番茄社区app

Researchers compared real-world data with clinical trial results to see how well sacituzumab govitecan (SG, Trodelvy) performed in patients with metastatic triple-negative breast cancer (mTNBC).

Shipra Gandhi, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, and colleagues retrospectively analyzed data on 115 patients with mTNBC treated with SG from 2021 to 2023 at four academic centers in the United States.

Reporting in , the researchers observed an objective response rate (ORR) slightly lower than in the on which SG was approved for mTNBC (27% vs 35%). The real-world population had a median survival of 9.6 months compared with 12 months for ASCENT.

Despite the study's small sample size and retrospective design, it "contributes to the expanding body of knowledge on sacituzumab govitecan and provides reassurance to oncologists regarding its efficacy, alleviating concerns that it may not achieve the same level of effectiveness observed in the ASCENT trial," the study authors concluded.

Co-author Arya Mariam Roy, MD, a medical oncologist at Ohio State University in Columbus, discussed additional findings and implications in the following interview.

How did the patients in your study differ from those in ASCENT?

Roy: The patient population and demographics of our study differed slightly from those of the ASCENT trial. Our study included a total of 115 patients, whereas the ASCENT trial enrolled 468 patients. Compared with the ASCENT trial, our patients were slightly older, with a median age of 60 years at the time of SG initiation, and 34% of the patients were older than 65. In contrast, the ASCENT trial reported a median age of 54, with 20% of its population 65 and older.

Additionally, our study population was more diverse, consisting of 63.5% white patients and 27% Black patients, compared with the ASCENT trial, which included 80% white and 12% Black patients.

What did your study's findings indicate about dosing for sacituzumab govitecan?

Roy: The findings of this study suggest that most patients can be maintained on a high-intensity dose of SG. Notably, several patients received primary G-CSF [granulocyte colony-stimulating factor] prophylaxis, even though neither the ASCENT trial nor the FDA label recommends its routine use for neutropenia. This practice may have contributed to the preservation of dose intensity in this heavily pretreated population.

We evaluated the impact of relative dose intensity (RDI) on treatment efficacy. However, RDI was not observed to influence response outcomes, such as the ORR or clinical benefit rate.

Given that nearly half of the patients required dose reductions, initiating treatment at a lower dose than the ASCENT protocol may better preserve quality of life in heavily pretreated patients. Interestingly, our study population experienced a higher rate of dose reductions compared with the ASCENT trial (51.3% vs 22%), as well as a higher rate of treatment discontinuation (13% vs 5%).

What does your study suggest about the sequencing of trastuzumab deruxtecan after progression on SG?

Roy: Concerns exist regarding the sequencing of trastuzumab deruxtecan (T-DXd) following progression on SG due to their shared topoisomerase I payloads and the limited understanding of resistance mechanisms. In our study, none of the patients received T-DXd prior to SG. However, 26 patients (22.6%) were treated with T-DXd after experiencing progression or toxicity on SG therapy.

In the HER2-low subgroup who received T-DXd after SG, we observed a median progression-free survival (PFS) of 7 months, comparable to the median PFS of 8.5 months reported in DESTINY-Breast04 for the 40 patients with hormone receptor–negative breast cancer treated with T-DXd. Among our patients treated with T-DXd following SG, the ORR was 34.8%, and the clinical benefit rate was 65%.

Interestingly, clinical benefit with T-DXd was observed in approximately one-third of the patients who had previously derived clinical benefit from SG. In contrast, none of the patients who failed to achieve clinical benefit with SG went on to derive clinical benefit from T-DXd.

Although our study's small sample size and retrospective design are notable limitations, these findings provide some reassurance that T-DXd could be a viable treatment option after SG, particularly for patients who had a positive clinical response to SG. Prospective, large-scale studies are needed to further validate these observations.

How did your safety and tolerability results compare with ASCENT?

Roy: Neutropenia, anemia, vomiting, fatigue, and diarrhea were the most frequently reported clinically relevant grade 3 adverse events (AEs), occurring in 51% of the patients. Consequently, 51% of patients required dose reductions, and 13% discontinued treatment due to AEs.

Notably, clinical benefit was still observed in patients who received reduced doses of SG. This finding aligns with the ASCENT trial; however, the rate of dose reductions was notably higher in our real-world study.

In the ASCENT trial, grade 3 AEs were reported in 45% of patients, dose reductions occurred in 22%, and treatment discontinuation was observed in 5% of patients, compared with 13% in our study. The higher rates of grade 3 AEs and dose modifications in our cohort may reflect differences in patient characteristics or real-world practices.

Additionally, the UGT1A1 polymorphism, which impairs SN-38 detoxification, is known to be associated with increased rates of grade 3 AEs with SG. Importantly, none of the patients in our study were found to carry this mutation.

Is there anything else you want to make sure oncologists understand about your study?

Roy: The real-world effectiveness of sacituzumab govitecan (SG) aligns with the results observed in clinical trials, although with a higher incidence of toxicity and dose modifications. Given that RDI of SG did not impact response rates and dose reductions were frequently required, initiating treatment at a lower dose may be a reasonable consideration for heavily pretreated patients.

These findings highlight the potential of SG as an effective option for patients with primary refractory disease, addressing the needs of this challenging population.

Additionally, the sequential use of T-DXd following SG shows promise in the treatment of the HER2-low subset of mTNBC, offering further therapeutic opportunities. T-DXd can be considered for HER2-low TNBC patients who have shown clinical benefit with SG.

Read the study here and expert commentary about it here.