SAN ANTONIO -- Adding the investigational agent ipatasertib to paclitaxel failed to improve progression-free survival (PFS) in patients with PIK3CA/AKT1/PTEN-altered advanced triple-negative breast cancer, a researcher reported.
PFS came in at 7.4 months with the AKT inhibitor plus paclitaxel versus 6.1 months with placebo plus paclitaxel (P=0.9237) at a follow-up of 8.3 months, according to Rebecca Dent, MD, of the National Cancer Center Singapore.
Also in the phase III IPATunity130 Cohort A trial, the overall response rate was 39% in the ipatasertib-paclitaxel cohort versus 35% in the placebo-paclitaxel group, while 55% of the patients in both the study-agent arm (n=168) and placebo arm (n=87) experienced progression events, and the clinical benefit rates were 49% and 45%, respectively, she reported at the San Antonio Breast Cancer Conference (SABCS) virtual meeting.
While the adverse-event (AE) profile was similar for both groups, with no new serious AEs identified, there was an increase in therapy-induced diarrhea among patients on ipatasertib, Dent noted.
Overall survival follow-up is ongoing, according to Dent. Results from the trial's Cohort B were presented at the 2020 European Society of Medical Oncology virtual meeting.
SABCS program planning co-chair Carlos Arteaga, MD, of the Simmons Comprehensive Cancer Center at the University of Texas Southwestern School of Medicine in Dallas, pointed out that "PIK3CA mutations, ATK1 mutations, and PTEN mutations are not necessarily the same," and questioned if the study had enough patients with ATK1 mutations to rule out that the subgroup benefited.
Dent replied she thought there were a number of patients in the trial with ATK1 mutations, but suggested that would be addressed in future analyses of the study.
The researchers recruited patients with advanced triple-negative breast cancer (TBNC) who had alterations to the PIK3CA/AKT1/PTEN genes. About 35% of patients with TNBC harbor these alterations, making treatment with an AKT inhibitor an attractive way of attacking the disease.
"The PIK3CA/AKT1 pathway is vital to cellular metabolism, proliferation, and invasion," Dent said. "It has also been increasingly recognized that AKT may be a master regulator of this pathway. AKT can be activated by loss of function negative regulators, gain of function positive regulators, but most importantly there can be a therapy-induced survival response, specifically through upregulation of AKT in the presence of chemotherapy or endocrine therapy."
Ipatasertib is an oral ATP-competitive selective inhibitor of AKT1/2/3 that was used with success in the phase II LOTUS trial, which showed a PFS advantage among patients with TNBC and targeted genetic alterations, according to Dent, but those same benefits were not seen in the current trial.
Eligible patients for the current trial had to have measurable TNBC, had to be naive to chemotherapy, and had to be at least 12 months out from adjuvant treatments. Trial participants were similar in age (56 in the study-agent arm; 53 in the placebo arm) and about 40% were recruited from sites in Europe. About 80% had metastatic disease (40% with lungs metastases; 33% with bone metastases), while the remainder had locally advanced TNBC. Patients were stratified by age, region of treatment, status of prior chemotherapy, length of time of the interval since chemotherapy and advanced cancer diagnosis, mutation, and other tumor characteristics.
Dent said she and her colleagues will continue to analyze results in the Cohort A "to explore potential biomarkers of benefit from ipatasertib."
Disclosures
The trial was supported by Roche/Genentech.
Dent disclosed relevant relationships with Roche, Novartis, Lilly, Pfizer, Eisai, Merck and AstraZeneca.
Arteaga disclosed relevant relationships with Novartis, Lilly, TAIHO Oncology, Pfizer, Takeda, PUMA Biotechnology, Bayer, Daiichi Sankyo, Merck, AstraZeneca, OrigiMed, Immunomedics, ARVINAS, Sanofi, Athenex, Provista, and Y-TRAP.
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