Updated findings from the phase 2 TROPiCS-03 trial reveal that sacituzumab govitecan-hziy (Trodelvy) exhibits notable antitumor activity and a manageable safety profile in patients with extensive-stage small cell lung cancer (ES-SCLC) who have progressed following platinum-based chemotherapy and PD-L1-directed therapy. The data, presented at the 2024 IASLC World Conference on Lung Cancer, suggest a potential new treatment option for this aggressive disease.
The open-label, multicohort TROPiCS-03 trial evaluated sacituzumab govitecan in patients with metastatic or locally advanced solid tumors. The ES-SCLC cohort included 43 patients who received intravenous sacituzumab govitecan at 10 mg/kg on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response rate (ORR).
Efficacy Outcomes
At a data cutoff of March 8, 2024, and a median follow-up of 12.3 months, the investigator-assessed ORR was 41.9% (95% CI, 27.0%-57.9%), with all responses being confirmed partial responses (PRs). The disease control rate (DCR) was 83.7% (95% CI, 69.3%-93.2%), and the clinical benefit rate (CBR) was 48.8% (95% CI, 33.3%-64.5%). The median duration of response (DOR) was 4.7 months (95% CI, 3.5-6.7), and the median time to response was 1.4 months (range, 1.2-4.2).
The median progression-free survival (PFS) was 4.40 months (95% CI, 3.81-6.11), with an 8-month PFS rate of 36.6%. The median overall survival (OS) was 13.60 months (95% CI, 6.57-14.78), and the 12-month OS rate was 50.3%.
"Almost all responses were brisk, with the first scan done at 6 weeks; some of these responses are durable," said lead study author Dr. Afshin Dowlati, Professor at Case Western Reserve University School of Medicine.
Outcomes in Platinum-Resistant and -Sensitive Subgroups
In patients with platinum-resistant disease (n = 20), the ORR was 35.0% (95% CI, 15.4%-59.2%), with a DCR of 70.0% (95% CI, 45.7%-88.1%). The median DOR was 6.3 months (95% CI, 1.5-6.9), the median PFS was 3.8 months (95% CI, 1.4-7.6), and the median OS was 6.6 months (95% CI, 4.7-17.7).
For those with platinum-sensitive disease (n = 23), the ORR was 47.8% (95% CI, 26.8%-69.4%), and the DCR was 95.7% (95% CI, 78.1%-99.9%). The median DOR was 4.4 months (95% CI, 3.0-NR), the median PFS was 5.0 months (95% CI, 4.1-7.4), and the median OS was 14.7 months (95% CI, 7.7-NR).
Safety Profile
The safety profile of sacituzumab govitecan in this study was consistent with previous findings. All patients experienced treatment-emergent adverse events (TEAEs), with 74.4% experiencing grade 3 or higher TEAEs. The most common TEAEs included diarrhea (67%), fatigue (58%), and neutropenia (44%). Serious TEAEs occurred in 51.2% of patients. Notably, no patients discontinued treatment due to adverse events.
Implications and Future Directions
These findings suggest that sacituzumab govitecan is a promising second-line treatment option for patients with ES-SCLC, including those with both platinum-resistant and platinum-sensitive disease. The manageable safety profile and encouraging efficacy data have led to the initiation of a randomized phase 3 study to further investigate its role in this setting.
"The safety profile was very similar to prior sacituzumab govitecan studies... These encouraging data are leading to a randomized phase 3 study in relapsed ES-SCLC," Dr. Dowlati concluded.
