Capivasertib Combo Does Not Meet OS End Points in Advanced TNBC

"While the CAPItello-290 trial [NCT03997123] results have not shown what we hoped, they provide important information to further understand this aggressive form of breast cancer where patients are in urgent need of new treatments," according to Peter Schmid, MD.

Combining capivasertib (Truqap) with paclitaxel did not improve overall survival (OS) vs placebo plus paclitaxel among patients with locally advanced or metastatic triple-negative breast cancer (TNBC), according to a press release on results from the phase 3 CAPItello-290 trial (NCT03997123).¹

Specifically, the capivasertib combination failed to reach one of the dual primary end points of OS across the overall trial population as well as a subgroup including those with PIK3CA, AKT1, or PTEN alterations.

The safety profile of capivasertib in the CAPItello-290 trial was comparable with prior reports of the agent in this patient population, and investigators identified no new safety signals. Further findings will be presented in the future.

“Despite modest advances, [TNBC] remains one of the most challenging forms of disease to treat due to the lack of known actionable biomarker targets, and chemotherapy-based regimens continue to be the mainstay of treatment,” lead trial investigator Peter Schmid, MD, a medical oncologist at Barts Cancer Institute of Queen Mary University of London, said in the press release.¹ “While the CAPItello-290 trial results have not shown what we hoped, they provide important information to further understand this aggressive form of breast cancer where patients are in urgent need of new treatments.”

In the double-blind, phase 3 CAPItello-290 trial, 923 adult patients with histologically confirmed advanced or metastatic TNBC were assigned to receive capivasertib or placebo in combination with paclitaxel. Investigators administered capivasertib at 400 mg on days 2 to 5 of weeks 1, 2, and 3 followed by 1-week off-treatment for each 28-day cycle.² Additionally, patients received paclitaxel at 80 mg/m² for 3 consecutive weekly infusions.

The trial’s secondary end points included progression-free survival (PFS), overall response rate, clinical benefit rate, duration of response, safety and tolerability, pharmacokinetics, and health-related quality of life.

Patients 18 years and older with histologically confirmed TNBC that was metastatic or locally recurrent and not amenable to curative resection were eligible for enrollment on the trial. Additional eligibility criteria included having an ECOG or World Health Organization performance status of 0 or 1, measurable disease based on RECIST v1.1 guidelines, and availability of formalin-fixed paraffin-embedded tumor samples from primary or recurrent disease.

Those with prior chemotherapy in the neoadjuvant or adjuvant setting within 6 months prior to randomization or prior systematic therapy for inoperable locally advanced or metastatic disease were unable to enroll on the trial.

“We are committed to advancing science for patients in some of the most challenging cancers, including this heterogeneous subtype of breast cancer. While we are disappointed in the CAPItello-290 outcome, these results will further our understanding of the role of the PI3K/AKT pathway in breast cancer as we continue our clinical research across the [capivasertib] clinical development program and across our pipeline,” Susan Galbraith, executive vice president of Oncology Research & Development at AstraZeneca, the developers of capivasertib, said in the press release.¹

The FDA previously approved capivasertib plus fulvestrant (Faslodex) for previously treated, locally advanced or metastatic, hormone receptor–positive, HER2-negative breast cancer with at least 1 PIK3CA, AKT1, or PTEN alteration in November 2023.³ Supporting data for this approval came from the phase 3 CAPItello-291 trial (NCT04305496), in which capivasertib/fulvestrant elicited a median PFS of 7.3 months (95% CI, 5.5-9.0) vs 3.1 months (95% CI, 2.0-3.7) with placebo/fulvestrant among 289 patients with at least 1 of the aforementioned alterations (HR, 0.50; 95% CI, 0.38-0.65; P <.0001).

Japan’s Ministry of Health, Labour, and Welfare also approved capivasertib/fulvestrant for the same patient population in March 2024 based on findings from CAPItello-291.⁴

References

1. Update on the CAPItello-290 phase III trial for Truqap plus chemotherapy in advanced or metastatic triple-negative breast cancer. News release. AstraZeneca. June 18, 2024. Accessed June 19, 2024. https://tinyurl.com/47zjy3d8
2. Capivasertib+paclitaxel as first line treatment for patients with locally advanced or metastatic TNBC (CAPItello-290). ClinicalTrials.gov. Accessed June 19, 2024. https://tinyurl.com/57r545y6
3. FDA approves capivasertib with fulvestrant for breast cancer. News release. FDA. November 16, 2023. Accessed June 19, 2024. https://tinyurl.com/4rc8w8xn
4. Truqap plus Faslodex approved in Japan for patients with advanced HR-positive breast cancer. News release. AstraZeneca. March 27, 2024. Accessed June 19, 2024. https://tinyurl.com/3ps6pepp