Abstract 1079P
Background
Standard treatments for Stage IV non-small cell lung cancer (NSCLC) without common driver alterations include the use of immune checkpoint inhibitors (IO) as single agents or in combination with platinum chemotherapy (CT-IO), according to PD-L1 expression. However, IO activity in patients (pts) with novel oncogenic drivers’ alterations is not well explored.
Methods
We analyzed data of pts with advanced NSCLC treated with IO or CT-IO in any line between January 2016 to January 2022. Clinical and pathological data were extracted from our Institutional database. Pts harboring novel drive alterations (m-cohort) such as MET exon 14 skipping mutations, BRAF mutations (V600E or non-V600E), RET rearrangements, HER2 point mutations/exon 20 insertions or uncommon EGFR mutations/EGFR exon 20 insertions, and wild type pts (wt-cohort) were considered eligible for the analyses. Median progression free survival (mPFS) was estimated through Kaplan-Meier method and compared by log-rank test.
Results
We identified 64 pts for the m-cohort and 451 pts for the wt-cohort. With a median follow up of 33.8 months (m), mPFS was 4.73 m (0.95CI 3.93-5.85) overall and no statistical difference was observed between m-cohort and wt-cohort (mPFS 5.53 m (95%CI 4.73-6.97) vs 4.50 (95%CI 3.80-5.83), p 0.998). Moreover, mPFS was comparable across the different novel driver alteration’s subgroups. Considering only first line treatments, in m-cohort and wt-cohort respectively, 23 (56%) and 136 (62%) pts received IO while 18 (44%) and 85 (38%) were treated with CT-IO. Statistically significant differences were observed only for IO treatment in the PD-L1>50% group (mPFS 4.33 m (95%CI 1.97-NA) for m-cohort vs 7.60 m (95%CI 4.13-30.5) for wt-cohort, p 0.0179), whereas in the CT-IO arm there were no differences among the two groups (mPFS 6.77 m(95%CI5.17-NA) for m-cohort vs 7.03 m (95%CI 5.73-8.43) for wt-cohort, p 0.567).
Conclusions
IO based treatments are not detrimental for pts harboring novel driver alterations per se. Anyway, in this particular subset of patients, IO single agent may not be effective enough and combination treatment with chemotherapy might be recommended regardless of PD-L1 expression.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Prelaj: Financial Interests, Personal, Training: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Other, Travel grant: Roche; Financial Interests, Personal, Other, Travel accommodation: Italfarma. R. Ferrara: Financial Interests, Personal, Advisory Board: BeiGene, MSD. C. Proto: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, MSD; Financial Interests, Personal, Invited Speaker: Bristol Meyer Squibb; Financial Interests, Institutional, Principal Investigator: Janssen, Pfizer, Lilly, Spectrum Pharmaceuticals, Roche, MSD, BMS, AstraZeneca. G. Lo Russo: Financial Interests, Personal, Advisory Role: BMS, Italfarmaco, Roche, Pfizer; Financial Interests, Personal, Invited Speaker: MSD, Novartis, AstraZeneca, Sanofi. M.C. Garassino: Financial Interests, Personal, Advisory Role: AstraZeneca, MSD, International GmbH, BMS, Boehringer Ingelheim Italia S.p.A., Celgene, Eli lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda. F.G.M. De Braud: Financial Interests, Personal, Advisory Board: Ignyta, BMS, Daiichi Sankyo, Pfizer, Octimet Oncology, Incyte, Teofarma, Pierre Fabre, Roche, EMD Serono, Sanofi, NMS Nerviano Medical Science, Pharm Research Associated (U.K.) Ltd; Financial Interests, Personal, Invited Speaker: BMS, Roche, MSD, Ignyta, Bayer, ACCMED, Dephaforum S.r.l., Nadirex, Merck, Biotechspert Ltd, PriME Oncology, Pfizer, Servier, Celgene, Tesaro, Loco Oncology Inc, Sanofy, Healthcare Research & Pharmacoepidemiology; Financial Interests, Institutional, Principal Investigator: Novartis, Roche, BMS, Celgene, Incyte, NMS, Merck KGAA, Pfizer, Tesaro, MSD. All other authors have declared no conflicts of interest.