Add-on docetaxel confers survival advantage in ICI-naïve NSCLC, with caveat

In the treatment of patients with ICI-naïve nonsmall cell lung cancer (NSCLC), adding the cytotoxic chemotherapy docetaxel to the immune-checkpoint inhibitor (ICI) nivolumab leads to a significantly longer survival, although at the expense of slightly elevated toxicity, according to the results of a phase II/III trial.

The trial included patients with histologically or cytologically proven NSCLC, stage IIIB/ IIIC/IV or postoperative recurrence, who received one or two previous chemotherapy regimens, excluding epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI). They were randomized to receive nivolumab either as a monotherapy or in combination with docetaxel. Nivolumab was given at 240 mg per body every 2 weeks, while docetaxel was administered at 60 mg/m² every 4 weeks.

The full analysis set included 128 patients (median age 69 years, 69.5 percent male), with 64 in each arm. EGFR mutation was detected in 14 (21.9 percent) and 13 (20.3 percent) patients in the monotherapy and combination arms, respectively. None of the patients had ALK translocation.

In the phase II trial, the 6-month progression-free survival (PFS) rate with the combination was 64.4 percent (80 percent confidence interval [CI], 53.4–73.5). There were no cases of grade ≥3 pneumonitis recorded at the data cutoff.

In the phase III trial, the primary endpoint of overall survival (OS) was significantly better with the combination vs monotherapy (23.1 months, 95 percent CI, 16.7–NR vs 14.7 months, 95 percent CI, 11.4–18.7; hazard ratio [HR], 0.63, 90 percent CI, 0.42–0.95; p=0.0310). The same was true for PFS (6.7 months, 95 percent CI, 3.8–9.4 vs 3.1 months, 95 percent CI, 2.0–3.9; HR, 0.58, 95 percent CI, 0.39–0.88; p=0.0095).

The objective response rates were 14.0 percent in the monotherapy arm and 41.8 percent (95 percent CI, 28.7–55.9) in the combination arm. Hematotoxicity and gastrointestinal adverse events were more common in the combination than in the monotherapy arm. There were two treatment-related deaths documented, one due to pneumonitis in the monotherapy arm and another due to myocarditis in the combination arm.