Mutations in the PIK3CA gene are present in 28-46% of patients with ER-positive, HER2-negative, advanced breast cancer, and are associated with chemoresistance and poor prognosis [1]. Alpelisib, an orally bioavailable, α-selective, PI3K inhibitor, in combination with fulvestrant demonstrated efficacy in patients with ER-positive, HER2-negative, advanced breast cancer who progressed on or after endocrine therapy [2-4]. A post-hoc analysis of the phase 3 SOLAR-1 (NCT02437318) and the phase 1 X2101 trial (NCT01219699) was performed to characterise the subset of patients deriving long-term benefit of the alpelisib plus fulvestrant combination and to identify predictors of long-term disease control. Dr Dejan Juric (Massachusetts General Hospital, MA, USA) presented the results of this post-hoc analysis.

In SOLAR-1, median progression-free survival (PFS) in the overall population randomised to alpelisib plus fulvestrant was 11.0 months versus 5.7 months in the placebo plus fulvestrant arm (HR 0.65; 95% CI 0.50-0.85; P=0.00065) [3]. The post-hoc analysis identified that 51 of 169 patients (30.2%) randomised to alpelisib plus fulvestrant achieved long-term disease control (PFS ≥18 months), with a median PFS of 33.5 months (95% CI 27.4-not reached); 22% had very long-term disease control (PFS ≥24 months). In X2101, 7 out of 52 patients (13.5%) of patients treated with alpelisib plus fulvestrant had long-term disease control (time on treatment ≥18 months) and 9.6% had very long-term disease control (≥24 months).

Using a validated support vector machine (SVM) radial model, baseline characteristics predicting (very) long-term disease control included: absence of liver and/or lung metastases, low number of metastatic sites, low ECOG performance status, presence of bone lesions only, low monocyte count, low stage at initial diagnosis, endocrine sensitivity, PR positivity with/without ER positivity. Items that did not predict long-term disease control included: poor prognosis, diabetes/pre-diabetes at baseline, heavy pre-treatment. Dose reductions –if necessary to manage adverse events– did also not preclude long-term disease control.

“In conclusion, this post-hoc analysis supports that alpelisib plus fulvestrant is a valid treatment approach for patients with ER-positive, HER2-negative, PIK3CA-mutated, advanced breast cancer, and the data demonstrate the opportunity for and possibility of long-term disease control,” said Dr Juric.

1. Mosele F, et al. Ann Oncol. 2020;31:377-386.

2. André F, et al. N Engl J Med 2019;380:1929-1940.

3. André F, Ann Oncol. 2021;32:208-217.

4. Juric D, et al. JAMA Oncol. 2019;5(2):e184475.

5. Juric D, et al. Long-term (LT) disease control in patients (pts) with hormone receptor-positive (HR+), PIK3CA-altered advanced breast cancer (ABC) treated with alpelisib (ALP) + fulvestrant (FUL). ASCO 2021 Virtual Meeting, abstract 1054.

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Fuente:  Medicom Medical Publishers