Ribociclib (1) – Kisqali®

• Clinical trials
  • The pharmaceutical manufacturer has submitted the results of the double-blind, randomised, controlled MONALEESA-2 trial to demonstrate the additional benefit of ribociclib; this trial directly compares ribociclib in combination with letrozole against placebo in combination with letrozole.

postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer as initial endocrine-based therapy

• For postmenopausal women with hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer, additional benefit from ribociclib in combination with letrozole as initial endocrine-based therapy is not proven compared with letrozole monotherapy.
• mortality
  • Overall survival was defined as the time from the date of randomisation to the date of death, regardless of the underlying cause of death.
  • For overall survival, the MONALEESA-2 trial showed no statistically significant difference between the treatment arms (HR: 0.75 [0.52; 1.08]; p = 0.118).
  • Conclusion: Based on the available, as yet immature data, there is no additional benefit from the combination of ribociclib with letrozole for the endpoint category of mortality.
• morbidity
  • Progression-free survival (PFS)
  • A statistically significant difference was observed between the treatment groups for progression-free survival (HR: 0.57 [0.46; 0.70]; p < 0.001). The median progression-free survival was prolonged by 9.3 months with ribociclib in combination with letrozole compared with letrozole monotherapy.
  • The results for the endpoint of progression-free survival are therefore not included in this review.
  • Time to first subsequent chemotherapy
  • The results for the endpoint ‘time to first subsequent chemotherapy’ are therefore not included in this assessment.
  • Symptoms of the disease
  • No statistically significant difference between the treatment arms was observed on any symptom scale.
  • health status
  • For the health status endpoint, there was no statistically significant difference between the treatment arms, whether using an MID of 7 or an MID of 10.
  • Conclusion: Based on the available data, the combination of ribociclib with letrozole does not provide any additional benefit for the endpoint category of morbidity.
• Health-related quality of life
  • No statistically significant difference was observed between the treatment arms on any functional scale.
  • Conclusion: Based on the available data, the combination of ribociclib with letrozole does not provide any additional benefit for the health-related quality of life endpoint category.
• Side effects
  • Serious adverse events (SAEs)
  • For the SAE endpoint, there was a statistically significant effect to the detriment of ribociclib plus letrozole compared with letrozole alone (HR: 1.65 [1.17; 2.34]; p = 0.004).
  • Severe AEs (CTCAE Grade 3 or 4)
  • For severe AEs (CTCAE Grade 3 or 4), there was also a statistically significant effect to the detriment of ribociclib plus letrozole compared with letrozole monotherapy (HR: 4.21 [3.40; 5.21]; p < 0.001).
  • Discontinuation due to AEs
  • For this endpoint, there was a statistically significant effect to the detriment of ribociclib plus letrozole compared with letrozole monotherapy (RR: 4.26 [2.37; 7.63]; p < 0.001).
  • Specific AEs
  • In particular, for the SOC ‘Blood and lymphatic system disorders’ (severe AEs) and the SOC ‘Investigations’ (severe AEs), there were significant disadvantages for the combination of ribociclib and letrozole compared with letrozole monotherapy (HR: 26.89 [13.76; 52.56]; p < 0.001 and HR: 5.47 [3.61; 8.29]; p < 0.001).
  • Conclusion: Based on the available data, a number of significant disadvantages associated with the combination of ribociclib and letrozole can be identified in the ‘side effects’ endpoint category.
• Overall assessment
  • For the assessment of the extent of the additional benefit of ribociclib in combination with letrozole, results from the MONALEESA-2 study are available in comparison with letrozole for the endpoint categories of mortality (overall survival), morbidity, health-related quality of life and side effects.
  • In the mortality endpoint category, the preliminary data for the overall survival endpoint do not allow for a definitive assessment of the effects on overall survival.
  • For endpoints in the morbidity and health-related quality of life categories, there is also no statistically significant difference between ribociclib in combination with letrozole and letrozole monotherapy.
  • With regard to side effects, serious adverse events (SAEs), severe adverse events (CTCAE grade 3 or 4) were observed in terms of the endpoints and discontinuation due to AEs, significant disadvantages were identified for ribociclib in combination with letrozole compared with letrozole monotherapy, particularly with regard to the pronounced myelosuppression and liver toxicity observed with ribociclib.
  • In its cost-benefit analysis, the G-BA concludes that there is no demonstrated added benefit for ribociclib in combination with letrozole in the treatment of postmenopausal patients with hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer does not have any additional benefit compared with letrozole monotherapy.

Courtesy translation only, please refer to the German original.