The anti-Trop-2 antibody-drug conjugate sacituzumab govitecan has shown an overall survival benefit in heavily pre-treated patients with hormone receptor (HR)-positive/HER2-negative metastatic breast cancer.
Findings from the phase 3 TROPiCS-02 trial, presented at ESMO 2022 meeting in Paris, showed that treatment with sacituzumab govitecan resulted in significant and “clinically meaningful” improvement in OS, as well as significant improvement in overall response rate (ORR) and quality of life compared with treatment of physician’s choice.
The TROPiCS-02 study involved 543 patients who were randomised to receive sacituzumab govitecan (272) or treatment of physician’s choice (271). The patients had a median of three prior chemotherapies for metastatic breast cancer and 95% had visceral metastases.
The trial met its primary endpoint of statistically significant progression-free survival (PFS) benefit with sacituzumab govitecan (median 5.5 vs 4.0 months vs usual choice) and a 12-month PFS rate of 21% versus 7%, with results previously reported at ASCO.
Secondary outcomes, newly reported at ESMO meeting, showed a statistically significant improvement in OS after a median follow-up of 12.6 months, (median 14.4 months for sacituzumab govitecan versus 11.2 months with treating physicians choice; HR 0.79 [95% confidence interval (CI) 0.65–0.96]; p=0.02).
The ORR was 57% vs 38% and the 12 month OS was 61% vs 47% for the two groups, respectively.
Tolerability, as measured by time-to-deterioration (TTD) for global health score and quality of life, was significantly better for sacituzumab govitecan compared to physician’s choice of treatment (4.3 vs 3.0 months, HR 0.75), as was the outcome for fatigue (HR 0.73).
Study investigator Dr Hope Rugo, a medical oncologist at University of California San Francisco (UCSF), said the results showed the drug conjugate, which is currently approved for treatment of patients with metastatic triple-negative breast cancer, may also be useful in women with hormone receptor–positive tumours.
The study authors noted that endocrine therapy combined with CDK4/6 inhibitor has extended overall survival for metastatic HR-positive, HER2-negative breast cancer to over five years in the first-line setting. Also, combinations with PI3K or mTOR inhibitors offered benefit in subsequent treatment lines, but endocrine resistance eventually develops. Sequential single-agent chemotherapy is the next treatment option but is associated with declining response rates and disease control and increased toxicity, they said.
“The statistically significant and clinically meaningful benefit of sacituzumab govitecan over treatment by physician’s choice from the TROPiCS-02 study supports the use of sacituzumab as a novel therapy for patients with pretreated endocrine-resistant hormone receptor–positive, HER2-negative metastatic breast cancer,” said Dr Rugo.
The study investigators added that it was difficult to make comparisons with the antibody drug conjugate trastuzumab deruxtecan in patients with HR-positive, HER2-low metastatic breast cancer because the there were important differences in the patient populations enrolled in key trials. For the latter, the DESTINY-Breast04 only included patients with HER2-low less heavily pretreated disease with median number of prior chemotherapies in the metastatic setting as one, along with other differences, they said.
Commenting on the results of the TROPiCS-02 trial, Dr Giampaolo Bianchini, from Ospedale San Raffaele, Milan, Italy, said the results offered promise for patients when the efficacy of chemotherapy decreases over subsequent treatment lines.
And although the amount of benefit demonstrated was not “transformative” compared to the effects seen in triple-negative breast cancer, the results from the TROPiCS-02 trial showed a clinically meaningful incremental impact for patients with very limited treatment options, said Dr Bianchini.
The study was sponsored by Gilead Sciences Inc.