Real-World Effectiveness, Safety, and Tolerability of Adjuvant CDK4/6 Inhibitor Therapy

This study evaluates the real-world effectiveness, safety, and tolerability of adjuvant abemaciclib or ribociclib combined with a non-steroidal aromatase inhibitor (NSAI) in high-risk hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer in Western India.

We conducted a retrospective, single-institution study at The Gujarat Cancer and Research Institute (GCRI) in Ahmedabad, India, evaluating high-risk, stage II or III HR+/HER2- early breast cancer patients treated between November 2021 and May 2026. A total of 418 patients were evaluated across three groups: Group 1 received abemaciclib (150 mg twice daily for two years) plus NSAI (letrozole or anastrozole) (n = 138); Group 2 received ribociclib (400 mg daily, three weeks on, one week off for three years) plus NSAI (letrozole or anastrozole) (n = 138); and Group 3 received NSAI (letrozole or anastrozole) alone for ≥ 5 years (n = 142). The primary endpoint was invasive disease-free survival (iDFS), and secondary endpoints included overall survival (OS) and safety.

Baseline characteristics were well-balanced across all three groups, with approximately three-quarters of the patients presenting with advanced stage III disease (77.8%, n=325/418). Adjuvant CDK4/6 inhibitor therapy significantly improved iDFS compared to NSAI alone. Abemaciclib plus NSAI (Group 1) was associated with an approximately 50% relative hazard reduction for an iDFS event compared to NSAI alone (HR 0.50; 95% CI, 0.27-0.91; p = 0.023). Ribociclib plus NSAI (Group 2) demonstrated a 48% relative hazard reduction compared to NSAI alone (HR 0.52; 95% CI, 0.29-0.93; p = 0.027). The estimated two-year iDFS rates were 93.5% (n = 129/138) in Group 1, 88.4% (n = 122/138) in Group 2, and 78.2% (n = 111/142) in Group 3. After applying a Bonferroni correction (α = 0.025), the iDFS benefit remained statistically significant for abemaciclib (p = 0.023), whereas ribociclib (p = 0.027) demonstrated a strong numerical trend that did not meet the adjusted threshold. Overall survival was not estimable due to insufficient events. Adverse events were consistent with established safety profiles: diarrhea was the most frequent adverse event in Group 1 (78.2%, n = 108/138), whereas neutropenia (63.0%, n = 87/138) and arthralgia (71.0%, n = 98/138) were prominent in Group 2. Permanent treatment discontinuation due to adverse events occurred in 13.8% (19/138) of patients in Group 1 and 13% (18/138) in Group 2.

In this retrospective non-randomized study, adding adjuvant abemaciclib or ribociclib to NSAI therapy was associated with two-year iDFS improvements in high-risk HR+/HER2- early breast cancer. However, after Bonferroni correction, the iDFS benefit remained statistically significant for abemaciclib and did not remain statistically significant for ribociclib. The therapies proved highly feasible and manageable in routine clinical practice.