The first-in-class drug is directed at trophoblast cell surface antigen 2 (Trop-2), which is highly expressed in breast cancer. Research on the drug was presented at the European Society for Medical Oncology Virtual Congress 2020.
ASCENT randomly assigned more than 500 patients who had metastatic TNBC and who had experienced disease progression after a median of four lines of therapy to receive either SG or physician’s choice of chemotherapy. SG significantly improved median progression-free survival (5.6 vs 1.7 months; hazard ratio [HR], 0.41; P < .0001) and median overall survival (12.1 vs 6.7 months; HR, 0.48; P < .0001).
The response rate was 35% for SG vs 5% for chemotherapy (P < .0001).
The study was presented by Aditya Bardia, MD, MPH, a medical oncologist at Massachusetts General Hospital, Boston, Massachusetts.
He said that because the safety profile of SG is consistent with previous reports and the treatment discontinuation rate was low, the clinical benefit “confirms the use of sacituzumab govitecan” in metastatic TNBC. This was a reference to the fact that the drug previously received accelerated approval on the basis of early data.
Bardia added that ongoing studies are evaluating the use of SG in earlier lines of therapy, including neoadjuvant settings in combination with other targeted agents, as well as in hormone receptor–positive metastatic breast cancer. One such study is the phase 3 TROPiCS-02 study, which is actively accruing patients.
Invited discussant Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal, said the treatment algorithm for the management of TNBC will need to be updated in light of these results.
“In my opinion, we should now add sacituzumab govitecan as a new treatment option for patients treated with two or more lines of therapy,” she said.
She noted that the study design raised some questions over the way such trials should be conducted and the future sequencing of treatments.
Objections to study design and execution
Discussant Cardoso said the choice of progression-free survival as the primary endpoint for the trial was not ideal.
“In the metastatic setting, and particularly for triple-negative breast cancer, where the median survival is quite low and where each line of treatment, particularly after the second line, has a short duration, the primary endpoint should have been overall survival,” she commented.
“Luckily, we saw some results, but we could have missed it,” Cardoso said. She made “a plea to make sure that overall survival is at least the co–primary endpoint” in the future.
Cardoso also said it was not clear to her why the trial had to be stopped. “For the current patients, if there is no crossover, there is no benefit in stopping the trial,” she said.
She went on: “For future patients, it’s better to have the final results sufficiently powered.” She noted that the benefit seen in ASCENT was “moderate” and “so not a substantial breakthrough.” She added that it was “important not to stop trials too early.”
On the positive side, Cardoso said the median number of previous lines of therapy was “quite remarkable for this subtype, and it is important then for us to discuss sequencing,” particularly given that so many patients received checkpoint inhibitors before entering the trial.