As reported in the Journal of Clinical Oncology by Luis G. Paz-Ares, MD, PhD, and colleagues, the phase III EVOKE-01 trial has shown a numeric but not statistically significant improvement in overall survival with sacituzumab govitecan-hziy vs docetaxel in patients with metastatic non–small cell lung cancer (NSCLC) who had disease progression on or after platinum-based chemotherapy, anti–PD-1/PD-L1 therapy, and targeted treatment for actionable genomic alterations.
Luis G. Paz-Ares, MD, PhD
Study Details
In the open-label trial, 603 patients from sites in 20 countries were randomly assigned between November 2021 and May 2023 to receive sacituzumab govitecan at 10 mg/kg on days 1 and 8 (n = 299) or docetaxel at 75 mg/m2 on day 1 (n = 304) of 21-day cycles. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival, with a significance threshold of P ≤ .0223.
Overall Survival
Median follow-up was 12.7 months (range = 6.0–24.0 months). There was a numeric improvement in overall survival with sacituzumab govitecan vs docetaxel (median = 11.1 vs 9.8 months; hazard ratio [HR] = 0.84, 95% confidence interval [CI] = 0.68–1.04, P = .0534), with the significance threshold not being met. Overall survival at 12 months was 46.6% vs 36.7%. The numeric benefit of sacituzumab govitecan was observed across most predefined subgroups, including patients with squamous (HR = 0.83, 95% CI = 0.56–1.22) and nonsquamous (HR = 0.87, 95% CI = 0.68–1.11) histologies. A benefit of sacituzumab govitecan vs docetaxel was observed among the 192 vs 191 patients without response to last anti–PD-1/PD-L1–containing regimen, with a median overall survival of 11.8 vs 8.3 months (HR = 0.75, 95% CI = 0.58–0.97) and 12-month rates of 47.7% vs 34.0%; this benefit was also observed across histologies.
Median progression-free survival was 4.1 months vs 3.9 months (HR = 0.92, 95% CI = 0.77–1.11), with 12-month rates of 33.7% vs 31.4%. Subsequent anticancer therapy was received by 37.8% of the sacituzumab govitecan group (most commonly, docetaxel) and 31.3% of the docetaxel group (most commonly, single-agent gemcitabine or vinorelbine).
Adverse Events
Grade ≥ 3 adverse events occurred in 66.6% of the sacituzumab govitecan group vs 75.7% of the docetaxel group. Treatment-related adverse events led to treatment discontinuation in 6.8% vs 14.2% of patients. Death considered related to treatment occurred in four patients (1.4%) in the sacituzumab govitecan group (due to febrile neutropenia, neutropenic colitis, sepsis, and septic shock) and three patients (1.0%) in the docetaxel group (due to unknown cause, pneumonia, and pneumonitis).
The investigators concluded, “Although statistical significance was not met, overall survival numerically improved with sacituzumab govitecan vs docetaxel, which was consistent across histologies. Clinically meaningful improvement in overall survival was noted in [patients with] metastatic NSCLC nonresponsive to last [anti–PD-1/PD-L1]–containing regimen. Sacituzumab govitecan was better tolerated than docetaxel and consistent with its known safety profile, with no new safety signals.”
Dr. Paz-Ares, of Hospital Universitario 12 de Octubre, Complutense University and Ciberonc, Madrid, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Gilead Sciences, Inc. For full disclosures of the study authors, visit ascopubs.org.
