Continuous Versus 1-Year Fixed-Duration Nivolumab in Previously Treated Advanced Non-Small-Cell Lung Cancer: CheckMate 153

Abstract

Purpose: Limited data exist on the optimal duration of immunotherapy, including for non-small-cell lung cancer (NSCLC). We present an exploratory analysis of CheckMate 153, a largely community-based phase IIIb/IV study, to evaluate the impact of 1-year fixed-duration versus continuous therapy on the efficacy and safety of nivolumab.

Methods: Patients with previously treated advanced NSCLC received nivolumab monotherapy (3 mg/kg every 2 weeks). Those still receiving treatment at 1 year, including patients perceived to be deriving benefit despite radiographic progression, were randomly assigned to continue nivolumab until disease progression or unacceptable toxicity or to stop nivolumab with the option of on-study retreatment after disease progression (1-year fixed duration).

Results: Of 1,428 patients treated, 252 were randomly assigned to continuous (n = 127) or 1-year fixed-duration (n = 125) treatment (intent-to-treat [ITT] population). Of these, 89 and 85 patients in the continuous and 1-year fixed-duration arms, respectively, had not progressed (progression-free survival [PFS] population). With minimum post-random assignment follow-up of 13.5 months, median PFS was longer with continuous versus 1-year fixed-duration treatment (PFS population: 24.7 months v 9.4 months; hazard ratio [HR], 0.56 [95% CI, 0.37 to 0.84]). Median overall survival from random assignment was longer with continuous versus 1-year fixed-duration treatment in the PFS (not reached v 32.5 months; HR, 0.61 [95% CI, 0.37 to 0.99]) and ITT (not reached v 28.8 months; HR, 0.62 [95% CI, 0.42 to 0.92]) populations. Few new-onset treatment-related adverse events occurred. No new safety signals were identified.

Conclusion: To our knowledge, these findings from an exploratory analysis represent the first randomized data on continuous versus fixed-duration immunotherapy in previously treated advanced NSCLC and suggest that continuing nivolumab beyond 1 year improves outcomes.

FIG 1.

CONSORT diagram of patient disposition. AE, adverse event; CR, complete response; ITT, intent-to-treat; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease. (*) The ITT population comprised all patients who continued to receive treatment at 1 year (y) and were randomly assigned, regardless of response status. (†) Random assignment took place after 1 year of treatment with nivolumab. (‡) Patients were treated beyond progression. (§) The post–random assignment PFS population comprised patients who did not have PD and had not initiated other systemic anticancer therapy before random assignment.

FIG 2.

Progression-free survival (PFS) from random assignment (A) in the PFS population, (B) in patients with complete response/partial response, and (C) in patients with stable disease. Random assignment took place after 1 year of treatment with nivolumab; the post–random assignment PFS population comprised patients who did not have progressive disease (PD) and had not initiated other systemic anticancer therapy before random assignment. Minimum follow-up after random assignment in the intent-to-treat population was 13.5 months overall; median follow-up times after random assignment in the PFS population were 40.5 months and 35.2 months for the continuous arm and 1-year fixed-duration treatment arm, respectively. HR, hazard ratio. (*) Optional retreatment allowed at PD.

FIG 3.

Multivariable analysis of progression-free survival (PFS) since random assignment by subgroup in the PFS population. Random assignment took place was after 1 year of treatment with nivolumab; the post–random assignment PFS population comprised patients who did not have progressive disease and had not initiated other systemic anticancer therapy before random assignment. Minimum follow-up after random assignment in the intent-to-treat population was 13.5 months overall; median follow-up times after random assignment in the PFS population were 40.5 months and 35.2 months for the continuous and 1-year fixed-duration treatment arms, respectively. A multivariable Cox proportional hazards regression analysis for PFS was also performed, whereby the effect of treatment arm was adjusted for key baseline characteristics as well as response/progression status at random assignment; the adjusted hazard ratio was 0.55 (95% CI, 0.36 to 0.85). (a) Optional retreatment was allowed at PD. CR, complete response; NA, not available; NR, not reached; PD-L1, programmed death ligand 1; PR, partial response; SD, stable disease. (*) Hazard ratio not calculated because of the small sample size.

FIG 4.

Overall survival (OS) from random assignment in (A) the intent-to-treat (ITT) population, (B) the progression-free survival (PFS) population, (C) patients with complete response/partial response (CR/PR; PFS population), (D) patients with stable disease (SD) at random assignment (PFS population), and (E) patients with progressive disease (PD) before random assignment (ITT population). Random assignment took place after 1 year (y) of treatment with nivolumab. The ITT population comprised all patients who continued to receive treatment at 1 year and were randomly assigned, regardless of response status. The post–random assignment PFS population comprised patients who did not have PD and had not initiated other systemic anticancer therapy before random assignment. Minimum follow-up after random assignment in the ITT population was 13.5 months overall; median follow-up times after random assignment in the ITT population were 39.8 months and 34.4 months for the continuous and 1-year fixed-duration treatment arms, respectively; median follow-up times after random assignment in the PFS population were 40.5 months and 35.2 months for the continuous and 1-year fixed-duration treatment arms, respectively. HR, hazard ratio; NR, not reached. (*) Optional retreatment allowed at PD.

FIG 5.

Initiation and duration of nivolumab retreatment in patients in the progression-free survival population who progressed after random assignment. (*) Patient was last reported as progression free and had one dose during retreatment. (†) Patient had one dose during retreatment. (‡) Patient had confirmed disease progression after beginning retreatment; patient had one dose during retreatment. (§) Two additional patients with ongoing retreatment had progressive disease (PD) before random assignment.