The phase III CAPItello-290 trial assessed the combination of capivasertib (C) with paclitaxel (P) as a first-line treatment for metastatic triple-negative breast cancer compared to paclitaxel plus placebo. A total of 812 patients were enrolled, with 30.7% showing PIK3CA/AKT1/PTEN alterations. While progression-free survival slightly favoured the C+P combination, the primary endpoint of overall survival was not met in either the overall population or the altered gene subgroup. Common adverse events included diarrhoea and anaemia, with a manageable safety profile. Further research is needed to explore the clinical potential.
Disclosures: Prof. Heather McArthur discloses that she has acted as a consultant for Amgen, AstraZeneca, Bristol-Myers Squibb, Calithera, Celgene, Daiichi-Sankyo, Delcath, Eli Lilly, Genentech/Roche, Gilead, Immunomedics, Merck, Moderna, Novartis, OBI Pharma, Peregrine, Pfizer, Puma, Seattle Genetics, Spectrum Pharmaceuticals, Stemline, Syndax Pharmaceuticals, and TapImmune; and has received grant/research support from Bristol-Myers Squibb; MedImmune, LLC/AstraZeneca; BTG; and Merck.
Transcript
My name is Heather McArthur, and I’m the Clinical Director of Breast Cancer at UT Southwestern Medical Center, Dallas, TX, USA. At the recent ESMO 2024 meeting in Barcelona, Spain, I had the privilege of presenting on behalf of my colleagues and coinvestigators the results of the CAPItello-290 phase III trial that was a study looking at capivasertib with paclitaxel as first-line therapy for metastatic triple-negative breast cancer.
Capivasertib is an oral potent selective inhibitor of all three AKT isoforms. It’s currently recommended in combination with fulvestrant for ER+ advanced disease that has progressed. The PI3K/AKT signaling pathway is often overactivated in breast cancer, thereby promoting breast cancer cell survival and resistance to chemotherapy. And preclinical data showed that capivasertib together with paclitaxel decreased cell proliferation and increased cell death and triple-negative breast cancer specifically. The randomized phase II LOTUS and PACT studies provided rationale for this phase III effort. In both studies progression-free survival and overall survival favoured outcomes for patients with AKT inhibitor together with paclitaxel over placebo with paclitaxel.
So here we present the phase III results from the randomized CAPItello-290 study looking at the efficacy of capivasertib together with paclitaxel versus placebo with paclitaxel. So in this study, 812 patients were randomized to receive paclitaxel with either capivasertib or placebo. Men and women were eligible if they were eligible to receive taxane. They could not have received any prior therapy for advanced disease, and they could not have received prior curative intent therapy within the preceding six months or twelve months for taxane. They had to have good performance status, hemoglobin <8% and patients who had non-insulin dependent diabetes could participate.
There were two dual primary endpoints for this study, overall survival in the overall population and the second endpoint of overall survival in the PIK3CA/AKT1/PTEN altered population.
Just to go over a few baseline characteristics: the median age was 54 years, all participants were women, about 2/3 of patients were post-menopausal, the body mass index average was 26, 3% patients were enrolled in the US, 2% in China, so 95% of patients were enrolled in the rest of the world. More than 2/3 of patients had visceral disease. Approximately 40% of patients had de novo metastatic disease. About 15% percent of patients had PDL-1 positive disease, and only four patients participating in this trial had prior immune therapy, presumably in the curative intent setting.
The alteration frequency was consistent with the literature in that most patients had PIK3CA and/or PTEN alterations. The bottom line from this study was that there was no statistically significant improvement in overall survival with the addition of capivasertib to paclitaxel as first-line therapy for metastatic triple-negative breast cancer when compared with placebo with paclitaxel in either the overall population or in the PIK3CA/AKT1/PTEN altered population and interrogating subgroups. There was no specific subgroup to which a benefit could be attributed. And looking at key secondary endpoints, progression-free survival, there was a, numerically favored improvement in progression-free survival 0.5 months in the overall population and just under two months in the tumour altered population.
The most common toxicity, not surprisingly, with the combination was diarrhoea, 76% percent incidence of diarrhoea, with most of that being grade one or two, consistent with known toxicity profile of this agent. Approximately 22% percent of patients had hyperglycemia, which is also a known side effect with this class of agents. Again, most of them were grade one or grade two.
So in conclusion, Capitello two ninety was conducted in response to phase II PACT and LOTUS studies. The dual primary endpoints of overall survival in the overall population and in the patient population with PIK3CA/AKT1/PTEN altered tumours failed to meet the pre-specified boundary for statistical significance. There was a numerical trend in favour of progression-free survival and overall response rate in favour of capivasertib. But overall, this was a negative study, and the industry sponsor announced that they would not be pursuing this asset in the triple-negative breast cancer space. However, efforts in ER+ disease continue and will be unaffected by this data.
Interviewer/Editor: Sophie Nickelson
This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the European Society of Medical Oncology (ESMO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Cite: McArthur H. Capivasertib + Paclitaxel for metastatic triple-negative breast cancer did not meet threshold for improving overall survival. touchONCOLOGY. October 10, 2024.
