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This retrospective of multi-institutional real-world use of sacituzumab govitecan (SG) involved 115 patients with metastatic triple-negative breast cancer (mTNBC). The ASCENT clinical trial, which led to the approval of SG, studied the drug compared with physician-choice chemotherapy in pretreated mTNBC patients, and on final analysis has shown an overall response rate (ORR) of 31%, median progression-free survival (PFS) of 4.8 months, and median overall survival (OS) of 11.8 months.

The current study showed an ORR of 27.8%, median PFS of 4.8 months, and overall survival of 9.6 months. These findings suggest that SG is performing similarly in a non-clinical trial, real-world population.

In terms of therapy toxicity, higher rates of dose reductions were observed compared with the ASCENT trial (51.3% vs 22%). Discontinuation rates were also higher (13.2% vs <5%). Nearly half of the patients required granulocyte colony-stimulating factor (GCSF) support during SG therapy, with half receiving it as primary prophylaxis and half as secondary prophylaxis.

This observation aligns with clinical practice, even though the FDA label does not mandate primary prophylaxis. The authors suggest that GCSF use may have helped maintain dose intensity. However, they also note that higher dose intensity did not correlate with better responses, and clinical benefit was preserved despite dose reductions, consistent with the ASCENT trial's safety analysis. This finding supports the practice of dose reduction to manage toxicity and patients' quality of life.

Interestingly, the study reported a 34.8% clinical response rate in 26 patients treated with sequential trastuzumab deruxtecan following SG failure, with a median PFS of 7 months (95% CI 4.6–10.1).

The A3 trial -- Antibody Drug Conjugate (ADC) After ADC -- which addressed a similar question found a median PFS of 3.24 months for the second ADC, even with a change in antibody target, suggesting potential payload resistance in some patients. Larger prospective studies investigating resistance mechanisms are needed to optimize the sequencing of ADC therapies.

Nonetheless, in clinical practice, the observed benefit supports offering sequential ADC therapies in this setting while we await further data to guide optimal sequencing strategies.

The study is limited by its relatively small sample size and retrospective design; however, it offers valuable insights into the real-world use of SG and subsequent ADC therapies.

Rosana Gnanajothy, MD, is a breast medical oncologist and hematology oncology physician.

Read the study here and an interview about it here.