Talazoparib Shows Real-World Clinical Benefit in Germline BRCA-Mutated, HER2-Negative, Advanced Breast Cancer

Clinical outcomes achieved with talazoparib (Talzenna) in a real-world population of patients with HER2-negative, locally advanced or metastatic breast cancer harboring germline BRCA (gBRCA) mutations proved to be consistent with those observed in the phase 3 EMBRACA trial (NCT01945775), according to data from a retrospective chart review study (NCT04987931).¹

The findings, which were presented during the 39th Annual Miami Breast Cancer Conference®, showed that at a median of 8.2 months of follow-up from the talazoparib initiation (range, 2.0-33.2) in all patients included in the real-world study (n = 84), the median progression-free survival (PFS) was 8.7 months (95% CI, 8.0-9.9), the overall tumor response rate (ORR) was 63% (95% CI, 52%-74%), and the median time to treatment failure (TTF) was 8.6 months (95% CI, 8.0-9.7). Similar outcomes were noted in the subsets of patients with hormone receptor–positive disease, and those with triple-negative breast cancer (TNBC).

Data from the EMBRACA trial showed that talazoparib resulted in a median PFS of 8.6 months (95% CI, 7.2.-9.3) vs 5.6 months (95% CI, 4.2-6.7) with physician’s choice of single-agent chemotherapy (HR, 0.54; 95% CI, 0.413-0.711; P < .001).2 Furthermore, talazoparib elicited an ORR of 62.6% vs 27.2% with chemotherapy (P < .001).

“While the [real-world] study sample size was limited, the potentially eligible patient population is considered to be rare, given the fact that gBRCA mutations are detected in less than 5% of unselected patients with metastatic breast cancer, and gBRCA mutation testing is not universally performed,” lead study author Reshma L. Mahtani, DO, chief, Breast Oncology, Miami Cancer Institute at Baptist Health South Florida, and colleagues, wrote in the poster.

Less than 5% of patients with metastatic breast cancer harbor gBRCA mutations.³ In October 2018, the FDA approved the PARP inhibitor talazoparib for the treatment of adult patients with deleterious or suspected deleterious gBRCA-mutated, HER2-negative, locally advanced or metastatic breast cancer based on findings from EMBRACA.⁴

Although past studies have analyzed patient characteristics, treatment patterns, and outcomes in patients who have received talazoparib in the real-world setting in France, Turkey, and Russia, no data exist regarding its use in clinical practice in the United States.

With this retrospective chart review study, investigators aimed to collect this information in adult patients with HER2-negative, locally advanced or metastatic breast cancer harboring gBRCA mutations who were treated with talazoparib in the United States.

To do this, oncologists from the Cardinal Health Oncology Provider Extended Network extracted information from medical records of patients residing in the United States. To be included in the analysis, patients must have received talazoparib monotherapy that was initiated on or after October 16, 2018, and they needed to be at least 18 years of age at the time of initiation. Moreover, there must have been at least 6 months of follow-up time after treatment with talazoparib was started, unless the patient died during that time.

If patients had participated in any breast cancer clinical trial after talazoparib initiation, if they received treatment with a PARP inhibitor in the neoadjuvant or adjuvant setting, if they unknown gBRCA or HER2 status, or a diagnosis of any other malignancy, not including carcinoma in situ or nonmelanoma skin cancer, within 5 years prior to data collection, they were excluded.

Investigators utilized descriptive statistics to report demographic and clinical characteristics, as well as treatment patterns and clinical outcomes. Moreover, the Kaplan-Meier method was leveraged to describe time-to-event outcomes.

To conduct statistical comparisons of clinical characteristics and outcomes between those with hormone receptor–positive, HER2-negative disease and those with TNBC, investigators used Chi-squared tests for categorical analyses. T-tests, or Wilcoxon tests, were used for continuous variables. However, the log-rank test was utilized for TTF, PFS, and time from initiation of talazoparib to chemotherapy. Notably, the analyses conducted did not adjust for differences in patient characteristics.

A total of 84 patients who received treatment from 9 community practice oncologists met the eligibility criteria for the analysis. Of the oncologists who participated in the research, approximately 44% were from small private practices defined as having 2 to 5 physicians, 22% were from medium private practices defined as having 6 to 10 physicians, and 33% were from large private practices defined as having more than 10 physicians. Fifty-six percent of oncologists were based in urban settings, 22% were based in suburban settings, and 22% were based in rural settings.

Of the 84 patients included in the study, the median age at the time of talazoparib initiation was 62 years (range, 36-91), 98% were female, and 71% were White. Moreover, 57% of patients resided in the West, 20% were from the South, 16% were from the Midwest, and 7% were from the Northeast. At the time of their diagnosis, half of patients had commercial insurance, 42% had Medicare, and 12% had Medicaid.

All patients had stage IV disease at the time that talazoparib was started. Seventy percent of patients had an ECOG performance status of 0 or 1, and 30% had a status of 2 or higher. Moreover, 19% of patients had brain metastases and 96% had visceral metastases. Sixty-four percent of patients had tumors that harbored gBRCA1 mutations, and 36% harbored gBRCA2 mutations.

Additionally, 36% had hormone receptor–positive, HER2-negative disease (n = 30), and 64% had TNBC (n = 54). Although similar distribution across sex, race, and ethnicity was noted between these 2 subsets, those with hormone receptor–positive and HER2-negative disease were observed to have a higher median age at the time of treatment initiation vs those with TNBC, at 69 years (range, 50-91) and 59 years (range, 36-79).

A significantly higher proportion of patients with hormone receptor–positive, HER2-negative disease had an ECOG performance status of 2 or higher at baseline vs those with advanced TNBC, at 47% vs 20%, respectively. However, no significant differences were noted between the subsets regarding site of disease or mutations.

Patients received talazoparib in various lines of treatment; specifically, 14% received it in the first line, 41% did so in the second line, 35% received it in the third line, and 11% received it in the fourth line.

The most common treatment regimens that were received before talazoparib included combination CDK4/6-targeted therapy and hormonal therapy (36%) and single-agent, non–platinum-based chemotherapy (36%), followed by combination platinum-based chemotherapy (25%), combination non–platinum-based chemotherapy (18%), combination immuno-oncology agent and non–platinum-based chemotherapy (17%), single-agent hormonal therapy (11%), combination hormonal therapy (10%), combination mTOR-targeted therapy and hormonal therapy (4%), combination PI3K-targeted therapy and hormonal therapy (1%), and combination immuno-oncology agent and combination platinum-based chemotherapy (1%).

Among the subset of patients with hormone receptor–positive, HER2-negative disease, the median duration of follow-up from talazoparib initiation was 9.0 months (range, 6.0-28.5). In this subset, the median PFS with the agent was 8.5 months (95% CI, 8.0-10.6), the ORR was 70% (95% CI, 52%-88%), and the median TTF was 8.6 months (95% CI, 8.0-10.6). The time from initiation of talazoparib to chemotherapy was 20.1 months (95% CI, 9.6–not evaluable).

In the TNBC subset, the median duration of follow-up from talazoparib initiation was 7.8 months (range, 2.0-33.2). The median PFS with talazoparib in this subset was 9.0 months (95% CI, 7.5-10.1), the ORR was 59% (95% CI, 45%-73%), and the TTF was a median of 8.8 months (95% CI, 7.0-10.1).

Study authors noted that the analysis may have been limited by unobserved data and missing data bias. Additionally, source document verification was not performed, although all physicians were required to submit data validation checks. Failure to correctly validate data led to exclusion from the study.

Finally, since the number of patients and oncologists included in the analysis was limited, the authors said that these findings may not be representative of all patients who have received talazoparib. “Treatment and testing patterns may not reflect those of all oncologists managing patients with locally advanced or metastatic breast cancer,” the study authors concluded.

References

1. Mahtani RL, Ivanova J, Falkenstein A, et al. Real-world patient characteristics, treatment patterns, and clinical outcomes among talazoparib-treated patients with HER2-negative, locally advanced or metastatic breast cancer and germline BRCA mutations. Presented at: 39th Annual Miami Breast Cancer Conference®; March 3-6, 2022; Miami Beach, FL.
2. Litton JK, Hurvitz SA, Mina LA, et al. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020;31(11):1526-1535. doi:10.1016/j.annonc.2020.08.2098
3. Meynard G, Villanueva C, Thiery-Vuillemin A, et al. Real-life study of BRCA genetic screening in metastatic breast cancer. Ann Oncol. 2017;28(suppl 5):V94. doi: 10.1093/annonc/mdx365.047
4. Litton JK, Rugo HS, Ettl J, et al. Abstract GS6-07: A phase 3 trial comparing talazoparib, an oral PARP inhibitor, to physician’s choice of therapy in patients with advanced breast cancer and a germline BRCA-mutation. Cancer Res. 2018;78(suppl 4):GS6-07. doi:10.1158/1538-7445.SABCS17-GS6-07