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Adding capivasertib to first-line paclitaxel improved survival in metastatic triple-negative cancer from 12.6 to 19.1 months, with the largest gain in the fifth of patients whose tumours carried a PIK3CA, AKT1 or PTEN alteration.
140 women with untreated metastatic TNBC were randomised to paclitaxel 90 mg/m2 with capivasertib 400 mg twice daily (days 2 to 5, 9 to 12, 16 to 19) or placebo. Median PFS was 5.9 versus 4.2 months (HR 0.74; one-sided P 0.06 against a 0.10 threshold) and median overall survival 19.1 versus 12.6 months (HR 0.61). In 28 patients with PIK3CA/AKT1/PTEN-altered tumours PFS was 9.3 versus 3.7 months (HR 0.30). Grade 3 or worse diarrhoea 13% versus 1%.
PAKT gives the trial-based prevalence of PI3K-pathway alteration in first-line metastatic TNBC (one in five) and the strongest signal for AKT inhibition in that subgroup; the phase 3 CAPItello-290 did not confirm it.
Shares PTEN, AKT, Capivasertib, PIK3CA / PI3K-alpha.
Shares PTEN alteration (sequencing) and PTEN loss (IHC), PTEN, AKT, PI3K / AKT / mTOR.
Shares Peter Schmid, AKT, Capivasertib, PI3K / AKT / mTOR.
Shares AKT1 E17K mutation, PIK3CA mutation, PTEN, AKT.
Shares PTEN, AKT, PIK3CA / PI3K-alpha, PI3K / AKT / mTOR.
Shares PTEN, AKT, PIK3CA / PI3K-alpha, PI3K / AKT / mTOR.
Shares PTEN, Capivasertib, PIK3CA / PI3K-alpha, Metastatic triple-negative breast cancer.
Shares PTEN alteration (sequencing) and PTEN loss (IHC), PTEN, PIK3CA / PI3K-alpha, PI3K / AKT / mTOR.