Cabozantinib (Cabometyx, 5) – Cabometyx®

• Clinical trials
  • These studies are randomised, open-label, controlled, multicentre Phase III trials.

a) Adult patients with previously untreated, advanced renal cell carcinoma with a favourable risk profile (IMDC score 0)

• An additional benefit is not proven.

b) Adult patients with untreated, advanced renal cell carcinoma with an intermediate (IMDC score 1–2) or unfavourable risk profile (IMDC score ≥ 3)

• An additional benefit is not proven.
• Overall, therefore, for patient population b), there are neither positive nor negative effects of cabozantinib in combination with nivolumab compared with pembrolizumab in combination with axitinib. An additional benefit of cabozantinib in combination with nivolumab compared with pembrolizumab in combination with axitinib is not proven.
• mortality
  • For the endpoint of overall survival, the adjusted indirect comparison shows no statistically significant difference between the treatment groups.
  • With regard to overall survival, therefore, the additional benefit of cabozantinib in combination with nivolumab is not proven.
• Morbidity – FKSI-DRS and EQ-5D VAS
  • Consequently, no data are available for the indirect comparison, as only the data from the CheckMate 9ER trial are usable.
  • Furthermore, both the CheckMate 9ER study and the KEYNOTE 426 study are open-label studies. This would result in a high potential for bias in the results of the patient-reported endpoints in both studies. Consequently, the requirements regarding the reliability of the results for conducting an indirect comparison would also not be met.
  • Overall, therefore, no usable data are available for the patient-reported endpoints relating to symptoms.
• quality of life
  • No data on health-related quality of life were collected in the CheckMate 9ER trial. An adjusted indirect comparison is therefore not possible.
• Side effects – serious adverse events (SAEs) and severe AEs (CTCAE grade ≥ 3)
  • For the endpoints SAE and severe AEs (CTCAE grade ≥ 3), the adjusted indirect comparison shows no statistically significant differences between cabozantinib in combination with nivolumab and pembrolizumab in combination with axitinib.
• Side effects – Therapy discontinuation due to AEs
  • The potential for bias in the results for the endpoint ‘therapy discontinuation due to AEs’ is considered high due to the open-label design of the CheckMate 9ER and KEYNOTE 426 trials. The results for this endpoint in the context of an indirect comparison are therefore considered unusable.
• Side effects – Immune-mediated SAEs and immune-mediated severe AEs
  • The CheckMate 9ER study provides results only for individual immune-mediated adverse events, but no overall rates for immune-mediated serious adverse events or immune-mediated severe adverse events. No results are available from the KEYNOTE 426 trial corresponding to the populations relevant to the questions addressed in this benefit assessment. Consequently, no usable data are available for an indirect comparison.
• Overall assessment
  • For the assessment of the additional benefit of cabozantinib in combination with nivolumab in the first-line treatment of advanced renal cell carcinoma in adults, the following results are available for the patient group with an intermediate or unfavourable risk profile (patient population b)) results on overall survival and side effects compared with the appropriate comparator therapy, pembrolizumab in combination with axitinib.
  • The present assessment is based on an adjusted indirect comparison, using the procedure described by Bucher et al., of the CheckMate 9ER (cabozantinib in combination with nivolumab vs. sunitinib) and KEYNOTE 426 (pembrolizumab in combination with axitinib versus sunitinib). Cabozantinib in combination with nivolumab was compared with pembrolizumab in combination with axitinib via the bridge comparator sunitinib.
  • For the endpoint of overall survival, the adjusted indirect comparison shows no statistically significant difference between the treatment groups. With regard to overall survival, therefore, the additional benefit of cabozantinib in combination with nivolumab is not proven.
  • No usable data are available for an adjusted indirect comparison of the patient-reported endpoints relating to symptoms and health status.
  • No data on health-related quality of life were collected in the CheckMate 9ER trial. An adjusted indirect comparison is therefore not possible.
  • With regard to side effects, the adjusted indirect comparison shows no statistically significant differences for the endpoints of serious adverse events (SAE) and severe adverse events (CTCAE grade ≥ 3). No usable data are available for further endpoints in the side effect category.
  • Overall, therefore, for patient population b), there are neither positive nor negative effects of cabozantinib in combination with nivolumab compared with pembrolizumab in combination with axitinib. An additional benefit of cabozantinib in combination with nivolumab over pembrolizumab in combination with axitinib is not proven.

Courtesy translation only, please refer to the German original.