Analysis of the association between prior chemotherapy regimens and outcomes of subsequent anti-PD-(L)1 monotherapy in advanced non-small cell lung cancer

Abstract

Background: Immune checkpoint inhibitor (ICI) monotherapy targeting PD-1/PD-L1 has been a prominent option for the patients with advanced non-small cell lung cancer (NSCLC), which is now commonly used in second- or later-line settings after the failure of conventional chemotherapy. Chemotherapy can modulate tumor immunity in drug-dependent manner, suggesting pre-ICI chemotherapeutic regimens might influence the efficacy of immunotherapy. Therefore, it is of interest to investigate the associations between the types of pre-ICI chemotherapy and the outcomes of patients receiving ICIs treatment. Methods: The data from NSCLC patients who received anti-PD-1/PD-L1 ICI monotherapy after the failure of first-line chemotherapy were retrospectively reviewed. Clinical outcomes of the patients following ICIs monotherapy were compared according to different pre-ICI chemotherapeutic regimens. Results: Eighty-nine cases receiving ICI monotherapy immediately after the failure of first-line chemotherapy were included into final analysis. The patients in Gem group had the longest PFS (median: 6.50 m) following ICIs treatment (P=0.031), compared to Pem group and Tax group (median: 3.49 and 3.30 m, respectively). Pre-ICI chemotherapy with Gem retained independently associated with favorable PFS (P=0.014, HR 0.52; 95% CI, 0.31-0.88) in multivariate analysis after adjusting for other covariates. The patients in Gem group also achieved better objective response rate (ORR) (P=0.046) and disease control rate (DCR) (P=0.005) following ICIs treatment compared to those in Pem/Tax group. The differences in depth of response to ICIs between Gem and Pem/Tax groups were also compared. Of the 48 patients who achieved controlled disease and had ≥1 measurable target lesion during ICIs treatment, no greater tumor shrinkage was observed in Gem group (P=0.374), however, Gem group trended to have shorter TTM (P=0.074). Conclusions: Prior-line chemotherapy regimens might influence outcomes of the following ICIs monotherapy. Patients received pre-ICI gemcitabine-containing chemotherapy are significantly correlated with longer PFS and better response to ICIs treatment.