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ASCO 2022 | TROPiCS-02: sacituzumab govetican improves PFS versus physicians choice for HR+/HER2- mBC
Hope Rugo, MD, FASCO, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, provides an overview of the multicentered randomized Phase III TROPiCS-02 (NCT03901339) trial investigating the antibody-drug conjugate (ADC), sacituzumab govitecan, versus treatment of physicians choice in patients with HR-positive, HER2-negative metastatic breast cancer (mBC) who were heavily pretreated and failed at least two lines of prior therapy. Treatment of physicians choice included capecitabine, gemcitabine or vinorelbine. 543 patients were enrolled onto the trial, almost 100% of which had visceral metastases. The primary endpoint of progression-free survival (PFS) was met and a 34% improvement in PFS was demonstrated in patients treated with sacituzumab govitecan compared to treatment of physicians choice. At 12 months, 21% of patients were free of progression or death with sacituzumab govitecan versus 7% of patients on treatment of physicians choice. A key secondary endpoint is overall-survival (OS), which was not met at the first-interim analysis. Safety was comparable to previous reports on sacituzumab govitecan and quality of life was better with sacituzumab govitecan versus physicians treatment of choice. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.
Transcript (edited for clarity)
Well, certainly at ASCO 2022 antibody-drug conjugates stole the scene in the treatment of metastatic breast cancer. TROPiCS-02 was at phase three, multicenter randomized trial, that treated patients with either the antibody-drug conjugates sacituzumab govitecan or treatment of physician’s choice. The patients had hormone receptor positive HER2 negative metastatic breast cancer. But unique to this study, the patients were quite heavily pretreated...
Well, certainly at ASCO 2022 antibody-drug conjugates stole the scene in the treatment of metastatic breast cancer. TROPiCS-02 was at phase three, multicenter randomized trial, that treated patients with either the antibody-drug conjugates sacituzumab govitecan or treatment of physician’s choice. The patients had hormone receptor positive HER2 negative metastatic breast cancer. But unique to this study, the patients were quite heavily pretreated. So they had to have received at least one endocrine therapy, all patients had to have received a CDK4/6 inhibitors and a taxane in any setting. And then they also had to receive two to four lines of chemotherapy. And the median number of lines of chemotherapy, the patients received was three with more than 50% of patients receiving three or more lines of chemotherapy. In addition, these patients had visceral metastases, almost a hundred percent of the patients had visceral metastases and their median time from diagnosis of metastatic disease until entry in the trial was four years.
So this was a unique patient group, very heavily pretreated with limited chemotherapy options. And more than about 80% of the patients had, had prior capecitabine. The chemotherapy options in the treatment of physician’s choice arm included capecitabine, gemcitabine, vinorelbine, and eribulin. So the primary endpoint of this trial was progression free survival by blinded independent central review. We did not centrally confirm hormone receptor status, but we met the primary endpoint with a statistically significant improvement in progression-free survival.
The statistical plan had targeted a hazard ratio 0.7. The study ended up with a hazard ratio 0.66 corresponding to a 34% relative improvement in progression-free survival. The absolute numbers for the median were four months for chemotherapy in 5.5 months for sacituzumab govitecan.
Now, one of the things that we’ve seen in these later line studies where patients who are treated have really large burden of disease and a lot of resistance to standard therapies is that there’s an immediate fall off where the experimental group and the standard group have a lot of progression events in the first two months. So because of that, that can affect our assessment of the absolute differences in median PFS. So we looked at landmark analyses and at six, nine and 12 months, there was this a really clinically relevant improvement in the percent of patients who are free of progression or death compared with sacituzumab compared to chemotherapy. Most importantly at one year, 21% of patients were free of progression and death with sacituzumab and only 7% with chemotherapy. So really a threefold increase. Of course, overall survival was a secondary endpoint. This was the first interim analysis and although numerically was a little bit longer, it wasn’t significantly different.
There are two more survival analysis planned. We looked at safety and quality of life. Safety was comparable with previous studies with sacituzumab and global quality of life using a standard guideline. The EORTC quality of life guideline was improved with sacituzumab as was fatigue, and the pain scores were equivalent and more data will be presented on that in the future. So overall we also looked at response rate and duration of response, all of those endpoints were improved with sacituzumab compared to chemo. So sacituzumab govitecan I think represents a new and important treatment option for patients who have heavily pretreated hormone receptor, positive metastatic breast cancer.
Hope Rugo: (04:00)
One of the questions that came up is how do we put this data into context with a really truly remarkable data from DESTINY-Breast04, presented at the plenary session in patients who have had too low metastatic breast cancer of which the majority had hormone receptor, positive disease, 65% of patients with hormone receptor positive disease are felt to have had too low. It is certainly an area and a definition that’s under transition, which we’re trying to understand, but patients also need sequential therapy and we need to have different treatment options for patients who either aren’t eligible for or can’t tolerate T-DXd trastuzumab deruxtecan. So I think that what we’ve seen here at ASCO 22 is that antibody-drug conjugates offer a really remarkable and new way to deliver chemotherapy in a more effective and reasonably safe way they still are chemotherapy. There were three deaths on DESTINY-Breast04 from pneumonitis. But I think that as we learn more, we can really control those toxicities as wel