The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

At the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, researchers presented phase 2 data on the activity of the PARP inhibitor talazoparib in patients with advanced HER2-negative breast cancer and other solid tumors that lacked BRCA1/2 mutations.

Among the patients in this single-institution study, all received 1 prior course of platinum therapy with no progression on or within 8 weeks of the last dose. In addition, participants had to have measurable disease at the time of enrollment, and the germline or somatic alterations in homologous recombination (HR) pathway genes of the tumors could not be BRCA1/2.

Of the 20 patients (median age of 54 years), 13 had breast cancer (1 triple-negative breast cancer [TNBC], 12 HR+/HER2-), and the other 7 had cancer of the colon, pancreas, testicles, uterus, or parotid gland.

Patients were administered talazoparib (1 mg daily) until disease progression; researchers measured response rates approximately every 8 weeks.

Results appeared most promising in patients with breast cancer. Of 13 evaluable patients with breast cancer, the overall response rate [ORR] was 31%.

Seven patients had stable disease [SD] for 6 months or longer (clinical benefit rate [CBR], 54%). No responses were seen in nonbreast tumors (0% ORR); although 2 patients (1 with testicular cancer, 1 with colon cancer) had SD of 6 months or longer, which translated into a CBR of 29% in patients with nonbreast cancers.

The investigators reported good tolerability with talazoparib; dose reductions were required for 5 patients who experienced hematologic toxicity.

The researchers also determined that those with a germline PALB2 mutation (6 of 6 patients, 100%) had tumor regression from baseline, making this mutation a “promising biomarker for talazoparib response.”

In conclusion, the authors wrote, “In this proof-of-concept phase 2 study, single-agent talazoparib demonstrated activity in HER2-negative advanced breast cancer pts with a HR pathway mutation beyond BRCA1/2. Further evaluation of talazoparib in this population is warranted.”

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

Reference

Gruber JJ, Afghahi A, Hatton A, et al. Talazoparib beyond BRCA: A phase II trial of talazoparib monotherapy in BRCA1 and BRCA2 wild-type patients with advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous recombination (HR) pathway genes. Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 3, 2019; Chicago, IL. Abstract 3006.