Novartis’ targeted therapy flips expectations in advanced breast cancer

Challenging expectations for a targeted therapy approach, standard chemotherapy demonstrated superior tolerability and a longer progression-free survival (PFS) compared with Novartis’ PI3Kα inhibitor Piqray (alpelisib) in patients with hormone-receptor positive (ER+) HER2-negative advanced breast cancer.

The findings emerge from the CAPTURE breast cancer study led by Breast Cancer Trials across Australia and New Zealand. The study explored whether patients with ER-positive metastatic disease could benefit from a novel drug combination intended to improve PFS after progression on CDK4/6 inhibitors plus aromatase inhibition, with PIK3CA mutations identified as a key therapeutic target through circulating tumour DNA (ctDNA).

“About 70% of breast cancers are ER-positive,” explained Professor Sarah Jane Dawson, medical oncologist at Peter MacCallum Cancer Centre and study chair of the CAPTURE trial. “Endocrine (hormone) treatments for these cancers have been effective, but in advanced disease, the cancer eventually becomes resistant to initial endocrine treatment and the treatment is no longer effective, so we need other ways of treating these resistant cancers.”

Results from the trial were presented at the American Society of Clinical Oncology Annual Meeting (ASCO), providing a comparison between Piqray-based therapy and standard chemotherapy.

“While it was hoped that this treatment would result in greater reduction of the growth of breast cancer for these patients, the trial showed that the outcomes were not superior to the current standard of care, which we know is an effective, well-tolerated option. This suggests that we need to identify better targeted therapies,” said Professor Dawson.

Median PFS was 7.4 months for Piqray (alpelisib) + fulvestrant versus 9.4 months for capecitabine (p=0.45). In patients with visceral disease, median PFS was 5.4 months for Piqray + fulvestrant compared with 12.1 months for capecitabine. Toxicity profiles also diverged significantly with 79.3% of patients receiving Piqray + fulvestrant experiencing grade 3/4 adverse events versus 46.2% in the capecitabine arm.

“We learn something from every trial. The next step is to use translational research from the tissue samples collected during CAPTURE to identify which of these patients may be best suited to the new therapy,” stated Professor Dawson. “The aim is to get the best treatment to the right person at the right time. Having blood based tests where we can identify which patients are most likely to respond to these therapies would be a huge step forward.”

Dr Nick Zdenkowski, Medical Advisor to Breast Cancer Trials, said “This trial supports continued use of oral chemotherapy that is cost-effective and well-tolerated when compared with alpelisib [Piqray]. The role of Breast Cancer Trials is to identify what we can do well, including academic independent trial design, considering the cost implications, and quality of life in the short term and long term – it’s not always about adding a more expensive treatment.”

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