Ribociclib Has Similar Benefits for Elderly Patients With Breast Cancer

Ribociclib had similar clinical benefits and safety profiles for both elderly and younger patients with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer, according to findings from a pre-planned subgroup analysis of data from the MONALEESA-2 trial.

These data point to a shift in paradigm for the future management of these patients, from the current standard of care, Femara (letrozole), to a combination regimen of Femara plus ribociclib. These results were presented at the 19th European Cancer Congress (ECCO 2017).

"At some point, all breast cancers become resistant to endocrine therapy. The addition of targeted agents may extend the treatment benefit derived from endocrine therapy and delay disease progression,” according to Gabe S. Sonke M.D., Ph.D., of the Netherlands Cancer Institute and BOOG Study Center in the Netherlands.

MONALEESA-2 is a randomized international, double blind phase 3 trial of ribociclib plus the aromatase inhibitor Femara. The study demonstrated improved progression-free survival (PFS) over Femara alone in treatment-naïve post-menopausal women with advanced HR+ metastatic breast cancer.

In the overall population of patients, a 44 percent improvement in PFS was demonstrated with ribociclib plus Femara as a frontline therapy over placebo/ Femara. The median PFS was not reached in the study arm at data cutoff, compared to 14.7 months in the placebo arm. In patients with measurable disease who received ribociclib, the overall response rate (ORR) was 52.7 percent, compared to 37.1 percent in those receiving Femara alone.

In the subgroup of 295 MONALEESA-2 patients aged 65 or more years having a median age of 71 years (range, 65-91), 150 patients received 2.5 mg daily of ribociclib plus 2.5 mg daily of Femara and 145 patients received placebo plus 2.5 mg daily of Femara (145 patients). PFS by RESIST was the primary endpoint.

The subgroup analysis showed that the elderly cohort demonstrated similar responses and tolerability to the overall population.

At data cutoff on January 29, 2016, treatment was ongoing in 90 (60 percent) patients receiving ribociclib/ Femara and in 77 (53 percent) patients on placebo/ Femara. Median PFS was not reached with ribociclib Femara versus 18.4 months with placebo/ Femara, HR = 0.608. The ORR in the elderly receiving ribociclib/ Femara versus placebo/ Femara was 37 percent versus 31 percent, respectively.

The median duration of study treatment exposure in elderly patients was 13.1 with ribociclib/ Femara and 12.5 months with placebo/ Femara. In the elderly cohort, 40 percent versus 47 percent of patients receiving ribociclib/ Femara versus placebo/ Femara, respectively, discontinued treatment. The most common reasons for discontinuation were disease progression in 33 (22 percent) versus 51 (35 percent) patients and adverse events (AEs) in 13 (9 percent) versus 5 (3 percent) patients in the ribociclib/ Femara versus placebo/ Femara arms, respectively. One death occurred in the ribociclib combination arm.

“The elderly patients had a slower rate of disease progression in both treatment arms, representing more stabilization of disease,” said Sonke. He also noted in his presentation that over 40 percent of patients diagnosed with breast cancer are aged 65 years or older, and physiologic functioning, comorbidities, or concomitant medications may impact their tolerability of combination regimens.

The rates of AEs in elderly patients were similar to those experienced by the younger patients; AEs that occurred more than 10 percent more frequently with ribociclib/ Femara than with sole Femara included neutropenia (74 percent percent versus 5 percent), leukopenia (31 percent versus 4 percent), fatigue ( 37 percent versus 24 percent), alopecia (33 percent versus 17 percent), diarrhea (41 percent versus 26 percent) and vomiting (35 percent versus 19 percent).

“The rates of dose reduction or interruption due to an AE were similar in both treatment arms in elderly and younger patients, despite a higher proportion of elderly patients with ECOG performance status 1,” Sonke pointed out.

Most AEs could be managed through dose interruption; dose interruptions due to an AE occurred in 13 percent versus 13 percent in the ribociclib/ Femara versus placebo/ Femara arms, respectively, and no dose reductions due to an AE were made in either arm.

The Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for ribociclib in August 2016 and has also accepted a New Drug Application (NDA) and granted priority review for ribociclib as firstline treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer in combination with Femara. The NDA was based in part on results of the MONALEESA-2 trial, which was presented at the European Society for Medical Oncology (ESMO) 2016 Congress and published simultaneously in the New England Journal of Medicine.