Durvalumab consolidation in patients with unresectable stage III non-small cell lung cancer with driver genomic alterations.

Autor: Riudavets M; Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France., Auclin E; Medical Oncology Department, Hôpital Européen Georges Pompidou, AP-HP Centre, Université de Paris, Paris, France., Mosteiro M; Medical Oncology Department, Institut Català d'Oncologia - ICO Hospitalet, Barcelona, Spain., Dempsey N; Medical Oncology Department, Jackson Memorial Hospital, Miami, FL, USA., Majem M; Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain., Lobefaro R; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milan, Milano, Italy., López-Castro R; Medical Oncology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain., Bosch-Barrera J; Medical Oncology Department, Catalan Institute of Oncology, Hospital Universitari Josep Trueta, Girona, Spain., Pilotto S; Medical Oncology Department, University and Hospital Trust of Verona, Verona, Italy., Escalera E; Medical Oncology Department, Hospital Clínico de Salamanca, Salamanca, Spain., Tagliamento M; Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France; Internal Medicine and Medical Specialties Departement, University of Genova, Genova, Italy., Mosquera J; Medical Oncology Department, Hospital Universitario A Coruña, A Coruña, Spain., Zalcman G; Medical Oncology Department, Hôpital Bichat-Claude Bernard, Paris, France., Aboubakar-Nana F; Division of Pneumology, Cliniques universitaires Saint-Luc, Bruxelles, Belgium., Ponce S; Medical Oncology Department, Hospital 12 de Octubre, Madrid, Spain., Dal Maso A; Medical Oncology Department, Istituto Oncologico Veneto IRCCS, Padova, Italy., Spotti M; Medical Oncology Department, Hospital Aleman, Buenos Aires, Argentina., Mielgo-Rubio X; Medical Oncology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain., Mussat E; Medical Oncology Department, Hôpital Européen Georges Pompidou, AP-HP Centre, Université de Paris, Paris, France., Reyes R; Medical Oncology Department, Hospital Clínic i Provincial de Barcelona, IDIBAPS, Barcelona, Spain., Benítez JC; Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France; Medical Oncology Department, Hospital Universitari Mutua Terrassa, Terrassa, Barcelona, Spain., Lupinacci L; Medical Oncology Department, Hospital Italiano, Buenos Aires, Argentina., Duchemann B; Medical Oncology Department, Hôpital Avicenne, Bobigny, France., De Giglio A; Medical Oncology Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Blaquier J; Medical Oncology Department, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina., Audigier-Valette C; Medical Oncology Department, Centre Hospitalier Toulon Sainte-Mousse, Toulon, France., Scheffler M; Internal Medicine I Department, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany., Nadal E; Medical Oncology Department, Institut Català d'Oncologia - ICO Hospitalet, Barcelona, Spain., Lopes G; Medical Oncology Department, Jackson Memorial Hospital, Miami, FL, USA., Signorelli D; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milan, Milano, Italy., Garcia-Campelo R; Medical Oncology Department, Hospital Universitario A Coruña, A Coruña, Spain., Menis J; Medical Oncology Department, University and Hospital Trust of Verona, Verona, Italy; Medical Oncology Department, Istituto Oncologico Veneto IRCCS, Padova, Italy., Bluthgen V; Medical Oncology Department, Hospital Aleman, Buenos Aires, Argentina., Campayo M; Medical Oncology Department, Hospital Universitari Mutua Terrassa, Terrassa, Barcelona, Spain., Recondo G; Medical Oncology Department, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina., Besse B; Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France., Planchard D; Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: David.PLANCHARD@gustaveroussy.fr., Mezquita L; Medical Oncology Department, Hospital Clínic i Provincial de Barcelona, IDIBAPS, Barcelona, Spain; Medical Oncology Department, Laboratory of Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2022 May; Vol. 167, pp. 142-148. Date of Electronic Publication: 2022 Mar 17.
DOI: 10.1016/j.ejca.2022.02.014
Abstrakt: Introduction: 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.
Material and Methods: 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.
Results: Out of 323 patients included, 43 patients had one dGA: KRASm (n = 26; 8 G12C), EGFRm (n = 8; 6 del19/ex21), BRAFm (n = 5; 4 V600E) and ALKr (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 KRASm G12C vs. 8.1 mo (5.8-NR) in the EGFRm del19/ex21 vs. 7.8 mo (7.7-NR) in the BRAFm V600E/ALKr (P = 0.02).
Conclusions: We observed limited activity of durvalumab consolidation in patients with stage III unresectable NSCLC with EGFR/BRAFm and ALKr but not for those harbouring KRASm. Larger prospective studies are needed to confirm these findings.
Competing Interests: Conflict of interest statement MMj: advisory and consultancy honoraria from Roche, Merck, BristolMyers Squibb, AstraZeneca, Amgen, Boehringer, Sanofi and Takeda; speaker honoraria from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Bayer, Amgen, Pfizer and Boehringer; grants from AstraZeneca and BristolMyers Squib, and travel/accommodation expenses from Roche, Merck and Lilly. RLC: honoraria from Kyowa Kirin, Pierre-Fabre, Takeda, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Roche, Merck Serono, Pfizer; consulting or advisory role from Roche, Astra-Zeneca, Boehringer Ingelheim, Aristo, Novartis; research funding from Roche, Bristol-Myers Squibb, MSD, Boehringer Ingelheim, AstraZeneca. JBB: grants and personal fees from Roche-Genentech, Pfizer, MSD, BMS, Astrazeneca, Novartis, Boehringer-Ingelheim, Vifor, Sanofi, LEO Pharma, outside the submitted work. SP: Consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Roche, Amgen. MT: travel grants from Roche, Bristol-Myers Squibb, AstraZeneca, Takeda; honoraria as medical writer from Novartis, Amgen. GZ: research grants from Roche-France, Bristol-Myers Squibb, and Takeda outside of the submitted work; perceived fees from Bristol-Myers Squibb, AstraZeneca, Pfizer, and Boehringer Ingelheim outside the submitted work; and reimbursement for international meetings assistance from AbbVie, Merck Sharp & Dohme, AstraZeneca, Bristol-Myers Squibb, and Roche-France. XM-R: Research grant funding from Brystol-Myers Squibb; consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim; honoraria (self) from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Roche, MSD; clinical trials research from Boehringer Ingelheim, Pfizer, Roche, Abbvie; travel, accommodations and expenses from Roche, Pfizer, Brysto-Myers Squibb. JB: educational grants by AMGEN. MSch: speaker and advisory role honoraria, travel accommodations from AMGEN, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis, Pfizer, Roche, Takeda; personal research support from AMGEN, Dracen Pharmaceuticals, Siemens Healthineers; institutional research support from Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche. EN: research support from Roche, Merck Serono, Bristol Myers Squibb and Pfizer and participated in advisory boards or lectures from Bristol Myers Squibb, Merck Serono, Merck Sharpe & Dohme, Lilly, Roche, Pfizer, Takeda, Bayer, Boehringer Ingelheim, Amgen and AstraZeneca. DS: Consulting, advisory role, honoraria from AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, Boehringer Ingelheim, Sanofi, Eli Lilly; travel grants from Roche. RGC: Consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda, Janseen, MSD, Roche, Pfizer, Eli Lilly, Amgen, Sanofi; honoraria (self) from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Roche, MSD, Takeda, Eli Lilly, Novartis; clinical trials research from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis. JMe: Advisory Boards/Honoraria/Speakers’ fee/Consultant for Astra-Zeneca, Boeringher Ingelheim, BMS, Roche, MSD; travel grants from Astra-Zeneca, Boeringher Ingelheim, BMS, Ipsen, Roche, MSD. VB: Clinical trial research from AstraZeneca, Roche, MSD; advisory role/consulting/speaker from Pfizer, MSD, AstraZeneca, Roche, Bristol, Merck, Takeda. MC: Advisory or Consultancy role from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, EUSA Pharma, Lilly, Roche; honoraria, lectures from Abbot, Bristol-Myers Squibb, EUSA Pharma, Ipsen, Novartis, Pfizer, Pierre Fabre, Roche; travel, expenses from Ipsen, Lilly, Merck, Pfizer, Pierre Fabre; institutional financial interests from Astra Zeneca, Merck, Roche, Pfizer. GR: consulting, advisory role or lectures from AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Merck Sharp & Dome, Pfizer, Roche, Takeda; sponsored Research Amgen and Janssen. BB: sponsored research at Gustave Roussy Cancer Centre Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. DP: consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; clinical trials research from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; travel, accommodations, expenses from AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer. LM: research grant/Funding (self) from Bristol Myers Squibb, Boehringer Ingelheim, Amgen, Stilla, Inivata; advisory/consultancy from Roche, Takeda; honoraria (self) from Bristol Myers Squibb, Roche, Takeda, AstraZeneca; travel/Accommodation/Expenses from Roche, Bristol Myers Squibb, Takeda, AstraZeneca; non-remunerated activity/ies from AstraZeneca. MR, EA, MMo, ND, EE, RL, JMo, FA, SP, AD, MSp, EM, RR, JCB, LL, BD, AdG, CAV and GL declare no conflicts of interest.
(Copyright © 2022. Published by Elsevier Ltd.)
Databáze: MEDLINE
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