KEY TAKEAWAYS
- The study aimed to assess the safety and efficacy of combining IPAT and HP in PIK3CAmut HER2+ ABC.
- The results concluded that IPAT 400mg + HP after CT had acceptable safety and promising efficacy in PIK3CAmut HER2+ ABC.
In the CLEOPATRA trial, individuals with HER2+ PIK3CAmut advanced breast cancer (ABC) experienced shorter progression-free survival (PFS) compared to those with PIK3CAwt.
Ana Mafalda Antunes De Melo e Oliveira and the team aimed to investigate whether combining IPAT, an AKT inhibitor active in PI3K/AKT-altered tumors, with HP is safe and effective in PIK3CAmut HER2+ ABC.
The study examined the safety and efficacy of IPAT + HP in patients with PIK3CAmut HER2+ ABC eligible for maintenance HP after discontinuing first-line chemotherapy (CT) for reasons other than progressive disease.
The primary objective was to establish the maximum tolerated dose (MTD) of IPAT + HP, defined as the highest dose at which ≤1 of the first 6 participants experienced dose-limiting toxicity (DLT: grade [G] ≥3 diarrhea >72 hours, G ≥2 diarrhea >5 days [d], other treatment-related adverse events [TRAEs] G ≥ 3) during the initial 28-day treatment period. The initial IPAT dose was 400mg d1-21 in 28-day cycles with standard dose HP (de-escalation doses are 300mg and 200mg). Secondary objectives included safety, overall response rate (ORR), clinical benefit rate (CBR), and progression-free survival (PFS).
The results revealed that PIK3CAmut was detected in 24 out of 108 HER2+ tumors (22%). Between February 2020 and November 2023, 17 participants were enrolled, with a median age of 54 (range: 41-78). The majority had hormone receptor-negative tumors, visceral metastases, and stage IV disease at diagnosis (59% each). As of the data cut-off in April 2024, 6 participants (35%) remained on treatment. No dose-limiting toxicities (DLTs) were observed in the first 6 participants, establishing IPAT 400mg + HP as the maximum tolerated dose (MTD).
Among the remaining 11 participants, 3 experienced a DLT (grade 3 diarrhea, grade 3 vomiting, and grade 3 rash). The most common treatment-related adverse events (TRAEs) included diarrhea (82%), nausea (47%), decreased appetite (35%), fatigue, rash, and vomiting (29% each). Grade 3/4 TRAEs occurred in 35% of participants, with diarrhea and nausea being the most common (12% each). With a median follow-up of 19.9 months, the confirmed ORR was 31%, CBR was 69%, and the median PFS was 15.4 months (range: 9.4-not reached), with 48% of participants progression-free after 18 months from enrollment.
The study concluded that maintenance therapy using IPAT 400mg + HP after chemotherapy demonstrated an acceptable safety profile and promising efficacy in individuals with PIK3CAmut HER2+ ABC. Further evaluation of combining a PI3K/AKT pathway inhibitor with anti-HER2 treatment in this context is warranted.
The trial was sponsored by the SOLTI Breast Cancer Research Group.
Source: https://cslide.ctimeetingtech.com/breast24hybrid/attendee/confcal/show/session/40
Clinical Trial: https://clinicaltrials.gov/study/NCT04253561
Antunes De Melo e Oliveira AM, Ciruelos EM, Morales Murillo-S, et al. (2024). “SOLTI-1507 IPATHER: Primary results of the phase Ib study of ipatasertib (IPAT) and dual anti-HER2 therapy with trastuzumab and pertuzumab (HP) in patients (pts) with PIK3CA mutant (mut) HER2+ advanced breast cancer (ABC).” Presented at ESMO-BC 2024 (LBA3, ID 41)
