Abstract 1016P
Background
For patients (pts) with stage IIIB/IV NSCLC without oncogenic addiction (OA), immuno-checkpoint inhibitors (ICI) have emerged as a standard first-line treatment. Literature suggests a lower efficacy of ICI as single treatment in pts with OA, notably EGFR mutation or ALK/ROS1 rearrangement. Assuming adding chemotherapy to immunotherapy (CT-IO) may improve the management of pts with OA, we implemented a trial to assess the efficacy of this combination in this setting.
Methods
We conducted a national, open, multicentre, non-randomized Phase II Study with two parallel cohorts: A (Platinum-Pemetrexed-Atezolizumab-Bevacizumab) and B (Platinum-Pemetrexed-Atezolizumab). Main eligibility criteria were: stage IIIB/IV NSCLC with EGFR mutation or ALK/ROS1 rearrangement progression after ≥1 targeted therapy and no prior chemotherapy and eligible for Bevacizumab (A). The primary endpoint was objective response rate (ORR) after 4 cycles (RECIST 1.1) evaluated by masked, independent central review. The secondary endpoints were PFS, OS and safety profile. For cohort A, an ORR of 35% (p0) was undesirable (and p1=50% expected). For cohort B, p0=30% and p1=45%.
Results
149 pts were included (71 in A, 78 in B): for A/B respectively, mean age, 60.4/66.1 years; men 31/49%; alteration for EGFR 87/90%, ALK 13/5%, ROS1 0/6%. ORR was 58.2% (90% CI 47.4-68.4%, p<0.01) in A and 46.5% (90% CI 36.3-56.8%, p<0.01) in B. Disease control rate at 12 weeks was 89.6% (A) and 81.7% (B). Median PFS and OS were respectively 7.3 months (95% CI 6.9- 9.0), 17.2 months (95% CI 13.7-NA) in A and 7.2 months (95% CI 5.7-9.2), 16.8 months (95% CI 13.5-NA) in B. Grade 3-4 adverse events (AE) occurred in 69.1/51.4% (A/B). Severe immune-related AE occurred in 27.9/15.3% (A/B). No toxicity-related death was observed.
Conclusions
Combination approach of Platinum-Pemetrexed-Atezolizumab-Bevacizumab or Platinum-Pemetrexed-Atezolizumab achieved promising efficacy in metastatic EGFR/ALK mutated NSCLC after TKI failure, with acceptable tolerance profile.
Clinical trial identification
NCT04042558.
Editorial acknowledgement
Legal entity responsible for the study
Groupe Francais de Pneumo-Cancerologie (GFPC).
Funding
This trial is granted by financial support and drug supply (Atezolizumab, Bevacizumab) from Roche S.A.S that is not involved in the design and conduct of the study, nor in the collection, management, analysis and interpretation of the data.
Disclosure
O. Bylicki: Financial Interests, Personal, Expert Testimony: BMS, MSD, AstraZeneca; Non-Financial Interests, Personal and Institutional, Principal Investigator: MSD, AstraZeneca. C. Ricordel: Financial Interests, Personal, Advisory Board: BMS, Takeda, AstraZeneca; Financial Interests, Personal, Funding: AstraZeneca. L. Bigay-Game: Financial Interests, Personal, Advisory Board: BMS, MSD, Takeda, AstraZeneca, Viatris, Ipsen, Amgen, Pfizer. M. Geier: Financial Interests, Institutional, Research Grant: BMS, ROCHE; Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, Pfizer, Sanofi, BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca. C. Decroisette: Financial Interests, Personal, Advisory Board: Sanofi, Janssen Cilag, AstraZeneca, Takeda, BMS, Sandoz, Novartis, Roche, Lilly, Pfizer. C. Daniel: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Novartis. F. Guisier: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, MSD, Roche, Amgen, Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Takeda, Pfizer. A. Swalduz: Financial Interests, Personal, Advisory Board: Lilly, Roche; Financial Interests, Personal, Invited Speaker: MSD. A.C. Toffart: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Amgen, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Leo Pharma, MSD, Nutrician, Novartis, Pfizer. H. Doubre: Financial Interests, Personal, Advisory Board: BMS, Amgen; Financial Interests, Personal, Invited Speaker: Leo Pharma; Financial Interests, Personal, Research Grant: MSD, Pfizer; Financial Interests, Personal, Other, Travel Congress: Novartis, Roche. J.M. Peloni: Financial Interests, Personal, Advisory Board: AstraZeneca. H. Morel: Financial Interests, Personal, Invited Speaker: Takeda. R. Veillon: Financial Interests, Personal, Invited Speaker: Amgen, BMS, Roche; Financial Interests, Personal, Advisory Board: Janssen Cilag, Takeda; Financial Interests, Personal, Expert Testimony: AstraZeneca; Non-Financial Interests, Personal, Other, congress registration: Pfizer, Roche; Financial Interests, Institutional, Research Grant: Merck, Takeda, Novartis, GSK, AstraZeneca. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, AbbVie, BMS, MSD, Novartis, Sanofi, Takeda, Pfizer, PharmaMar. C. Chouaid: Financial Interests, Personal, Advisory Board: Astra Zeneca, Boehringer, Sanofi, Roche, MSD, Lilly, Novartis, Takeda, Bayer, Pfizer, Amgen. All other authors have declared no conflicts of interest.