Suzette Delaloge, MD, MSc
Commenting on the final overall survival analysis of the LOTUS trial, the study’s invited discussant, Suzette Delaloge, MD, MSc, Chair of the Breast Cancer Group at the Institut Gustave Roussy, Paris, said: “We see there might also be an overall survival effect with ipatasertib and paclitaxel…. It’s quite amazing and very impressive.” She suspects the lack of statistical significance is attributable to the small number of patients.
Dr. Delaloge noted the lack of significance in the intent-to-treat population and in the altered-tumor subset stands in contrast to the findings of the phase III PAKT trial of capivasertib.1 This similar study demonstrated a statistically significant survival benefit in both the intent-to-treat population (hazard ratio [HR] = 0.61; 95% confidence interval [CI] = 0.37–0.99; P = .04) and in patients with altered tumors (HR = 0.30; 95% CI = 0.11–0.79; P = .01). Both the PAKT and LOTUS trials found significant benefits in progression-free survival.
“For the intent-to-treat populations of the two studies, the progression-free survivals were very similar, and in the altered populations, we saw a striking effect and similar hazard ratios in both studies. However, in terms of overall survival, we have no significant difference in LOTUS but a significant finding in PAKT,” Dr. Delaloge commented. “This is puzzling…. The data are early, but it looks like the effect could be important.”
Why Do Overall Survival Data Differ?
Dr. Delaloge considered one possible explanation of the overall survival differences between the two studies: the heterogeneity of triple-negative tumors. “It’s important for phase III trials to involve extensive genomic definitions of the tumor, so we understand what we are talking about and what the real effect of the drug is,” she said.
Emphasizing the value of inhibiting AKT in combination with paclitaxel, Dr. Delaloge suggested its efficacy may not be in PIK3CA/AKT-altered tumors. It is important to pursue this approach, potentially in combination with other strategies, and even in earlier phases of disease, she added.
DISCLOSURE: Dr. Delaloge has received travel funding from AstraZeneca, Pfizer, Roche, and Pierre Fabre.
1. Schmid P, Abraham J, Chan S, et al: Capivasertib plus paclitaxel vs placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: The PAKT trial. J Clin Oncol 38:423-433, 2020.
In the phase II LOTUS trial, the addition of the AKT inhibitor ipatasertib to paclitaxel in the first-line treatment of patients with advanced triple-negative breast cancer yielded a strong numerical improvement—a median gain of 9 months—in overall survival, in the final survival analysis reported...