Some previous studies showed chemo-resistance was associated with upregulation of programmed cell death ligand 1 (PD-L1) and mutation burden in NSCLC. Recently, immune checkpoint inhibitors are available to treat NSCLC, whereas efficacy of immune checkpoint inhibitor in patients showing early progression to first-line cytotoxic chemotherapy remains unknown.
We retrospectively collected medical records of advanced NSCLC patients who received second-line nivolumab treatment after cytotoxic chemotherapy in our hospital. Early progression was defined as exacerbation less than 16 weeks from the initiation of first-line chemotherapy. The patients were divided according to time to progression (TTP) of first-line therapy for <16, and ≥16weeks and were evaluated efficacy of second-line nivolumab.
Fifty-one patients were received nivolumab treatment as second-line therapy after first-line line cytotoxic chemotherapy failure from February 2016 to April 2017, 22 patients were in the TTP <16 weeks group and 29 patients were in the TTP ≥16 weeks group. The median TTP of first-line cytotoxic chemotherapy was 17.0 weeks (95% CI 8.0-23.1 weeks). The median progression-free survival (PFS) of second-line nivolumab was 6.7 months (95% CI 3.2 -11.2 months). The median PFS was 11.3 months in the TTP <16 weeks group versus 3.7 months in the TTP ≥16 weeks group (hazard ratio, 0.44; 95% CI, 0.21–0.88, P = 0.019). The objective response rate was 55% versus 18% (P = 0.005) and the complete response rate was 5% vs 0%. The median overall survival was not reached and 11.3 months, respectively (hazard ratio, 0.68; 95% CI, 0.30–1.46, p = 0.32). On multivariate analysis, TTP <16 weeks (hazard ratio, 0.39; 95% CI, 0.17-0.83, p = 0.015) and non-sq histology (hazard ratio, 0.33; 95% CI, 0.16-0.69, p = 0.004) were significantly favorable factors for PFS.
Among patients with advanced NSCLC that had early progressed during or after primary cytotoxic chemotherapy, nivolumab was effective as second-line therapy.
Clinical trial identification
Legal entity responsible for the study
National Cancer Center Hospital East.
Has not received any funding.
H. Udagawa: Honoraria: Ono, Bristol-Myers Squibb, MSD, Taiho, Chugai, AstraZeneca and Amco. S. Umemura: Honoraria: Ono. S. Matsumoto: Honoraria: Ono, Bristol-Myers Squibb. S. Niho: Honoraria: Bristol-Myers Squibb. K. Goto: Grant: Ono; Honoraria: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.