Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer

Abstract

Background: Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.

Methods: In this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non-small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival.

Results: Overall survival was longer with nivolumab than with docetaxel. The median overall survival was 12.2 months (95% confidence interval [CI], 9.7 to 15.0) among 292 patients in the nivolumab group and 9.4 months (95% CI, 8.1 to 10.7) among 290 patients in the docetaxel group (hazard ratio for death, 0.73; 96% CI, 0.59 to 0.89; P=0.002). At 1 year, the overall survival rate was 51% (95% CI, 45 to 56) with nivolumab versus 39% (95% CI, 33 to 45) with docetaxel. With additional follow-up, the overall survival rate at 18 months was 39% (95% CI, 34 to 45) with nivolumab versus 23% (95% CI, 19 to 28) with docetaxel. The response rate was 19% with nivolumab versus 12% with docetaxel (P=0.02). Although progression-free survival did not favor nivolumab over docetaxel (median, 2.3 months and 4.2 months, respectively), the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel (19% and 8%, respectively). Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (≥1%, ≥5%, and ≥10%) of the PD-1 ligand. Treatment-related adverse events of grade 3 or 4 were reported in 10% of the patients in the nivolumab group, as compared with 54% of those in the docetaxel group.

Conclusions: Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy, overall survival was longer with nivolumab than with docetaxel. (Funded by Bristol-Myers Squibb; CheckMate 057 ClinicalTrials.gov number, NCT01673867.).

Fig. 1. Efficacy of nivolumab versus docetaxel in patients with advanced non-squamous NSCLC

Data are based on a March 18, 2015 database lock. (A) Kaplan-Meier plot of overall survival. All randomized patients (nivolumab, n = 292; docetaxel, n = 290). Symbols represent censored observations. (B) Treatment effect on overall survival in pre-defined subsets. All randomized patients (nivolumab, n = 292; docetaxel, n = 290). HR was not computed for other subsets with less than 10 patients per treatment group. (C) Characteristics of response and progression as assessed per investigator. Ongoing response at last tumor assessment before censoring. Bar indicates progression-free survival. (D) Kaplan-Meier plot of progression-free survival. Progression-free survival was defined as the time from randomization to date of first documented tumor progression, death or last evaluable tumor assessment (censoring date). All randomized patients (nivolumab, n = 292; docetaxel, n = 290). Symbols represent censored observations. CI = confidence interval; ECOG PS = Eastern Cooperative Oncology Group performance status; EGFR = epidermal growth factor receptor; HR = hazard ratio; OS = overall survival; PFS = progression-free survival; RECIST = Response Evaluation Criteria In Solid Tumors.

Fig. 1. Efficacy of nivolumab versus docetaxel in patients with advanced non-squamous NSCLC

Data are based on a March 18, 2015 database lock. (A) Kaplan-Meier plot of overall survival. All randomized patients (nivolumab, n = 292; docetaxel, n = 290). Symbols represent censored observations. (B) Treatment effect on overall survival in pre-defined subsets. All randomized patients (nivolumab, n = 292; docetaxel, n = 290). HR was not computed for other subsets with less than 10 patients per treatment group. (C) Characteristics of response and progression as assessed per investigator. Ongoing response at last tumor assessment before censoring. Bar indicates progression-free survival. (D) Kaplan-Meier plot of progression-free survival. Progression-free survival was defined as the time from randomization to date of first documented tumor progression, death or last evaluable tumor assessment (censoring date). All randomized patients (nivolumab, n = 292; docetaxel, n = 290). Symbols represent censored observations. CI = confidence interval; ECOG PS = Eastern Cooperative Oncology Group performance status; EGFR = epidermal growth factor receptor; HR = hazard ratio; OS = overall survival; PFS = progression-free survival; RECIST = Response Evaluation Criteria In Solid Tumors.

Fig. 1. Efficacy of nivolumab versus docetaxel in patients with advanced non-squamous NSCLC

Data are based on a March 18, 2015 database lock. (A) Kaplan-Meier plot of overall survival. All randomized patients (nivolumab, n = 292; docetaxel, n = 290). Symbols represent censored observations. (B) Treatment effect on overall survival in pre-defined subsets. All randomized patients (nivolumab, n = 292; docetaxel, n = 290). HR was not computed for other subsets with less than 10 patients per treatment group. (C) Characteristics of response and progression as assessed per investigator. Ongoing response at last tumor assessment before censoring. Bar indicates progression-free survival. (D) Kaplan-Meier plot of progression-free survival. Progression-free survival was defined as the time from randomization to date of first documented tumor progression, death or last evaluable tumor assessment (censoring date). All randomized patients (nivolumab, n = 292; docetaxel, n = 290). Symbols represent censored observations. CI = confidence interval; ECOG PS = Eastern Cooperative Oncology Group performance status; EGFR = epidermal growth factor receptor; HR = hazard ratio; OS = overall survival; PFS = progression-free survival; RECIST = Response Evaluation Criteria In Solid Tumors.

Fig. 1. Efficacy of nivolumab versus docetaxel in patients with advanced non-squamous NSCLC

Data are based on a March 18, 2015 database lock. (A) Kaplan-Meier plot of overall survival. All randomized patients (nivolumab, n = 292; docetaxel, n = 290). Symbols represent censored observations. (B) Treatment effect on overall survival in pre-defined subsets. All randomized patients (nivolumab, n = 292; docetaxel, n = 290). HR was not computed for other subsets with less than 10 patients per treatment group. (C) Characteristics of response and progression as assessed per investigator. Ongoing response at last tumor assessment before censoring. Bar indicates progression-free survival. (D) Kaplan-Meier plot of progression-free survival. Progression-free survival was defined as the time from randomization to date of first documented tumor progression, death or last evaluable tumor assessment (censoring date). All randomized patients (nivolumab, n = 292; docetaxel, n = 290). Symbols represent censored observations. CI = confidence interval; ECOG PS = Eastern Cooperative Oncology Group performance status; EGFR = epidermal growth factor receptor; HR = hazard ratio; OS = overall survival; PFS = progression-free survival; RECIST = Response Evaluation Criteria In Solid Tumors.