Abemaciclib + fulvestrant survival benefit extends to Asians with HR+, HER- ABC

Adding the CDK4/6 inhibitor abemaciclib to an endocrine therapy of fulvestrant extends overall survival (OS) compared with fulvestrant alone in East Asian patients with hormone receptor-positive (HR+), HER2-negative advanced breast cancer (ABC) who have progressed on prior endocrine therapy, consistent with results from the overall population, updated analysis of the global, phase III MONARCH 2 study has shown. 

Previously, the primary analysis on an intent-to-treat (ITT) population of 669 participants showed significant improvements in progression-free survival (PFS) and OS with the addition of abemaciclib vs fulvestrant alone.

The current study, presented during the ESMO Asia 2020 Congress, reported on the survival data for a subset of 212 East Asian women (from Japan, South Korea, and Taiwan), who were randomized 2:1 to receive abemaciclib + fulvestrant or fulvestrant alone. [ESMO Asia 2020, abstract 45O]

As of data cutoff, the median OS was not reached in the combination therapy arm compared with 48.9 months in the fulvestrant alone arm (hazard ratio [HR], 0.798; p=0.38) — a survival benefit that was consistent with that in the ITT population (HR, 0.76; p=0.01).    

At 42 months follow-up, 64 percent of the East Asian patients receiving abemaciclib + fulvestrant were still alive compared with 53 percent in those treated with fulvestrant alone. Similarly, the corresponding OS rates in the ITT population were 53.8 percent vs 44.6 percent, respectively.

“Consistent with previous reports in the ITT population, abemaciclib + fulvestrant was an effect treatment for women in East Asia with HR+, HER2-negative ABC whose disease has progressed on prior endocrine therapy,” said lead author Dr Huang Chiun-Sheng of the National Taiwan University Hospital in Taipei, Taiwan, who presented the findings during the recent ESMO Asia 2020 virtual congress. 

“Continued follow-up is ongoing to further characterize OS benefit and exploratory efficacy endpoints,” he added.

PFS data for the East Asian subset have previously been reported elsewhere, at a median of 21.2 months for abemaciclib + fulvestrant vs 11.6 months for fulvestrant alone (HR, 0.520; p<0.001) —which was again consistent with the ITT population (median, 16.4 vs 9.3 months; hazard ratio [HR], 0.55; p<0.0001). [Ann Oncol 2017;doi:10.1093/annonc/mdx654.004; J Clin Oncol 2017;35:2875-2884]

In the current updated analysis, the addition of abemaciclib also led to significantly delayed second objective disease progression compared with fulvestrant alone (median, 26.1 vs 21.6 months; HR, 0.59; p=0.001).

Accordingly, time to chemotherapy (median, 51.5 vs 22.1 months; HR, 0.601; p=0.008) and chemotherapy-free survival (median, 30.9 vs 21.6 months; HR, 0.573; p=0.002) were significantly improved, both in favour of the combination therapy.

“Abemaciclib significantly delayed the receipt of subsequent chemotherapy as well as second disease progression in East Asians,” reported Huang.  

There were no new safety signals in the updated analysis, with the safety profile being broadly comparable with those that have been previously reported in this subset of East Asian patients. 

“While certain toxicities such as neutropenia and leukopenia were more frequent in the East Asian patients compared with the ITT population, the safety profile in East Asian patients was manageable and generally consistent with the ITT population,” Huang noted.