Sacituzumab Govitecan Leads to Mixed Results in Phase 3 NSCLC Trial

The phase 3 EVOKE-01 study (NCT05089734) investigating the antibody-drug conjugate (ADC) sacituzumab govitecan (Trodelvy) for the treatment of metastatic non–small cell lung cancer (NSCLC) that progressed after prior treatment failed to meet statistical significance for the primary end point of overall survival (OS). However, the reduction in risk of death and OS were numerically higher among patients treated with sacituzumab govitecan vs docetaxel.^1,2

The median OS in the sacituzumab govitecan arm was 11.1 months vs 9.8 months in the docetaxel arm (HR, 0.84; 95% CI, 0.68-1.04; 1-sided P =.0534), demonstrating a 16% reduction in risk of death. Further, sacituzumab govitecan appeared to be better tolerated that docetaxel, and no new safety signals were identified.

“There is an unmet medical need for safe and effective treatment options that prolong survival in patients with metastatic NSCLC who progressed on/after platinum-based chemotherapy and combination/sequential anti–PD-(L)1–containing regimen. EVOKE-01 is one of the first ADC studies in this setting. Although the study did not meet protocol-specified statistical significance for the primary end point of OS, [sacituzumab govitecan] treatment resulted in a 16% reduction in risk of death vs docetaxel in the [intent-to-treat] population and was associated with a numerically higher OS rate at all prespecified landmark time points,” authors wrote in findings published in the Journal of Clinical Oncology.²

Regarding progression-free survival (PFS), the median PFS was 4.1 months with sacituzumab govitecan vs 3.9 months with docetaxel (HR, 0.92; 95% CI, 0.77-1.11). The median PFS was similar among patients with squamous and nonsquamous histologies at 3.8 months (95% CI, 2.8-5.4) and 4.1 months (95% CI, 2.9-5.3), respectively.

Treatment-emergent adverse events (TEAEs) were reported in 99.7% and 97.9% of the sacituzumab govitecan and docetaxel arms, respectively. There was a higher proportion of diarrhea, alopecia, nausea, anemia, constipation, vomiting, pruritus, and abdominal pain reported in the sacituzumab govitecan arm, while more incidences of neutropenia, stomatitis, leukopenia, peripheral edema, dysgeusia, and peripheral neuropathy were reported in the docetaxel arm. Seven deaths were considered treatment-related, including 4 patients treated with sacituzumab govitecan and 3 patients treated with docetaxel.

“Patients with metastatic NSCLC still need novel treatment options, and these data support further investigation of [sacituzumab govitecan] in this patient population,” study authors concluded.

REFERENCES:

1. Sacituzumab govitecan does not demonstrate a statistically significant OS improvement in patients with previously treated advanced or metastatic NSCLC. News release. ESMO. July 30, 2024. Accessed August 2, 2024. https://tinyurl.com/7cykc6jm

2. Paz-Ares L, Juan-Vidal O, Mountzios G, et al. Sacituzumab govitecan versus docetaxel for previously treated advanced or metastatic non–small cell lung cancer: the randomized, open-label phase III EVOKE-01 study. J Clin Oncol. Published online May 31, 2024. doi:10.1200/JCO.24.00733