Abstract 661P
Background
The role of re-treatment with immune checkpoint inhibitors (ICI) following progression on prior chemotherapy and ICI (chemo-ICI) in patients with NSCLC remains unclear, with heterogeneous outcomes reported mainly from retrospective studies. Prospective studies are necessary to evaluate the efficacy and prognostic factors of ICI re-treatment.
Methods
This prospective, multi-institutional, observational study in Japan (trial number: UMIN000038413) enrolled patients with advanced NSCLC who relapsed after chemo-ICI. Patients received ICI monotherapy (nivolumab, pembrolizumab, atezolizumab) until disease progression. The primary endpoint was overall response rate (ORR) and secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety, and efficacy in key subgroups (type of prior ICI: anti-PD-1/anti-PD-L1, and other exploratory factors).
Results
Forty patients were enrolled, with thirty-eight included in the analysis. The ORR for ICI monotherapy was 10.5% (95% confidence interval [CI], 2.9-24.8%), with one complete response and three partial responses observed. Median PFS and OS were 2.5 months (95%CI: 1.6-4.0 months) and 9.9 months (95%CI: 8.0-13.6 months), respectively. The estimated 1-year and 2-year PFS rates were same at 13.8%. In an exploratory multivariate analysis, a longer ICI-free interval (>1 year) and prior anti-PD-L1 therapy were prognostic factors for PFS (Hazard ratio: 0.33, p=0.009, 0.33, p=0.02, respectively). PFS was longer in patients with prior anti-PD-L1 therapy who received anti-PD-1 re-treatment, compared to those with prior anti-PD-1 therapy and anti-PD-L1 re-treatment (log-rank, p=0.037). The safety profile included 2.6% grade 3 rash and myositis, with 2.6% experiencing treatment discontinuation due to toxicity.
Conclusions
This prospective study demonstrated a modest response to ICI re-treatment with a small population achieving long-term PFS. Further studies are warranted to identify the subgroup that benefits from ICI re-treatment.
Clinical trial identification
UMIN000038413; 2019/11/01.
Editorial acknowledgement
Legal entity responsible for the study
North Japan Lung Cancer Study Group (NJLCSG).
Funding
Has not received any funding.
Disclosure
H. Tanaka: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical, Takeda, Ono Pharmaceutical, Bristol Myers Squibb, Boehringer-Ingelheim Japan, Pfizer Japan Inc, Amgen. Y. Kawashima: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly and Company, Kyowa Kirin, Life Technologies Japan. N. Yoshimura: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly and Company, Kyowa Kirin, Boehringer-Ingelheim Japan, MSD, Nippon Kayaku, Takeda, GSK, Thermo Fisher Scientific Life Technologies Japan, Novartis. Y. Tsukita: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly and Company, Bristol Myers Squibb, Boehringer-Ingelheim Japan, MSD, Eisai, Daiichi Sankyo, AstraZeneca. T. Nakagawa: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical, Ono Pharmaceutical, Novartis Pharma, Merck and CO, Pfizer Japan Inc, Nippon Kayaku, Eli Lilly Japan. M. Inomata: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical, Novartis, Ono Pharmaceutical, Bristol Myers Squibb, Boehringer-Ingelheim Japan, Pfizer Japan Inc, Amgen, Daiichi Sankyo, MSD, GSK. S. Sugawara: Financial Interests, Personal, Other, Lecture fee: AstraZeneca, Chugai Pharma, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Ono Pharmaceutical, MSD K.K, Kyowa Kirin, Takeda, Nippon Kayaku, Merck, Amgen, Thermo Fisher Scientific; Financial Interests, Personal, Other, Lecture Fee: Eisai, Sysmex; Financial Interests, Institutional, Local PI: AstraZeneca, Chugai Pharma, MSD K.K, Daiichi Sankyo, Bristol Myers Squibb, AnHeart, Ono Pharmaceutical, Nippon Boehringer Ingelheim, AbbVie, Parexel International, Amgen, Taiho Pharmaceutical, Accerise, A2 Healthcare, EPS Corporation, Syneos Health, PPD-SNBL. All other authors have declared no conflicts of interest.