roche;Financial Interests, Personal, Other, Speak at sponsored meetings and advisory role: Novartis. J. Medina Martinez: Financial Interests, Personal, Other, Speaker, consultancy or advisory role or similar activity: Novartis, Roche, Pierre Fabre, BMS, MSD, Sanofi. M. Quindós: Financial Interests, Personal, Other, speaker, consultancy and advisory: AstraZeneca, GSK, Merck Sharp & Dohme, Novartis, PharmaMar, Roche, Bristol Myers Squibb, Pierre Fabre;Financial Interests, Institutional, Other, Clinical trials: Merck Sharp & Dohme, Roche, Bristol Myers Squibb. A. García Castaño: Non-Financial Interests, Advisory Role: Bristol, MSD, Novartis. T. Puértolas: Financial Interests, Personal, Invited Speaker, Speaker and advisory role: BMS, Novartis;Financial Interests, Personal, Invited Speaker: Roche, MSD, Sun-Pharma;Financial Interests, Personal, Other, Speaker and advisory role: Pierre-Fabre;Financial Interests, Personal, Advisory Role: Sanofi;Financial Interests, Institutional, Other, Clinical trial: Roche, BMS, Apexi en Inc, Aduro Biotech, Alkermes Inc;Non-Financial Interests, Institutional, Other, congresses inscriptions: Lilly, Sun-Pharma, Novartis, Roche, MSD;Non-Financial Interests, Institutional, Leadership Role, Vocal: GEM (Grupo Español Multidisciplinar de Melanoma);Non-Financial Interests, Institutional, Affiliate: SEOM (Sociedad Española de Oncología Médica), GEM (Grupo Español Multidisciplinar de Melanoma). P. Ayala de Miguel: Financial Interests, Personal, Invited Speaker, Public speaking: Novartis, Merck Sharp & Dohme, Sanofi, Pierre-Fabré. B. Campos: Financial Interests, Personal, Other, Speaker or advisory role: Roche, BMS, Sanofi, Novartis, Pierre-Fabre, Sun Pharma;Financial Interests, Personal, Other, Speaker role: AstraZeneca, Merck, ROVI, Leo Pharma. E. Espinosa: Financial Interests, Personal, Advisory Role, Advisory: BMS, MSD;Financial Interests, Personal, Other, Advisory, educational activities: Novartis;Financial Interests, Personal, Invited Speaker, Advisory, educational activities: Pierre Fabre;Financial Interests, Personal, Funding, Funding for translational investigation: Roche;Non-Financial Interests, Personal, Member, Vicepresident: Grupo Español Multidisciplinario de Melanoma. A. Rodríguez-Lescure: Financial Interests, Personal, Advisory Role: Pfizer, Novartis, ROCHE, AstraZeneca, Daiichi Sankyo, Seagen;Financial Interests, Personal, Invited Speaker, Public speaking: Pierre-Fabre;Financial Interests, Institutional, Research Grant, Grant for Clinical Trials: BMS, Lilly, Roche, Novartis, Amgen, Pzifer, Zimeworks, AstraZeneca, G1 Therapeutics, Bayer. L. Espasa Font: Financial Interests, Personal, Full or part-time Employment: Novartis. G. Belaustegui Ferrández: Financial Interests, Personal, Full or part-time Employment: Novartis. All other authors have declared no conflicts of interest.

1061P Safety of cemiplimab for advanced cutaneous squamous cell carcinoma: The Spanish named patient programme

Background: Cemiplimab is a programmed cell death receptor-1 inhibitor with antitumour activity for cutaneous squamous cell carcinoma (CSCC) and acceptable safety proved in its pivotal trial. We provide the first data on cemiplimab safety in daily practice from the named patient programme (NPP) for advanced CSCC in Spain. Methods: This cemiplimab NPP was performed from March 2019 to March 2020. It included patients aged ≥18 years with advanced CSCC and ineligible for surgery, radiation therapy or clinical trials. The cemiplimab safety was assessed according to treatment-emergent adverse events (TEAEs) reported until March 2021. Results: 140 patients were included (median age [interquartile range, IQR] 77.0 [65.0-84.0] years;age ≥80 38%;men 71.7%;≥1 comorbidity 83%;ECOG 0-1 86.3%;locally advanced CSCC 60.7%;cemiplimab as first-line therapy 67.7%). Cemiplimab was received for a median (IQR) of 8.0 (3.0-14.0) cycles. Fifty-eight (41.4%) patients showed ≥1 of the 163 TEAEs reported, which most frequently included diarrhoea n=7, asthenia n=6, constipation n=4 and abdominal pain n=4. Fourteen (8.6%) were immune-mediated, mainly bronchitis n=2, pneumonitis n=2 and hepatitis n=2. Seventy-eight (47.9%) TEAEs were grade ≥3, most frequently pneumonia n=3, COVID-19 n=3, general physical health deterioration n=2, pyrexia n=2, renal transplant failure n=2, sepsis n=2, acute kidney injury n=2 and respiratory failure n=2. Twenty-one (12.9%) were treatment-related (TREAEs): 11 (6.7%) were grade 1-2 (diarrhoea n=3 and asthenia, hepatotoxicity, malnutrition, odynophagia, polymyalgia rheumatica, pneumonitis, pruritus, and skin toxicity), 9 (5.5%) grade 3 (acute kidney injury, adrenal insufficiency, abdominal pain, blood creatinine increased, dysphagia, haematuria, immune-mediated enterocolitis, panniculitis, surgical wound infection) and 1 (0.6%) unknown grade. Cemiplimab was withdrawn due to TREAEs in only 5 (3.6%) patients. The TEAE outcome was fatal in 29 (17.8%);none related to cemiplimab. Conclusions: This NPP supports the real-life safety of cemiplimab for CSCC, showing an acceptable safety profile consistent with previous reports. Editorial acknowledgement: Editorial assistance was provided by Esther Álvarez-García at Dynamic Science S.L., funded by Sanofi. Legal entity responsible for the study: Sanofi. Funding: Sanofi. Disclosure: E. Muñoz Couselo: Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Pierre Fabre;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Other, Honoraria: Amgen;Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb;Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme;Financial Interests, Personal, Other, Honoraria: Novartis;Financial Interests, Personal, Other, Honoraria: Pierre Fabre;Financial Interests, Personal, Other, Honoraria: Roche;Financial Interests, Personal, Principal Investigator: Amgen;Financial Interests, Personal, Principal Investigator: Bristol-Myers Squibb;Financial Interests, Personal, Principal Investigator: GlaxoSmithKline;Financial Interests, Personal, Principal Investigator: Merck Sharp & Dohme;Financial Interests, Personal, Principal Investigator: Novartis;Financial Interests, Personal, Principal Investigator: Pierre Fabre;Financial Interests, Personal, Principal Investigator: Roche;Financial Interests, Personal, Principal Investigator: Sanofi. A. Soria: Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Invited Speaker: Sanofi Aventis;Financial Interests, Personal, Invited Speaker: Roche Pharma;Financial Interests, Personal, Invited Speaker: Merck Serono;Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme;Financial Interests, Perso al, Invited Speaker: Bristol-Myers Squibb;Financial Interests, Personal, Invited Speaker: Pierre Fabre;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Sanofi Aventis;Financial Interests, Personal, Advisory Board: Roche Pharma;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Board: Pierre Fabre;Financial Interests, Personal, Principal Investigator: Novartis;Financial Interests, Personal, Principal Investigator: Sanofi Aventis;Financial Interests, Personal, Principal Investigator: Roche Pharma;Financial Interests, Personal, Principal Investigator: Merck Serono;Financial Interests, Personal, Principal Investigator: Merck Sharp & Dohme;Financial Interests, Personal, Principal Investigator: Bristol-Myers Squibb;Financial Interests, Personal, Principal Investigator: Pierre Fabre. O. Sanmartin: Financial Interests, Personal, Invited Speaker: Sanofi Genzyme;Financial Interests, Personal, Advisory Board: Sanofi Genzyme;Financial Interests, Personal, Officer: Sanofi Genzyme;Financial Interests, Personal, Principal Investigator: Sanofi Genzyme;Financial Interests, Personal, Invited Speaker: Roche Pharma;Financial Interests, Personal, Advisory Board: Roche Pharma;Financial Interests, Personal, Officer: Roche Pharma;Financial Interests, Personal, Principal Investigator: Roche Pharma. J. Cañueto: Financial Interests, Personal, Invited Speaker: Hoffman-La Roche;Financial Interests, Personal, Invited Speaker: Sanofi-Genzyme;Financial Interests, Personal, Invited Speaker: AbbVie;Financial Interests, Personal, Invited Speaker: LeoPharma;Financial Interests, Personal, Other, Consultancy: Sanofi-Genzyme;Financial Interests, Personal, Other, Consultancy: InflaRx;Financial Interests, Personal, Other, Consultancy: Almirall. S. Beá Ardébol: Financial Interests, Personal, Invited Speaker: Meda;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: SunPharma;Financial Interests, Personal, Other, Trial subinvestigator: Sanofi Aventis;Financial Interests, Personal, Other, Trial subinvestigator: SunPharma;Financial Interests, Personal, Other, Trial subinvestigator: PellePharma. R. Fernández-de-Misa Cabrera: Financial Interests, Personal, Advisory Board: Sanofi. A.J. Cunquero-Tomás: Financial Interests, Personal, Invited Speaker: BMS;Financial Interests, Personal, Invited Speaker: Pierre-Fabre;Financial Interests, Personal, Writing Engagements: Sanofi;Financial Interests, Personal, Other, 2021 EADO/WMC Congress inscription fee: Sanofi. L. Fernández Franco: Non-Financial Interests, Personal, Invited Speaker: Merck;Non-Financial Interests, Personal, Invited Speaker: Sanofi;Non-Financial Interests, Personal, Invited Speaker: Servier. I. Romero: Financial Interests, Personal, Invited Speaker: Pharmamar;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: GSK;Financial Interests, Personal, Invited Speaker: Clovis;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Advisory Board: Pharmamar;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: GSK;Financial Interests, Personal, Advisory Board: Clovis;Financial Interests, Personal, Advisory Board: AstraZeneca. J. Medina Martínez: Non-Financial Interests, Personal, Invited Speaker: Roche;Non-Financial Interests, Personal, Speaker’s Bureau: Roche;Non-Financial Interests, Personal, Advisory Board: Roche;Non-Financial Interests, Personal, Invited Speaker: Novartis;Non-Financial Interests, Personal, Speaker’s Bureau: Novartis;Non-Financial Interests, Personal, Advisory Board: Novartis;Non-Financial Interests, Personal, Invited Speaker: BMS;Non-Financial Interests, Personal, Speaker’s Bureau: BMS;Non-Financial Interests, Personal, Ad isory Board: BMS;Non-Financial Interests, Personal, Invited Speaker: MSD;Non-Financial Interests, Personal, Speaker’s Bureau: MSD;Non-Financial Interests, Personal, Invited Speaker: Pierre Fabre;Non-Financial Interests, Personal, Speaker’s Bureau: Pierre Fabre;Non-Financial Interests, Personal, Advisory Board: Pierre Fabre;Non-Financial Interests, Personal, Invited Speaker: Merk;Non-Financial Interests, Personal, Speaker’s Bureau: Merk;Non-Financial Interests, Personal, Invited Speaker: Sanofi;Non-Financial Interests, Personal, Speaker’s Bureau: Sanofi;Non-Financial Interests, Personal, Advisory Board: Sanofi;Non-Financial Interests, Personal, Invited Speaker: Servier. All other authors have declared no conflicts of interest.