1336P - Small cell transformation in EGFR-mutated non-small cell lung cancer (EGFR+ NSCLC): Efficacy of immune checkpoint inhibitors or tyrosine kinase inhibitors combined with platinum-based chemotherapy

Background

Given the broad application of 3^rd generation tyrosine kinase inhibitors (TKI) as standard 1^st line treatment for EGFR+ NSCLC, small cell transformation (SCT) as a mechanism of adaptive resistance is seen more frequently. Little is known about optimal treatment strategies and prognosis is generally poor in this subset of patients.

Methods

We conducted a retrospective study on the efficacy of different treatment strategies: platinum-based chemotherapy alone (C) vs. immune checkpoint inhibitors in combination with C (ICI+C) vs. tyrosine kinase inhibitors in combiation with C (TKI+C) in patients with EGFR+ NSCLC and SCT treated at 19 centers in Europe and the United States.

Results

Of a total of 40 patients, 16 received ICI+C, 9 TKI+C, and 15 C alone as first treatment after SCT. Median time from TKI initiation to SCT was 22 months. Half of the patients (48%) presented with brain metastases at the time of SCT. Overall response rate was 54% for ICI+C, 60% for TKI+C, and 46% for C alone. Median progression-free survival (PFS) was 5 months (95% confidence interval [CI] 3.2-6.8) for ICI+C, 6 months (CI 3.6-8.4) for TKI+C, and 4 months (CI 3.4-4.6) for C alone. Median overall survival (OS) from first SCT treatment was 18 months (CI 8.9-27.1) for ICI+C, 11 months (CI 9.8-12.1) for TKI+C, and 8 months (CI 5.3-10.6) for C alone. EGFR L858R subtype was associated with improved OS (Hazard ratio 0.31 [CI 0.11-0.85]). The impact of follow-up therapies will be presented at the conference. Table: 1336P

Conclusions

Although limited by its retrospective nature, our data suggest that combination therapies, ICI+C in particular, might be superior to C alone in EGFR+ NSCLC with SCT.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Deutsche Krebshilfe, National Network Genomic Medicine Lung Cancer (nNGM).

Disclosure

F.C. Saalfeld: Financial Interests, Personal, Invited Speaker: Janssen, Takeda, Pfizer, AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodation: Lilly; Financial Interests, Personal, Advisory Role: Janssen, AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Writing Engagements: Thieme. M. Wiesweg: Financial Interests, Personal, Invited Speaker: Amgen, Roche, Takeda, GSK, AstraZeneca; Financial Interests, Personal, Expert Testimony: GSK; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Roche, Janssen, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Takeda; Financial Interests, Institutional, Funding: Bristol Myers Squibb. J. Alt: Financial Interests, Advisory Board: AstraZeneca, MSD, Novartis, Roche, BMS, Janssen, Merck; Financial Interests, Invited Speaker: AstraZeneca, BMS, Roche, Boehringer Ingelheim. F. Griesinger: Financial Interests, Invited Speaker, & Advisory: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, AbbVie, Tesaro/GSK, Siemens, Tesaro, Amgen, Sanofi, Daiichi Sankyo, BeiGene. D. Kauffmann-Guerrero: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Invited Speaker: Boehringer Ingelheim, Roche, MSD, Pfizer, BMS, GSK, Novartis, Takeda, Sanofi, Janssen; Financial Interests, Other, Travel Grant / Congress Fees: Takeda, Boehringer Ingelheim. T.R. Overbeck: Financial Interests, Invited Speaker, & Adisory: AstraZeneca; Financial Interests, Invited Speaker: Boehringer Ingelheim, Roche. C. Wesseler: Financial Interests, Invited Speaker: Eli Lilly, AstraZeneca, Roche, BMS, Merck, MSD, Merck, Takeda, Pfizer, Amgen, Boehringer Ingelheim, Sanofi, Novartis, GSK. O.M. Illini: Financial Interests, Invited Speaker: Boehringer Ingelheim, Eli Lilly, Menarini, Merck Sharp & Dohme, Pfizer, Roche; Financial Interests, Advisory Board: Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche. S.I. Rothschild: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Bayer, Takeda, Sanofi Aventis, Roche Diagnostics, Roche Pharma, PharmaMar, Pfizer, Otsuka, Novartis, MSD, Merck Serono, Eli Lilly, Eisai, Boehringer Ingelheim, BMS; Financial Interests, Research Grant: Amgen, Roche, Merck, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Amgen, Takeda, Roche Diagnostics, Roche Pharma, Novartis, MSD Oncology, BMS, AstraZeneca; Financial Interests, Institutional, Expert Testimony: AstraZeneca, Roche Pharma, BMS; Financial Interests, Institutional, Other, Support for travel and accommodations: Amgen, Takeda, Roche, MSD, Eli Lilly, BMS, AstraZeneca; Non-Financial Interests, Member of Board of Directors: Swiss Group for Clinical Cancer Research (SAKK); Non-Financial Interests, Member: Federal Drug Commission of the Federal Office of Public Health. P. Christopoulos: Financial Interests, Sponsor/Funding: Amgen, AstraZeneca, Boehringer Ingelheim, Novartis, Roche, Takeda; Financial Interests, Invited Speaker, &Advisory Board: AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, Takeda. M. Wermke: Financial Interests, Personal, Invited Speaker: Lilly, Boehringer Ingelheim, Synlab, Janssen, Merck Serono, GWT TUD, Amgen, Novartis; Financial Interests, Advisory Board: Bristol Myers Squibb, Novartis, Boehringer Ingelheim, ISA Pharmaceuticals, Immatics, Bayer, ImCheck Therapeutics; Financial Interests, Research Grant: Roche; Financial Interests, Other, Travel&Accommodation: Pfizer, Bristol Myers Squibb, AstraZeneca, Amgen, GEMoaB, Sanofi/Aventis, Immatics, Merck Serono. All other authors have declared no conflicts of interest.