Subgroup findings boost ribociclib-letrozole potential in Asians with HR+, HER2– advanced breast cancer

In a subgroup analysis of the phase IIIb CompLEEment-1 trial, ribociclib plus letrozole showed a manageable safety profile in Asian patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) advanced breast cancer (ABC).

“[Our findings show that] the safety profile of ribociclib plus letrozole was manageable, with few patients discontinuing treatment due to adverse events (AEs),” said Dr Sanjoy Chatterjee from the Tata Medical Center, Kolkata, India, who presented the findings at ESMO Asia 2020.

CompLEEment-1 evaluated the efficacy and safety of ribociclib plus letrozole in a large, diverse cohort of women of any premenopausal status, as well as men, with HR+, HER2– ABC (n=3,246) using a broad inclusion criteria*. Participants were given a daily dose of ribociclib 600 mg (3 weeks on, 1 week off) and letrozole 2.5 mg (continuous). Concomitant goserelin or leuprolide were given once a month. [J Clin Oncol 2019;37:1041]

The current analysis looked into data of the Asian** patients (n=197; 1.5 percent male, median age 52 years, 34 percent premenopausal women) from the core CompLEEment-1 cohort. [ESMO Asia 2020, abstract 48MO]

Compared with the core population, the Asian subgroup had a lower rate of AEs leading to discontinuation (10 percent vs 16 percent). Despite a higher incidence of all-grade pyrexia in the Asian subgroup vs the overall cohort (24.4 percent vs 12.8 percent), the rate of nausea was noticeably low (22.8 percent vs 35.9 percent).

There were slight differences between the overall population and the Asian subgroup in terms of AEs of special interest, noted Chatterjee. Compared with the overall cohort, the Asian subgroup had a lower rate of grade ≥3 neutropenia (49.2 percent vs 57.2 percent) but higher incidence of grade ≥3 QT interval prolongation (4.1 percent vs 1.0 percent).

Median time to progression was, however, shorter in the Asian subset vs the overall population (20.3 vs 27.1 months). “This is mainly explained by the … higher proportion of patients with disease characteristics generally associated with poorer prognosis [in the Asian subset vs the overall cohort],” explained Chatterjee.

Compared with the overall population, the Asian subset had more patients with ECOG PS*** 1–2 (64.5 percent vs 39.2 percent), visceral metastases (65.5 percent vs 61.4 percent), ≥3 sites of metastatic disease (51.8 percent vs 43.3 percent), and had relapsed within 2 years of adjuvant therapy (18.3 percent vs 11.8 percent).

Among patients with measurable disease, overall response rate (ORR) and clinical benefit rate (CBR) were similar between the Asian subset and overall cohort (44.9 percent vs 43.4 percent [ORR] and 68.6 percent vs 69.1 percent [CBR]).

Taken together, the findings support the clinical potential of ribociclib plus letrozole for HR+, HER2– ABC in the often underrepresented Asian setting, noted Chatterjee. These results also reinforce findings from previous phase III trials demonstrating an OS benefit when ribociclib is given alongside endocrine therapy in women with HR+, HER2– ABC. [N Engl J Med 2019;381:307-316; N Engl J Med 2020;382:514-524]