article · Journal of Clinical Oncology
A randomised phase 3 clinical trial evaluated the combination of sacituzumab govitecan and pembrolizumab against standard chemotherapy plus pembrolizumab in 443 patients with previously untreated, PD-L1-positive advanced triple-negative breast cancer. Patients receiving sacituzumab govitecan and pembrolizumab achieved a median progression-free survival of 11.2 months compared to 7.8 months for those receiving chemotherapy and pembrolizumab. The sacituzumab govitecan combination also extended the median duration of response to 16.5 months compared with 9.2 months for the chemotherapy group. While severe adverse events occurred at similar frequencies across both treatment groups, the sacituzumab govitecan combination led to a substantially lower rate of treatment discontinuation due to adverse events. Overall, the results demonstrate a statistically significant and clinically meaningful delay in disease progression without introducing new safety concerns.
Advanced triple-negative breast cancer is an aggressive disease with limited first-line therapeutic options. While immunotherapy paired with chemotherapy has improved outcomes, durable disease control remains difficult to achieve. Demonstrating that an antibody-drug conjugate can replace conventional chemotherapy while extending progression-free survival and reducing treatment dropouts offers a meaningful step forward for clinical oncology and patient care.
This therapy is near-market, having successfully generated primary efficacy and safety data in a phase 3 clinical trial. The combination of sacituzumab govitecan and pembrolizumab is targeted for use by medical oncologists and cancer care centres. The positive trial outcomes provide the clinical evidence necessary to support regulatory submissions for a new standard-of-care first-line treatment for advanced triple-negative breast cancer.
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LBA109 Background: Although PD-1/PD-L1 inhibitors plus chemo have expanded treatment options for previously untreated PD-L1–positive advanced TNBC, there still remains a critical unmet need to improve outcomes. SG previously demonstrated significant clinical benefit in pretreated metastatic TNBC (mTNBC). We report results from the ASCENT-04/KEYNOTE-D19 study in patients with previously untreated, PD-L1–positive (CPS ≥ 10; 22C3 assay) locally advanced unresectable or mTNBC. Methods: Patients were randomized 1:1 to SG (10 mg/kg IV, day 1 & 8) + pembro (200 mg, day 1, max 35 cycles) in 21-day cycles or chemo (gemcitabine + carboplatin, paclitaxel, nab-paclitaxel) + pembro until disease progression or unacceptable toxicity. Randomization was stratified by curative treatment-free interval, geography, and prior exposure to anti–PD-(L)1 therapy in the curative setting. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR). Key secondary endpoints include overall survival (OS); objective response rate (ORR) and duration of response (DOR) by BICR; and safety. Results: 443 patients were randomized at a 1:1 ratio: 221 to SG + pembro and 222 to chemo + pembro. The median follow-up was 14 mo. SG + pembro showed a significant improvement in PFS by BICR compared with chemo + pembro (hazard ratio [HR], 0.65; 95% CI, 0.51-0.84; P = .0009; Table). Median DOR was 16.5 mo for SG + pembro vs 9.2 mo for chemo + pembro (Table). Although OS data were immature, a positive early trend in OS improvement was also noted. The most frequent (≥ 10% of patients) grade ≥ 3 treatment-emergent adverse events (TEAEs) with SG + pembro were neutropenia (43%) and diarrhea (10%); and with chemo + pembro were neutropenia (45%), anemia (16%), and thrombocytopenia (14%). Conclusions: SG + pembro led to a statistically significant and clinically meaningful improvement in PFS vs chemo + pembro with durable responses, no new safety concerns for SG or pembro, and a lower rate of treatment discontinuation due to TEAEs in patients with previously untreated, PD-L1–positive advanced TNBC. These data support the use of SG + pembro as a potential new standard of care treatment in this patient population. Clinical trial information: NCT05382286 . Efficacy, BICR, intent-to-treat SG + pembro(n = 221) Chemo + pembro(n = 222) Median PFS (95% CI), mo 11.2 (9.3-16.7) 7.8 (7.3-9.3) HR (95% CI); P -value (adjusted for randomization stratification factors) 0.65 (0.51-0.84); P = .0009 ORR (95% CI), % 59.7 (52.9-66.3) 53.2 (46.4-59.9) Median DOR (95% CI), mo 16.5 (12.7-19.5) 9.2 (7.6-11.3) Safety (TEAEs), all treated, n (%) n = 221 n = 220 Any grade; grade ≥ 3 220 (> 99); 158 (71) 219 (> 99); 154 (70) Led to dose reduction 78 (35) 96 (44) Led to any treatment discontinuation 26 (12) 68 (31)
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DOI: 10.1200/jco.2025.43.17_suppl.lba109
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