Abstract 1273P
Background
PDL-1 inhibitors such as D have shown efficacy in the management of advanced NSCLC. We investigated the effect of D as a maintenance strategy after chemotherapy in the SAFIR02-LUNG Immuno substudy.
Methods
ALK-/EGFRwt NSCLC pts after a CR/PR/SD to 4 cycles of platinum-based chemotherapy were eligible. Pts were enrolled in 2 substudies, based on NGS + CGH performed centrally on a mandatory tissue or liquid biopsy. The bio-guided substudy, for NSCLC with somatic alterations (including KRAS, STK11, BRAF mutations), will be reported separately. In the immuno substudy, pan-negative NSCLC pts were randomized 2:1 either on D or SoC. The primary endpoint was Progression-Free Survival (PFS). A prespecified subgroup analysis was performed according to positive (>=1%) or negative (<1%) PDL-1 immunohistochemistry (IHC) expression.
Results
Among the 183 randomized pts (121 were on D), median age was 62, 37.7% were female, 12.6% never-smoker, 92.9% had a non-squamous. 162 pts had progressed or died. With a median follow-up of 23.8 months (mo), median PFS was 3.0 mo (95% confidence interval [CI], 2.3 to 4.4) with D versus 3.0 mo (95%CI=2.0-5.1) with SoC (HR for disease progression or death 0.87; 95%CI=0.63 to 1.22; p=0.426). Median OS was 17.0 mo (95%CI=12.1-19.5) with D versus 14.9 mo (95% CI=10.5-22.0) with SoC (HR for death 0.91; 95%CI=0.61-1.37; p=0.661). PDL-1 IHC was performed on 60 samples (42 on D and 18 on SoC). The HR for PFS was 0.29 (95%CI=0.11-0.75; p=0.011) in PDL-1+ pts treated by D compared to SoC vs 0.71 (95%CI=0.31-1.60; p=0.408) in PLD-1- pts (interaction p=0.036). The HR for OS was 0.32 (95%CI=0.12-0.83; p=0.020), vs 1.20 (95%CI=0.48-2.99; p=0.701) in PDL-1+ and PDL-1 pts respectively (interaction p=0.039). Grade 3 or 4 treatment-related adverse events occurred in 15 pts out of 121 pts on D (17.1%).
Conclusions
In this substudy, pts were negatively selected based on a central molecular analysis. In this population, maintenance D, vs SoC, did suggest a positive effect on PFS and OS in the PDL-1 positive subgroup but not in the overall population. This finding requires validation in larger studies. There was no new finding in D toxicity profile.
Clinical trial identification
NCT02117167; EudraCT 2013-001653-27.
Editorial acknowledgement
Legal entity responsible for the study
Unicancer.
Funding
Fondation Arc and AstraZeneca.
Disclosure
F. Barlesi: Honoraria (self), Honoraria (institution), Research grant/Funding (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Honoraria (institution), Research grant/Funding (institution): Bayer; Honoraria (self), Honoraria (institution), Research grant/Funding (institution), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Boehringer–Ingelheim; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly Oncology; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: F. Hoffmann–La Roche Ltd; Honoraria (self), Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Merck; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Pierre Fabre; Honoraria (self), Honoraria (institution), Research grant/Funding (institution): Pfizer ; Honoraria (self), Honoraria (institution), Research grant/Funding (institution): Takeda; Honoraria (institution), Research grant/Funding (institution): AbbVie; Honoraria (institution), Research grant/Funding (institution): ACEA; Honoraria (institution), Research grant/Funding (institution): Amgen; Honoraria (institution), Research grant/Funding (institution): Eisai; Honoraria (institution), Research grant/Funding (institution): Genentech; Honoraria (institution), Research grant/Funding (institution): Ipsen; Honoraria (institution), Research grant/Funding (institution): Ignyta; Honoraria (institution), Research grant/Funding (institution): Innate Pharma; Honoraria (institution), Research grant/Funding (institution): Loxo; Honoraria (institution), Research grant/Funding (institution): MedImmune; Honoraria (institution), Research grant/Funding (institution): Sanofi-Aventis .P. Tomasini: Research grant/Funding (institution), Non-remunerated activity/ies: Roche; Research grant/Funding (institution), Non-remunerated activity/ies: AZ; Research grant/Funding (institution), Non-remunerated activity/ies: BI; Research grant/Funding (institution), Non-remunerated activity/ies: BMS; Research grant/Funding (institution), Non-remunerated activity/ies: MSD; Research grant/Funding (institution), Non-remunerated activity/ies: Takeda; Research grant/Funding (institution), Non-remunerated activity/ies: Novartis. J. Raimbourg: Advisory/Consultancy: novartis; Advisory/Consultancy: AZ; Advisory/Consultancy: BMS ; Advisory/Consultancy: Takeda ; Advisory/Consultancy, Non-remunerated activity/ies: Bayer; Non-remunerated activity/ies: Roche. A-E. Quoix: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Speaker Bureau/Expert testimony: Chugaï; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Takeda; Non-remunerated activity/ies, (interview during ASCO 2019): Medscape. A-C. Madroszyk Flandin: Advisory/Consultancy, Speaker Bureau/Expert testimony: ASTRA-ZENECA ; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Travel/Accommodation/Expenses: PFIZER ; Travel/Accommodation/Expenses: MSD. J. Mazieres: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Pierre Fabre ; Advisory/Consultancy: DAIICHI; Advisory/Consultancy: Novartis; Advisory/Consultancy: Hengrui; Advisory/Consultancy: BLUEPRINT; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Takeda. O. Molinier: Advisory/Consultancy: Takeda; Advisory/Consultancy: BMS; Advisory/Consultancy: Astra-zeneca; Advisory/Consultancy: MSD. C. Audigier-Valette: Advisory/Consultancy, Travel/Accommodation/Expenses, Non-remunerated activity/ies: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses, Non-remunerated activity/ies: Boehringer Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses, Non-remunerated activity/ies: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses, Non-remunerated activity/ies: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses, Non-remunerated activity/ies: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: AbbVie; Advisory/Consultancy: FoundationOne; Advisory/Consultancy: Takeda .D. Moro-Sibilot: Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): Takeda; Honoraria (self): Lilly; Honoraria (institution): AbbVie; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche; Honoraria (self): Novartis. H. Morel: Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Leo Pharma; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Vifor; Travel/Accommodation/Expenses: Fresenius; Travel/Accommodation/Expenses: Nutricia; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Boehringer; Travel/Accommodation/Expenses: Takeda; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Roche. P-J. Souquet: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: AZ. J. Adam: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche. J-C. Soria: Honoraria (self), Advisory/Consultancy: Astex; Honoraria (self), Advisory/Consultancy: Tarveda; Honoraria (self), Advisory/Consultancy: Symphogen; Honoraria (self), Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Mission Therapeutics; Honoraria (self), Advisory/Consultancy: Merus; Honoraria (self), Advisory/Consultancy: Gammamabs; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Clovis; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Blend Therapeutics; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy, Full/Part-time employment, ASTRAZENECA - Was a full time employee from Sept 2017 to Dec 2019: AstraZeneca; Shareholder/Stockholder/Stock options: Gritstone. B. Besse: Honoraria (institution), Research grant/Funding (institution): AbbVie; Honoraria (institution), Research grant/Funding (institution): Tolero Pharmaceuticals; Honoraria (institution), Research grant/Funding (institution): Tiziana Pharma; Honoraria (institution), Research grant/Funding (institution): Takeda; Honoraria (institution), Research grant/Funding (institution): Spectrum Pharmaceuticals; Honoraria (institution), Research grant/Funding (institution): Servier; Honoraria (institution), Research grant/Funding (institution): Sanofi; Honoraria (institution), Research grant/Funding (institution): Roche-Genentech; Honoraria (institution), Research grant/Funding (institution): PharmaMar; Honoraria (institution), Research grant/Funding (institution): Pfizer; Honoraria (institution), Research grant/Funding (institution): OSE immunotherapeutics; Honoraria (institution), Research grant/Funding (institution): Onxeo; Honoraria (institution), Research grant/Funding (institution): Nektar; Honoraria (institution), Research grant/Funding (institution): MSD; Honoraria (institution), Research grant/Funding (institution): Merck KGaA; Honoraria (institution), Research grant/Funding (institution): Janssen; Honoraria (institution), Research grant/Funding (institution): Inivata; Honoraria (institution), Research grant/Funding (institution): Ipsen; Honoraria (institution), Research grant/Funding (institution): Ignyta; Honoraria (institution), Research grant/Funding (institution): GSK; Honoraria (institution), Research grant/Funding (institution): Eli Lilly; Honoraria (institution), Research grant/Funding (institution): Daiichi Sankyo; Honoraria (institution), Research grant/Funding (institution): Cristal Therapeutics; Honoraria (institution), Research grant/Funding (institution): Celgene; Honoraria (institution), Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (institution), Research grant/Funding (institution): BMS; Honoraria (institution), Research grant/Funding (institution): Blueprint Medicines; Honoraria (institution), Research grant/Funding (institution): BeiGene; Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): Amgen. All other authors have declared no conflicts of interest.