Capivasertib Combo Is Best Suited to Pathway-Altered Advanced Breast Cancer
Additional research is needed to confirm whether capivasertib/fulvestrant offers increased benefit in patients with locally advanced or metastatic breast cancer not harboring AKT pathway alterations.
With the approval of capivasertib plus fulvestrant in hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer, Paolo Tarantino, MD, raised the question of whether the combination is best used in those with AKT pathway alterations due to previously reported robust benefit or if use should extend to the overall population.1
Tarantino, a medical oncologist at Dana-Farber Cancer Institute, discussed how patients with AKT and PIK3CA pathway alterations would benefit the most from this treatment. As new data are released, it should be determined whether there is a benefit in the overall population, as well, he explained.
Results were observed in the phase 3 CAPItello-291 trial (NCT04305496) with the median progression-free survival (PFS) in the combination group was 7.2 months vs 3.6 months in the placebo group (HR, 0.60; 95% CI, 0.51-0.71; P <.001).2 For patients who had an AKT pathway alteration, the median PFS was 7.3 months in the combination group vs 3.1 months in the placebo group (HR, 0.50; 95% CI, 0.38-0.65; P <.001).
Transcript:
In general, seeing a doubling of progression-free survival with the addition of capivasertib to fulvestrant justifies the use of this combination. The main question that I have in mind is whether to use this combination only for patients with alterations in the PIK3CA, AKT P10 pathway or to extend it to the overall population where there seems also to be a numerical benefit. Once again, updates of the data and a close look at the curves can help to understand [the benefit].
The majority of the benefit was seen in about 40% of the patients who had an alteration in the pathway. Personally, with the current data that we have, I would be more strongly encouraged to utilize the combination of fulvestrant plus capivasertib in patients with pathway-altered disease. Whereas in patients without detected alterations in the pathway, I do feel that there is also potentially activity of capivasertib, but we also need to study that deeper to understand what the mechanism is and if the activity of the drug justifies the [adverse] effects in that setting.
References
- FDA approves capivasertib with fulvestrant for breast cancer. News release. FDA. November 16, 2023. Accessed November 16, 2023. https://shorturl.at/abtH8
- Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med. 2023;388(22):2058-2070. doi:10.1056/NEJMoa221413
