Nivolumab (17) – Opdivo®

• Clinical trials
  • The pharmaceutical manufacturer submitted data for the benefit assessment from the open-label, randomised, controlled Phase IIICA209-743, in which nivolumab in combination with ipilimumab was compared with pemetrexed in combination with cisplatin or pemetrexed in combination with carboplatin.

a) Adults with unresectable malignant pleural mesothelioma and epithelioid tumour histology; first-line treatment

• The additional benefit is not proven.
• mortality
  • For the endpoint of overall survival, there is no statistically significant difference between the treatment arms in the group of patients with epithelioid tumour histology.
  • An additional benefit for this patient group in terms of overall survival is therefore not proven.
• Morbidity – Symptoms (LCSS-Meso ASBI)
  • In the morbidity endpoint category, a statistically significant difference in favour of nivolumab in combination with ipilimumab was observed with regard to symptoms (LCSS-Meso ASBI).
• Morbidity – Health status (EQ-5D Visual Analogue Scale)
  • For patients with epithelioid tumour histology, there is no statistically significant difference between the treatment arms.
• Health-related quality of life
  • No data on health-related quality of life were collected in the CA209-743 study.
  • The pharmaceutical manufacturer classifies the remaining three items of the LCSS-Meso (symptom burden, activity impairment and general health-related quality of life) as relating to health-related quality of life. However, these items are not suitable for capturing the complex construct of health-related quality of life.
• Side effects – Serious adverse events (SAEs)
  • For patients with epithelioid tumour histology, there is a statistically significant difference to the clear disadvantage of nivolumab in combination with ipilimumab for the SAE endpoint.
• Side effects – severe adverse events (CTCAE grade ≥ 3)
  • There were no statistically significant differences for the endpoints of severe AEs (CTCAE grade ≥ 3) and discontinuation due to AEs (discontinuation of at least one treatment component).
• Side effects – Therapy discontinuations due to adverse events
  • There were no statistically significant differences in the endpoints of severe AEs (CTCAE grade ≥ 3) and discontinuation due to AEs (discontinuation of at least one treatment component).
• Overall assessment
  • On balance, therefore, the positive effect of symptom improvement is offset by a clear disadvantage in terms of SAE.
  • In its decision-making process, the G-BA concludes that, for nivolumab in combination with ipilimumab as first-line treatment for non--resectable malignant pleural mesothelioma in adults with epithelioid tumour histology, an additional benefit is not proven compared with the appropriate comparator therapy.

b) Adults with unresectable malignant pleural mesothelioma and non-epithelioid tumour histology; first-line treatment

• Indication of a considerable additional benefit.
• mortality
  • For patients with non-epithelioid tumour histology, there is a statistically significant advantage in favour of nivolumab in combination with ipilimumab.
  • For these patients, there is an extension of survival time, the extent of which is assessed as a significant improvement.
• Morbidity – health status (EQ-5D Visual Analogue Scale)
  • For patients with non-epithelioid tumour histology, there is a statistically significant advantage in favour of nivolumab in combination with ipilimumab.
• Health-related quality of life
  • No data on health-related quality of life were collected in the CA209-743 study.
  • The pharmaceutical manufacturer classifies the remaining three items of the LCSS-Meso (symptom burden, activity impairment and general health-related quality of life) as relating to health-related quality of life. However, these items are not suitable for capturing the complex construct of health-related quality of life.
• Side effects – Serious adverse events (SAEs)
  • For patients with non-epithelioid tumour histology, there is no statistically significant difference between the treatment arms.
• Overall assessment
  • On balance, therefore, the positive effects in terms of overall survival, symptoms and health status are not offset by any disadvantages.
  • Consequently, the G-BA concludes that nivolumab in combination with ipilimumab, as first-line therapy for unresectable malignant pleural mesothelioma in adults with non-epithelioid tumour histology, offers a considerable additional benefit compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.