Clinical outcomes of ramucirumab plus docetaxel in the treatment of patients with non-small cell lung cancer after immunotherapy: a systematic literature review

Abstract

Introduction: In the REVEL trial, ramucirumab plus docetaxel demonstrated significant improvements in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) compared with placebo plus docetaxel for treatment of metastatic non-small cell lung cancer (NSCLC) that progressed during or after platinum-based chemotherapy. Since the approval of ramucirumab plus docetaxel, immune checkpoint inhibitors (ICIs), either as single agents or in combination with chemotherapy, have become the standard of care for first-line treatment of patients with advanced NSCLC. However, efficacy and safety data for ramucirumab plus docetaxel after prior ICI treatment from randomized controlled clinical studies are lacking.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature review was performed. Electronic databases and select international oncology conference proceedings were searched. Studies published between 01 January 2014 and 01 July 2022, which evaluated 2 efficacy outcomes (and included at least 1 time-to-event endpoint) or safety outcomes of ramucirumab plus docetaxel in NSCLC that progressed after prior ICI treatment, were identified. Twelve studies were included in the analysis. Two treatment groups were selected: ramucirumab plus docetaxel after prior ICI ± chemotherapy (RAM + DTX ICI pre-treated) and ramucirumab plus docetaxel after prior chemotherapy only (RAM + DTX ICI naïve). OS, PFS, ORR, disease control rate (DCR), and safety data were extracted and descriptively summarized across both treatment groups.

Results: The pooled weighted median PFS and median OS were 5.7 months (95% confidence interval [CI]: 3.9-6.8) and 11.2 months (95% CI: 7.5-17.5), respectively, in the RAM + DTX ICI pre-treated group and 3.8 months (95% CI: 2.3-4.1) and 13.5 months (95% CI: 8-24.0), respectively, in the RAM + DTX ICI naïve group. The ORR and DCR ranged from 20.9% to 60.0% and from 62.4% to 90.0%, respectively, in the RAM + DTX ICI pre-treated group and from 17.7% to 20.0% and from 57.1% to 75.0%, respectively, in the RAM + DTX ICI naïve group. The safety profile across studies was consistent between both treatment groups, and no new safety signals were reported.

Conclusions: Cumulatively, these results support the combination of ramucirumab plus docetaxel as an effective and safe subsequent therapy for the treatment of patients with metastatic NSCLC with disease progression irrespective of previous ICI treatment.

Keywords: antiangiogenic therapy; docetaxel; immune checkpoint inhibitors; non-small cell lung cancer; ramucirumab.

Figure 1

PRISMA flow diagram for article selection. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for the systematic review, detailing the database searches and the number of studies screened and included for final analysis. *Outcomes that were not of interest included 12-month overall survival rate and time to treatment discontinuation. DTX, Docetaxel; HEOR, Health economics and outcomes research; ICI, Immune checkpoint inhibitor; n, Number of patients; RAM, Ramucirumab.

Figure 2

Efficacy endpoints across studies in RAM + DTX ICI pre-treated and ICI naïve patients. (A) Median progression-free survival; (B) Median overall survival; (C) Overall response rate; and (D) Disease control rate. Red bars indicate the RAM+DTX ICI pre-treated group and brown bars the RAM+DTX ICI naïve group. CI, Confidence interval; DTX, Docetaxel; ICI, Immune checkpoint inhibitor; n, Number of patients; NE, Not estimable; RAM, Ramucirumab.

Figure 3

Pooled adverse events of any grade and grade ≥3 in RAM + DTX ICI pre-treated and naïve groups. The percentage of any-grade AEs were calculated based on the cumulative safety population for the RAM + DTX ICI pre-treated group (493 patients) and RAM + DTX ICI naïve group (341 patients), while the percentages of grade ≥3 AEs were calculated based on the 321 patients in the RAM + DTX ICI pre-treated group and 115 patients in the RAM + DTX ICI naïve group. This difference was because the Chen et al. study did not contribute grade ≥3 AEs to the data pooling due to the absence of published data in the manuscript. DTX, Docetaxel; ICI, Immune checkpoint inhibitor; RAM, Ramucirumab.