New TROPiCS-02 Data Back Sacituzumab Govitecan for Older Patients With Breast Cancer

Regardless of age, a survival benefit was seen across several indicators among pretreated patients who have endocrine-resistant hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer, according to new TROPiCS-02 (NCT03901339) study data¹ on efficacy, safety, and quality of life presented at this year’s San Antonio Breast Cancer Symposium.

Efficacy outcomes of progression-free survival (PFS), the primary study outcome, and secondary outcomes of overall survival (OS), overall response rate (ORR), and clinical benefit rate (CBR) were seen with sacituzumab govitecan (SG) compared with physician’s choice of treatment (TPC; single-agent chemotherapy), among patients younger than 65 years, at least 65 years, younger than 75 years, and at least 75 years. PFS was evaluated over 2 years, and OS, 3 years.

3-D illustration of breast cancer | Image credit: SciePro - stock.adobe.com

HR+/HER2– breast cancer is the most common form of breast cancer.²

To be included in TROPiCS-02, patients had to have a history of at least 1 endocrine therapy, taxane, and CDK4/6 inhibitor in any setting; 2 to 4 prior lines of chemotherapy for metastasis; and measurable disease by RECIST v1.1. Patients were randomized 1:1 to 10-mg/kg SG every 21 days on days 1 and 8 (n = 272) or TPC (capecitabine, vinorelbine, gemcitabine, eribulin), which was specified prior to randomization. Patients were then stratified by presence or not of visceral metastases, if they had received endocrine therapy in the metastatic setting for at least 6 months, and 2 or fewer or 3 or more prior lines of chemotherapy.

The final OS analysis, published in The Lancet in October, showed a median (IQR) OS of 14.4 (95% CI, 13.0-15.7) months with SG vs 11.2 (95% CI, 10.1-12.7) months with physician’s choice of chemotherapy over a median follow-up of 12.5 (95% CI, 6.4-18.8) months, for a 21% (P = .020) reduced mortality risk.³ Previous research also shows SG improved PFS a median 5.5 months compared with 4 months from TPC, for a 34% (P = .0003) reduced mortality risk.⁴

“The most important risk factor for breast cancer is age,” the study authors wrote. “Advanced age is associated with a higher rate of comorbidities, and with worse efficacy and greater toxicity from chemotherapy.”

In this post hoc analysis, most participants were female, were White, and had an ECOG Performance Status of 1, meaning they had trouble with physically strenuous activity but were ambulatory.⁵ Prior CDK4/6 inhibitor use and the presence of 4 or more comorbidities also were reported by most patients in each treatment group.

Among the patients younger than 65 years, median PFS, by blinded independent central review, was 5.5 (95% CI, 4.1-6.9) months in the SG cohort (n = 199) vs 4.1 (95% CI, 3.0-4.4) months in the TPC cohort (n = 204), for a 31% (95% CI, 0.53-0.89) reduced risk of death with SG. Median OS was 14.1 (95% CI, 12.7-16.4) vs 11.5 (95% CI, 10.3-13.3) months, respectively, for a 19% (95% CI, 0.64-1.02) reduced risk of death. The ORRs were 21 (95% CI, 16-27) and 14 (95% CI, 59-19) months and median durations of response (DOR) were 8.3 (95% CI, 6.5-9.7) and 5.6 (95% CI, 3.8-7.9) months.

Among the patients 65 years and older, median PFS was 6.7 (95% CI, 4.2-9.0) months with SG (n = 73) and 3.5 (95% CI, 1.5-5.6) months with TPC (n = 67), for a 41% (95% CI, 0.38-0.93) reduced risk of death with SG. Corresponding OS was 14.9 (95% CI, 12.0-17.5) and 10.1 (95% CI, 7.6-14.2) months, for a 20% (95% CI, 0.54-1.19) reduced risk of death. ORRs were 21 (95% CI, 12-32) and 15 (95% CI, 7-26) months, and median DOR, 6.9 (95% CI, 5.8–not estimable [NE]) and 4.3 (95% CI, 2.3-NE) months.

Among the patients younger than 75 years, median PFS was 5.5 (95% CI, 4.1-6.9) months with SG (n = 256) and 4.0 (95% CI, 3.1-4.4) with TPC (n = 263), for a 30% (95% CI, 0.56-0.87) reduced risk of death. Median OS was 14.6 (95% CI, 13.0-16.0) and 11.2 (95% CI, 10.1-12.9) months, for an 18% (95% CI, 0.67-1.01) reduced risk of death. ORRs were 21 (95% CI, 16-27) and 14 (95% CI, 10-18) months, and median DOR, 7.4 (95% CI, 6.5-8.9) and 5.6 (95% CI, 4.1-7.9) months.

Among the patients 75 years and older, median PFS was 9.0 (95% CI, 3.8-NE) months with SG (n = 16) and 5.5 (95% CI, 0.3-NE) months with TPC (n = 8), for a 70% (95% CI, 0.08-1.12) reduced risk of death with SG. Median OS was 12.3 (95% CI, 6.4-NE) and 11.6 (95% CI, 5.6-NE) months, for a 44% (95% CI, 0.20-1.56) reduced risk of death. ORRs were 19 (95% CI, 4-46) and 25 (95% CI, 3-65) months, and median DOR, not estimable and 2.5 (95% CI, 2.3-NE) months.

Safety data for all groups were as follows:

• 95% to 100% reported any-grade treatment-emergent adverse events (TEAEs)
• 60% to 81% reported grade 3/4 TEAEs, with patients 75 years and older receiving SG having the highest rate
• 28% to 50% reported TEAEs leading to dose reduction, with patients 75 years and older receiving SG again having the highest rate
• 3% to 17% reported TEAEs leading to treatment discontinuation, with patients 65 years and older receiving SG having the highest rate

The authors noted that the small cohort sizes of the group of patients 75 years and older may have limited their interpretation.

Additional findings show participants younger than 65 years had improved SG efficacy at a lower relative dose intensity (RDI) vs a higher RDI and significantly longer time to deterioration for fatigue with SG compared with TPC.

“Consistent with prior results in the intent-to-treat population, efficacy benefit was observed with SG vs TPC regardless of age subgroup, with manageable safety,” the TROPiCS-02 authors concluded. “SG demonstrated a favorable benefit/risk profile in older patients, supporting the use of SG vs TPC in this patient population, which is known to experience greater toxicity and lower efficacy with chemotherapy treatment.”

The FDA approved SG in February for use among patients with pretreated HR+/HER2– metastatic breast cancer.⁶

References

1. Bardia A, Schmid P, Tolaney SM, et al. Clinical outcomes by age subgroups in the phase 3 TROPiCS-02 study of sacituzumab govitecan vs treatment of physician’s choice in HR+/HER2– metastatic breast cancer. Poster presented at: San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Poster PO5-21-09.
2. Female breast cancer subtypes. American Cancer Society. Accessed December 8, 2023. https://seer.cancer.gov/statfacts/html/breast-subtypes.html
3. Rugo HS, Bardia A, Marmé F, et al. Overall survival with sacituzumab govitecan in hormone receptor–positive and human epidermal growth factor receptor 2–negative metastatic breast cancer (TROPiCS-02): a randomized, open-label, multicentre phase 3 trial. Lancet. 2023;402(10411):1423-1433. doi:10.1016/S0140-6736(23)01245-X
4. Rugo HS, Bardia A, Marmé F, et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2022;40(29):3365-3376. doi:10.1200/JCO.22.01002
5. ECOG Performance Status Scale. ECOG-ACRIN Cancer Research Group. Accessed December 8, 2023. https://tinyurl.com/5ydfekc4
6. McNulty R. FDA approves sacituzumab govitecan for pre-treated HR+/HER2– metastatic breast cancer. The American Journal of Managed Care. February 3, 2023. Accessed December 8, 2023. https://www.ajmc.com/view/fda-approves-sacituzumab-govitecan-for-pre-treated-hr-her2--metastatic-breast-cancer