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The 812-patient trial in which adding the AKT inhibitor capivasertib to first-line paclitaxel did not lengthen life in metastatic triple-negative breast cancer (17.7 versus 18.0 months), even in the 31 percent of patients whose tumours carried the pathway alterations it targets.
CAPItello-290 (Schmid, McArthur, Cortés, Xu and colleagues) randomised 812 patients with previously untreated metastatic triple-negative breast cancer between July 2019 and February 2022 to paclitaxel 80 mg/m2 on days 1, 8 and 15 of a four-week cycle plus capivasertib 400 mg or placebo twice daily on days 2 to 5 of each treatment week, following the positive phase 2 PAKT trial; 30.7 percent had PIK3CA, AKT1 or PTEN alterations by retrospective central testing. Dual primary endpoints were overall survival overall and in the altered group. At final analysis (18 March 2024) median overall survival was 17.7 versus 18.0 months (hazard ratio 0.92, 95 percent confidence interval 0.78 to 1.08, p=0.3239) and 20.4 months in both arms of the altered group (1.05, 0.77 to 1.43). Median progression-free survival numerically favoured capivasertib (5.6 versus 5.1 months, 0.72, 0.61 to 0.84; altered group 7.5 versus 5.6, 0.70). Grade 3 or higher diarrhoea occurred in 12.7 versus 0.7 percent, capivasertib was stopped for adverse events in 8.5 percent, and adverse events led to death in 4.2 percent of all patients.
The latest in a line of negative targeted-therapy trials in triple-negative disease (EGFR, VEGF, iniparib, now AKT): a modest delay in progression that did not translate into survival, in the same year that an antibody-drug conjugate did. It is why the roadmap treats pathway-targeted small molecules as the road not taken.
Shares Peter Schmid, Javier Cortés, Annals of Oncology, Progression-free survival (PFS) and the tag tnbc-evidence.
Shares Annals of Oncology, Overall survival (OS), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, AstraZeneca and the tag tnbc-evidence.
Shares Annals of Oncology, Overall survival (OS), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, AstraZeneca and the tag tnbc-evidence.
Shares Annals of Oncology, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Paclitaxel / nab-paclitaxel, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Tumour heterogeneity and clonal evolution, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Javier Cortés, Annals of Oncology, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Tumour heterogeneity and clonal evolution, PI3K / AKT / mTOR, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Annals of Oncology, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.