Abstract 1224P
Background
EGFR exon 20 insertion (ex20ins) mutations are rare, and data on clinical outcomes with immunotherapy (IO) in these patients are scarce. Per National Comprehensive Cancer Network guidelines, IO monotherapy is not recommended over targeted therapies for non–small cell lung cancer (NSCLC) patients with an oncogenic driver. To determine the efficacy of IO monotherapy in the second-line setting and beyond (≥2nd-line) for EGFRex20ins+ NSCLC, we conducted a systematic review and meta-analysis of real-world objective response rate (ORR) data.
Methods
We analyzed ORRs of ≥2nd-line IO monotherapies in EGFRex20ins+ NSCLC from: (1) PubMed literature search for clinical studies reporting ORR, disease control rate (DCR), or progression-free survival (PFS); (2) longitudinal data from the United States Flatiron Health Research Database; (3) a retrospective chart review from 12 German oncology centers; and (4) prior anticancer therapy and associated response data from a single-arm, phase I/II study of mobocertinib, an oral EGFR tyrosine kinase inhibitor targeting EGFRex20ins, in EGFRex20ins+ NSCLC patients previously treated with ≥2nd-line IO.
Results
From the meta-analysis of all data, the calculated ORR [95% confidence intervals] for ≥2nd-line IO monotherapy in patients with EGFRex20ins+ NSCLC was 3.5% [0.6%, 9.9%] (Table). Across sources (N=91), reported ORRs ranged from 0% to 14.3% (1/7 patients in single study), with 2 total responses; DCRs ranged from 23.8% to 30.0%, and median PFS ranged from 2.3 months to 4.0 months. Reported data were limited by small number of patients and studies reporting mixed lines of therapy (≥2nd-line). Table: 1224P
| Data source | Reported ORR, n/N (%) |
| Takeda M. (Oncotarget. 2018) | 1/7 (14.3%) |
| LC-SCRUM-JAPAN/Udagawa (J Thorac Oncol. 2019) | 0/21 (0%) |
| Yang G. (Lung Cancer. 2020) | 0/2 (0%) |
| Flatiron database | 1/20 (5%) |
| German chart review | 0/10 (0%) |
| Mobocertinib study | 0/31 (0%) |
| Meta-analysis | Mean ORR [2.5%, 97.5%] |
| 3.5% [0.6%, 9.9%] |
Conclusions
Results of this meta-analysis suggest that IO monotherapies are not effective in the ≥2nd-line setting for patients with EGFRex20ins+ NSCLC, which further highlights the need for novel treatment options in this population.
Clinical trial identification
Editorial acknowledgement
Professional medical writing assistance was provided by Amy Zannikos, PharmD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Millennium Pharmaceuticals, Inc.
Legal entity responsible for the study
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Funding
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Disclosure
P. Christopoulos: Financial Interests, Personal, Other, Research funding: AstraZeneca, Novartis, Roche, Takeda; Financial Interests, Personal, Other, advisory board/lecture fees: AstraZeneca, Boehringer Ingelheim, Chugai, Novartis, Pfizer, Roche, Takeda. S.I. Ou: Financial Interests, Personal, Other, Personal fees: Pfizer, AstraZeneca, Takeda/ARIAD, Roche/Genentech, Daiichi Sankyo, Janssen/Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Turning Point Therapeutics, Elevation Oncology. J. Lin: Financial Interests, Personal, Full or part-time Employment: Takeda. D. Berg: Financial Interests, Personal, Full or part-time Employment: Takeda. J. Hong: Financial Interests, Personal, Full or part-time Employment: Takeda. Y. Yin: Financial Interests, Personal, Full or part-time Employment: Takeda. J. Lin: Financial Interests, Personal, Full or part-time Employment: Takeda. V. Bunn: Financial Interests, Personal, Full or part-time Employment: Takeda. H.M. Lin: Financial Interests, Personal, Full or part-time Employment: Takeda. M. Mehta: Financial Interests, Personal, Full or part-time Employment: Takeda. M. Thomas: Financial Interests, Personal, Other, Honoraria: AbbVie, BMS, MSD, AstraZeneca, Novartis, Roche, Takeda, Lilly, Chugai, Celgene, Boehringer Ingelheim, Pfizer, Janssen; Financial Interests, Personal, Other, travel: AbbVie, BMS, MSD, AstraZeneca, Novartis, Roche, Takeda, Lilly, Chugai, Celgene, Boehringer Ingelheim, Pfizer; Financial Interests, Personal, Advisory Role: AbbVie, BMS, MSD, AstraZeneca, Novartis, Roche, Takeda, Lilly, Chugai, Celgene, Boehringer Ingelheim, Pfizer, Janssen; Financial Interests, Institutional, Other, Research funding: BMS, AstraZeneca, Roche, Takeda.