Hope S. Rugo, MD, spoke about results of the phase 3 TROPiCS-02 trial examining sacituzumab govitecan vs physicians’ choice chemotherapy for patients with hormone receptor–positive, HER2-negative advanced breast cancer presented at ASCO 2022.
At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® spoke with Hope S. Rugo, MD, FASCO, director of Breast Oncology and Clinical Trials Education and professor of medicine in the Division of Hematology and Oncology at the University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, about results of the phase 3 TROPiCS-02 trial (NCT03901339) which analyzed sacituzumab govitecan-hziy (Trodelvy) vs physicians choice chemotherapy for patients with hormone receptor–positive, HER2-negative advanced breast cancer.
TROPiCS-02 was a phase 3 randomized trial that evaluated the antibody-drug conjugate sacituzumab govitecan compared with physician’s choice of standard chemotherapy used in the late-line setting, [either] capecitabine, gemcitabine, vinorelbine, and eribulin. The patient population was unique. All patients had to have received a prior CDK4/6 inhibitor and a taxane in any line [of therapy], at least 1 endocrine therapy for metastatic disease, and 2 to 4 lines of chemotherapy for metastatic disease. [These were] very heavily pretreated patients, in fact the median number of prior chemotherapy lines was 3 with a range of 0 to 8 and about 95% of patients had visceral disease. This was a group of patients who were far out from diagnosis. The median time from diagnosis of metastatic disease to study entry was 4 years. Patients were randomized 1:1 and the primary end point was progression-free [PFS] survival by blinded independent central review. This was statistically significant with a median PFS of 4.0 months [95% CI, 3.1-4.4] for chemotherapy and 5.5 months [95% CI, 4.2-7.0] for sacituzumab govitecan. The hazard ratio is 0.66 [95% CI, 0.53-0.83] with a 34% relative benefit, and the P value of .0003.
One of the questions that’s come up is, why was the median [PFS improvement] only 1.5 months if the hazard ratio was so good. Really, that has to do with the shape of the Kaplan-Meier curve where a subset of [patients] have rapid progression. In the first 2 months, you saw that the curves stayed together and dropped and then they separated and stayed separated over time. We looked at landmark analyses at 6, 9, and 12 months. In each time period, the PFS was clinically and meaningfully longer in the patients receiving sacituzumab govitecan vs chemotherapy. Notably, at 12 months, 21% of patients were free of progression or death with sacituzumab govitecan vs only 7% with chemotherapy. It’s a threefold difference.
The trial also looked at safety and quality of life as well as response and duration of response [DOR]. In terms of the efficacy end points, the response was higher in patients who received sacituzumab govitecan, as was the clinical benefit rate and DOR. The safety was identical to what had been seen in other trials like the [phase 3] ASCENT trial [NCT02574455] with sacituzumab govitecan [in triple-negative breast cancer], with neutropenia and diarrhea being the most common grade 3 or greater toxicities. There was 1 death in the sacituzumab govitecan arm due to neutropenic colitis. Otherwise, the serious toxicities that resulted in death were unrelated to the study drug, like COVID-pneumonia during the COVID pandemic. Then we looked at the quality of life [QOL] using the EORTC-QOL scales. Patients had a better global QOL and also a better scale for fatigue with sacituzumab govitecan vs chemotherapy and the pain scores are about the same. Overall, that was a positive study that suggests that sacituzumab govitecan has a role in the treatment of heavily pretreated patients with hormone receptor–positive/HER2-negative metastatic disease.
Rugo HS, Bardia A, Marme F, et al. Primary results from TROPiCS-02: A randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (Pts) with hormone receptor–positive/HER2-negative (HR+/HER2-) advanced breast cancer. J Clin Oncol. 2022; 40(suppl 17):LBA1001. doi: 10.1200/JCO.2022.40.17_suppl.LBA1001