Survival Bomb with Palbociclib in HR + Breast Cancer

MUNICH – Median survival in patients treated with palbociclib cyclin-dependent inhibitor (CDK) 4/6, an advanced hormone receptor-positive inhibitor (HR +), was improved by 10 months in addition to hormone therapy, randomized trial shown .

In the overall study population, the median survival rate increased by 28.0 months with fulvestrant (Faslodex) alone, a hormonal agent, at 34.9 months with the combination. However, the difference did not reach statistical significance.

In addition, the subgroup of patients who responded to previous hormonal therapy showed a statistically significant improvement in median survival after 10 months with the Palbociclib regimen, increasing to 11 months in patients without visceral metastases.

The results provided reassurance on the potential for improved survival of CDK 4/6 inhibitors, which was lacking in the three approved agents of the class, Massimo Cristofanilli, MD, from Robert H. Lurie Comprehensive. Cancer Center in Chicago. , said here at the annual congress of the European Society of Medical Oncology.

The study was published simultaneously by the New England Journal of Medicine.

"This is the first report showing that the absolute survival gain is similar to the absolute gain in progression-free survival across the entire population," said Cristofanilli. "In addition, this prolongation of life is of great magnitude in patients with prior sensitivity to endocrine therapy."

"We now have reliable data suggesting that this treatment should be the new standard of care," he added.

Although the difference in survival has not reached statistical significance, oncologists will likely agree that a survival gain of nearly 7 months is clinically significant, said Cristofanilli.

Speculation about the ability of CDK 4/6 inhibitors to improve their survival has been a "hot issue," said Carmen Cristofanilli, MD, of the European Institute of Oncology in Milan. Although the results of PALOMA-3 provided the first evidence of improvement in survival, the study did not fully solve the problem.

"The study was undernourished for overall survival, so the data should be interpreted with caution," she said. "Although the results strongly suggest that the PFS [progression-free survival] Benefit may result in overall benefit in terms of survival; other trials with CDK 4/6 inhibitors will help confirm the survival benefit estimate observed in this study. "

The three approved CDK 4/6 inhibitors – palbociclib, ribociclib (Kisqali) and abemaciclib (Verzenio) – have become the standard of care for patients with advanced breast cancer, HR + / HER2. In the randomized phase III trials, the three drugs showed a statistically significant improvement in progression-free survival (PFS) when they were added to standard endocrine therapy, compared with endocrine therapy alone. However, data showing that drugs improved overall survival were lacking.

Cristofanilli presented the results of an updated analysis of the randomized phase III trial of PALOMA-3 comparing the combination of palbociclib-fulvestrant with fulvestrant-placebo in 521 patients whose disease had progressed after one year. initial endocrine treatment. The first analysis, published in 2016, showed that the median PFS combination had more than doubled.

Overall survival was an essential secondary endpoint, but at the time of the release of the SSP results, survival data were too immature to allow meaningful analysis. Cristofanilli reported results of a median follow-up of 44.8 months.

In accordance with the test protocol, the investigators conducted a stratified analysis of the survival data, taking into account the previous sensitivity of the patients to hormone therapy, the presence or absence of metastases visceral, menopausal status, the effect of subsequent treatment after the course of disease and safety. The analysis showed that the survival difference of 6.9 months resulted in a 19% reduction in the survival risk ratio (95% CI 0.64 to 1.03). An unstratified analysis resulted in a 21% reduction in the risk ratio (95% CI: 0.63-1.00).

Researchers conducted several subgroup analyzes to identify patients benefiting most from the addition of the CDK 4/6 inhibitor to endocrine therapy. An analysis of 410 patients whose disease was sensitive to previous endocrine treatment showed an overall median survival of 39.7 months, compared to 29.7 months with fulvestrant alone (HR 0.72 for death, 95% CI 0, 55-.94). Among patients not sensitive to first-line endocrine therapy (endocrine resistance), median overall survival was 20.2 months with palbociclib and 26.2 months with fulvestrant alone.

The study population included 201 patients who had no visceral metastases at the time of enrollment. They had a median survival of 46.9 months with the combination palbociclib against 35.4 months with fulvestrant alone (HR 0.69 for death, 95% CI 0.46-1.04, P= 0.44). Postmenopausal women (N = 413) were better off with the combination (34.8 vs 27.1 months) than the premenopausal women (38.0 months in both treatment groups).

2018-10-25T14: 30: 00-0400