Nivolumab with or without Docetaxel for Patients with Previously Treated Advanced or Recurrent NSCLC: Results from the Phase 2/3 TORG1630 Trial

Immune checkpoint inhibitor (ICI) monotherapy is currently a standard second-line treatment option for patients with non–small-cell lung cancer (NSCLC). However, studies demonstrated that adding cytotoxic chemotherapy to ICI therapy may improve the treatment outcomes.¹

This multi-institutional, open-label, randomized phase 2/3 trial compared the efficacy of nivolumab monotherapy (arm A) with nivolumab plus docetaxel (arm B) in patients with previously treated ICI-naïve NSCLC. The enrolled patients were prestratified based on tumor histology, sex, and driver mutations.¹

The primary end point was the superiority of nivolumab plus docetaxel over nivolumab monotherapy in improving overall survival (OS) in the phase 3 part of the trial. The study was started in November 2017; however, the patients’ accrual was discontinued due to the approval of ICIs in the first-line setting in late 2018.

Of the enrolled patients, 128 were eligible for analysis. Patients’ demographics were well-balanced in both arms. The median OS was 14.7 months (95% confidence interval [CI], 11.4-18.7) in arm A and 23.1 months (95% CI, 16.7-not reached) in arm B. The hazard ratio (HR) of OS was 0.63 favoring nivolumab plus docetaxel (90% CI, 0.42-0.95; P = .0310). In arms A and B, the median PFS was 3.1 months (95% CI, 2.0-3.9) and 6.7 months (95% CI, 3.8-9.4), respectively. The HR for PFS was 0.58 favoring nivolumab plus docetaxel (95% CI, 0.39-0.88; P = .0095). The overall response rate (ORR) was 14.0% (95% CI, 6.3-25.8) in arm A and 41.8% (95% CI, 28.7-55.9) in arm B (P = .0014). Subgroup analyses of OS showed that the HRs also favored arm B over arm A across subgroups treated with the combination regimen, including all PD-L1 expression levels, smoking status, pathological type, metastasis site, tumor mutational burden, and prior therapy. Patients in arm B with EGFR-mutant tumors had higher median OS compared with arm A (11.0 months in arm A; 95% CI, 3.5-14.0; vs 20.6 months in arm B; 95% CI, 5.8-not reached; HR, 0.45; 95% CI, 0.17-1.17).

Patients in arm B experienced more hematologic toxicity and gastrointestinal adverse events compared with those in arm A. In addition, adverse events leading to treatment discontinuation were more common among patients in arm B compared with arm A (39.1% vs 9.4%). Moreover, 2 treatment-related deaths were reported: 1 from pneumonitis in arm A and 1 from myocarditis in arm B.

The investigators concluded that the combination of nivolumab plus docetaxel in the second-line treatment of patients with NSCLC improved OS, PFS, and ORR compared with nivolumab monotherapy, despite a slightly higher risk of toxicity. Importantly, this is the first randomized clinical trial to demonstrate the significant survival benefit of combining chemotherapy and ICI compared with ICI monotherapy in any cancer type.

Reference

1. Kawashima Y, Taniguchi Y, Shimokawa T, et al. A randomized phase II/III trial of nivolumab versus nivolumab plus docetaxel for previously treated advanced or recurrent non–small cell lung cancer: TORG1630. Presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 9030.