Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer

Abstract

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Parallel Genomic Alterations of Antigen and Payload Targets Mediate Polyclonal Acquired Clinical Resistance to Sacituzumab Govitecan in Triple-Negative Breast Cancer

“…In the pivotal EMILIA trial, which led to approval of the HER2-directed ADC trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer, the survival benefit with T-DM1 compared to control arm was greater in patients whose tumors had high HER2 mRNA levels (Hazard Ratio = 0.53; median OS, 34.1 vs. 26.5 months), compared to lower HER2 mRNA levels (Hazard Ratio, 0.80; median OS, 24.8 vs. 23.7 months) (17). Similarly, in the confirmatory phase 3 clinical trial with SG (ASCENT), patients with mTNBC who had high or medium TROP2 expression had higher objective response rates (44% and 39% respectively), as compared to low TROP2 expression (22%) (8,18). Furthermore, out of seven patients who had tumors with complete Cancer Research.…”

Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer

“…It should be noted that in the phase 3 ASCENT trial, the majority of patients (80%) had high/medium tumor TROP2 expression and the small number of patients with low TROP2 expression limits definitive conclusions on benefit of sacituzumab govetican on this group. 41 Currently, it remains unclear whether the extent of TROP2 expression is related to clinical benefit and would F7AK3 be appropriate in patients with low TROP2 expression such as ER + tumors. More in vivo studies with higher doses and subtypes of breast cancers with differential TROP2 expression levels would provide valuable information on the antitumoral effects of F7AK3.…”

Sacituzumab govitecan and trastuzumab deruxtecan: two new antibody–drug conjugates in the breast cancer treatment landscape

“…Treatment discontinuations due to AE were infrequent both for SG and TPC (4.7% and 5.4%, respectively), while dose reductions and interruptions occurred in 26% versus 22% of patients and in 61% versus 33% in the SG versus TPC arms, respectively. 30,32 The efficacy of SG was not impaired by dose reductions. A dose reduction of 25% and administration of G-CSF is recommended in patients treated with SG experiencing grade 4 neutropenia !7 days, grade 3 febrile neutropenia or a delay of the next scheduled dose because of grade 3-4 neutropenia by 2 or 3 weeks before recovery to grade 1.…”

“…The magnitude of benefit seems lower in patients with low Trop-2 H-scores (20.3% of the biomarker-evaluable population), but the low numbers warrant caution in the interpretation. 29,30 A subgroup analysis of patients with baseline brain metastases (n ¼ 61) showed numerically better PFS in patients randomized to SG versus TPC but no improvement in OS, but the small sample size limits interpretation. 31 Treatment-related adverse events (TRAEs) observed in ASCENT were reported for all patients (including those with brain metastases at diagnosis) who received !1 dose of study treatment (n ¼ 482) and are summarized in Table 1.…”