Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L)

Abstract

BackgroundStudies have suggested that chemotherapy after immune checkpoint inhibitors may confer an improved response for non–small cell lung cancer (NSCLC). However, potential selection bias in such studies has not been addressed. We therefore applied propensity score analysis to investigate the efficacy of chemotherapy after PD-1 inhibitor treatment (CAP) compared with chemotherapy alone.MethodsWe conducted a retrospective observational cohort study for patients treated at 47 institutions across Japan between April 1, 2014 and July 31, 2017. Eligible patients had advanced or recurrent NSCLC who have undergone chemotherapy. Patients subsequently treated with chemotherapy (docetaxel with or without ramucirumab, S-1 or pemetrexed) either after PD-1 inhibitor therapy (CAP cohort) or alone (control cohort) were included. The primary end point was objective response rate (ORR). Inverse probability weighting (IPW) was applied to adjust for potential confounding factors.ResultsA total of 1439 patients (243 and 1196 in the CAP and control cohorts, respectively) was available for unadjusted analysis. Several baseline characteristics—including age, histology,EGFRorALKgenetic alterations, and brain metastasis—differed significantly between the two cohorts. After adjustment for patient characteristics with the IPW method, ORR was 18.9% for the CAP cohort and 11.0% for the control cohort (ORR ratio 1.71; 95% CI 1.19 to 2.46; p=0.004). IPW-adjusted Kaplan-Meier curves showed that median progression-free survival (PFS) for the CAP and control cohorts was 2.8 and 2.7 months (IPW-adjusted HR 0.95; 95% CI 0.80 to 1.12; p=0.55), and median overall survival (OS) was 9.2 and 10.4 months (IPW-adjusted HR 1.05; 95% CI 0.86 to 1.28; p=0.63), respectively.ConclusionsAfter accounting for selection bias by propensity score analysis, CAP showed a significantly higher ORR compared with chemotherapy alone, with the primary end point of ORR being achieved. However, these results did not translate into a PFS or OS advantage, suggesting that prior administration of PD-1 inhibitors may result in a synergistic antitumor effect with subsequent chemotherapy, but that such an effect is transient. CAP therefore does not appear to achieve durable tumor control or confer a lasting survival benefit.

Real‐world efficacy of atezolizumab in non‐small cell lung cancer: A multicenter cohort study focused on performance status and retreatment after failure of anti‐PD‐1 antibody

“…A recent study (WJOG10217L) demonstrated higher ORR of chemotherapy after PD‐1 inhibitor treatment (CAP) compared with chemotherapy alone. OS of CAP in patients was 10.4 months 11 . In our study, OS (12.8 months) was compatible with WJOG10217L.…”

Efficacy of Docetaxel Plus Ramucirumab as Palliative Third-Line Therapy Following Second-Line Immune-Checkpoint-Inhibitor Treatment in Patients With Non-Small-Cell Lung Cancer Stage IV

“… 22 Very recently, 2 studies from Japan performed a propensity score weighted analysis of R + D after ICI treatment in NSCLC patients to investigate the effect of this sequence in comparison to a control group without PD-1/PD-L1-directed therapy. 23 , 24 While Kato et al described a benefit for the ICI pretreated cohort in terms of ORR, but not for outcome parameters, Tozuka et al in contrast showed a significant increase in PFS, 5.9 months versus 2.8 months (in the control group); P = 0.03, and a trend toward an improved OS for the ICI pretreated cohort. Further details of all mentioned R + D third-line studies are presented in Table 4 .…”

Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study

“…However, since cetuximab remains a key chemotherapy drug for R/M SCCHN, it is expected that cetuximab is increasingly used as a second- or later-line setting after exposure to immunotherapy. Several studies have demonstrated potential improvements in the treatment outcomes of cytotoxic chemotherapy after exposure to immunotherapy in various types of malignancies, including malignant melanoma, non-small cell lung cancer and stomach cancer [ 7 – 9 ]. In R/M SCCHN, two retrospective studies assessed patients who progressed on ICIs and subsequently underwent cytotoxic chemotherapy; these studies reported a relatively higher overall response rate (ORR) [ 10 , 11 ].…”