Kisqali (ribociclib)

Real-world data reveal drug- and age-specific toxicity differences. Ribociclib and abemaciclib pose higher risks in older adults compared to palbociclib, supporting the need for personalized treatment and careful monitoring in older patients.

Ribociclib (Ribo) and Abemaciclib (Abe) are new-generation CDK inhibitors approved for use in breast cancer treatment. Some molecular mechanisms were elucidated by revealing the synergistic effect of FA combined with Ribo and/or Abe in both HR positive and HR negative breast cancer and its possible toxicity or protection on normal breast cells. The present findings suggest that FA is a viable candidate for adjuvant or neoadjuvant treatment in combination with Ribo and/or Abe, as an alternative to Letrozole or Fulvestrant, which have been associated with significant adverse effects in clinical settings.

Patients with metastatic HR+HER2- IBC demonstrated a shorter time on treatment suggesting shorter duration of response on CDKI + HT, which is markedly inferior to reported data for non-IBC patients from phase III trials.

P2, N=200, Completed, Melanoma Institute Australia | Active, not recruiting --> Completed | N=1000 --> 200 | Trial completion date: Dec 2028 --> Dec 2025

P=N/A, N=2424, Completed, Novartis Pharmaceuticals | Recruiting --> Completed

At a WTP threshold of $150,000 per evLY, ribociclib demonstrated an approximately 100% probability of being cost-effective relative to palbociclib. Ribociclib improved health outcomes with a minimal relative cost increase and is therefore a highly cost-effective 1 L treatment option vs. palbociclib in patients with HR+/HER2- aBC from the Medicare perspective.

P=N/A, N=376, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P=N/A, N=2766, Not yet recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2032 --> Dec 2032 | Initiation date: Jul 2025 --> Dec 2025 | Trial primary completion date: Jul 2032 --> Dec 2032

At a WTP threshold of $150,000 per evLY, the probability that ribociclib is cost-effective versus abemaciclib, which was 81%. Ribociclib improves health outcomes with a modest impact on costs and is likely to be more cost-effective than abemaciclib for postmenopausal women requiring 1 L treatment of HR+/HER2- aBC from a Medicare perspective.

Tibremciclib shows promise as an additional CDK4/6 inhibitor; however, its global integration requires broader, more diverse clinical trials, robust safety and survival data, and strategies to mitigate toxicity risks. Bridging access gaps will require coordinated efforts across policy, infrastructure, and global partnerships to ensure equitable benefit from emerging therapies.

Early clinical data demonstrated activity of BLU-222, a potent and selective CDK2 inhibitor, both as monotherapy (CCNE1 amplified) and in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer. These findings provide evidence that CDK2i combined with CDK4/6i can address multiple known mechanisms of resistance to CDK4/6i, enhancing antitumor responses in preclinical breast cancer models.

P3, N=1000, Recruiting, Olema Pharmaceuticals, Inc. | Not yet recruiting --> Recruiting