Table 2.

FDA risk–benefit assessment.

DimensionEvidence and uncertaintiesConclusions and reasons
Analysis of condition
  • Breast cancer is the most common cancer in women with more than 260,000 new cases and 40,000 deaths annually. Approximately 10%–15% of patients with breast cancer have TNBCs.

  • mTNBC has a poor prognosis with an estimated median OS of approximately 13 months.

mTNBC is a serious and life-threatening condition with an estimated median OS of approximately 13 months.
Current treatment options
  • The goals of treating mTNBC are palliative in nature with the aim of prolonging survival and reducing cancer-related symptoms. Available therapies for the treatment of patients with mTNBC who have had two prior lines of therapy include ixabepilone and eribulin; for patients with a BRCA1 or BRCA2 mutation, olaparib and talazoparib are available.

There is an unmet medical need to improve the outcomes of patients with mTNBC who have received two or more prior therapies, and patients may benefit from an agent with a more favorable response rate and DoR as compared with available therapy.
  • The efficacy of sacituzumab was evaluated in IMMU-132-01 trial.

  • In the 108 patients who comprised the efficacy population, the confirmed ORR was 33% (95% CI, 24.6–43.1) with an estimated median DoR of 7.7 months (95% CI, 4.9–10.8) per local investigator assessment.

Study IMMU-132-01 demonstrated an improvement over available therapy based on response rate, an endpoint reasonably likely to predict clinical benefit.
Risk and risk management
  • In the efficacy population, 33% of patients experienced SAEs compared with 41% of patients in the pooled safety population.

  • The serious risks of sacituzumab include diarrhea, neutropenia, nausea, vomiting, and infusion-related reactions. Patients who are homozygous for the UGT1A1*28 allele are at increased risk for neutropenia.

  • One death in the overall safety population was due to neutropenic typhlitis.

The safety profile of sacituzumab is acceptable when assessed in the context of the life-threatening nature of mTNBC that has progressed following two or more therapies. Significant and SARs, including neutropenia and diarrhea can be adequately managed with close monitoring, dose modifications, and supportive measures, and this risk should be conveyed in labeling. Patients with known reduced UGT1A1 activity should be monitored for severe neutropenia.