Sacituzumab Govitecan Misses OS End Point in Metastatic NSCLC

The phase 3 EVOKE-01 study found that OS improved numerically, but not statistically significantly, in sacituzumab govitecan vs docetaxel with a similar safety profile.

Sacituzumab govitecan (Trodelvy), a TROP2-directed antibody-drug conjugate (ADC), did not meet statistical significance for overall survival (OS) compared with docetaxel in patients with metastatic non-small cell lung cancer (mNSCLC), missing the primary end point of an open-label phase 3 study (NCT05089734). The results were published in the Journal of Clinical Oncology.¹

Investigators found a numerical increase in OS consistent across squamous and nonsquamous histologies for sacituzumab govitecan over docetaxel of 11.1 months vs. 9.8 months (HR, 0.84; 95% CI, 0.68-1.04; one-sided P = .0534). Furthermore, a median 3.5-month OS increase was observed for the experimental treatment over comparator across histologies in mNSCLC that were nonresponsive to PD-L1–containing regimens (HR, 0.75, 95% CI, 0.58-0.97).

“[The] failure of [sacituzumab govitecan] to improve ORR and PFS and to extend in a clinically meaningful way OS in comparison with docetaxel makes the EVOKE-01 results disappointing,” said Maurice Pérol, MD, head of department at the Cancer Research of Lyon in France and Journal of Clinical Oncology editorial board member, said in an editorial on the study findings.² “The two keys to the future of current anti-TROP2 drugs in first-line treatment of advanced NSCLC are whether they will be better partners for immunotherapy than conventional chemotherapy in their ability to generate a real synergy via an immunogenic cell death and the control or prophylaxis of their toxicities, which can overlap those of anti–PD(L)-1 and have a significant impact on patients' quality of life.”

Patients with stage IV NSCLC were selected for the study (n = 603) between November 17, 2021 and May 30, 2023 and were randomized 1:1 to receive either intravenous (IV) sacituzumab govitecan at 10 mg/kg on days 1 and 8 of a 3-week cycle (n = 299) or IV docetaxel on the first day of each 3-week cycle (n = 304).

Treatment continued until discontinuation criteria were met, which included disease progression and unacceptable toxicity.

The study’s primary end point was OS. Progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), disease control rate (DCR), and safety were all secondary efficacy end points.

For the investigational and comparator arms, 296 (99.0%) and 288 (94.7%) patients received treatment. Consent was withdrawn for 12 of the 19 patients randomly assigned but not treated.

Median follow-up was 12.7 months (range, 6.0-24.0) with a median duration of exposure of 3.45 months (range, 0.03-18.69) in the experimental group vs 2.33 months (range, 0.03-19.75) in the comparator arm. In the sacituzumab govitecan and docetaxel groups, 122 (40.8%) and 101 (33.2%) of patients remained don study as of data cutoff date.

The 12-month OS rate between the sacituzumab govitecan and docetaxel groups was 46.59% (95% CI, 40.45%-52.50%) and 36.72% (95% CI, 30.88%-42.57%), respectively.

Median PFS was 4.1 months (95% CI, 3.0-4.4) vs 3.9 months (95% CI, 3.1-4.2) in the investigational and comparator arms, respectively. Furthermore, the 6-month PFS rates were 33.71% (95% CI, 28.21%-39.28%) and 31.39% (95% CI, 25.75%-37.17%), respectively.

“Although EVOKE-01 did not meet statistical significance for the primary end point, [sacituzumab govitecan] is an active therapeutic agent in metastatic NSCLC that conferred modest numerical OS benefit over docetaxel in the ITT population. A numerical OS benefit was also observed in the subgroup of patients who were nonresponsive to last anti–PD-(L)1–containing regimen. Patients with metastatic NSCLC still need novel treatment options, and these data support further investigation of [sacituzumab govitecan] in this patient population,” lead study author Luis Paz-Ares, MD, PhD, chairman of the Medical Oncology Department at the Hospital Doce de Octubre, in Madrid, Spain, and coinvestigators wrote in the study.¹

References

1. Paz-Ares LG, Juan-Vidal O, Mountzios GS, 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 ahead of print. May 31, 2024. doi:10.1200/JCO.24.00733
2. Pérol M. TROP2-directed antibody-drug conjugates in advanced non–small cell lung cancer: a fading hope? J Clin Oncol. Published online ahead of printJuly 10, 2024. doi:10.1200/JCO.24.01043