Ceritinib (2) – Zykadia®

1) Patients who are eligible for treatment with docetaxel or pemetrexed

• mortality
  • overall survival
  • For the endpoint of overall survival, there was no statistically significant difference between the treatment groups in the trial (hazard ratio: 1.00 [0.67; 1.49], p-value = 0.496). An additional benefit of ceritinib over chemotherapy with docetaxel or pemetrexed is not proven for overall survival.
  • The median survival time in the treatment groups was 18.1 months (ceritinib) and 20.1 months (docetaxel or pemetrexed).
  • The assessment takes into account that, at the time of the analysis, 64.7% of patients in the chemotherapy group had switched to follow-up treatment with ceritinib (‘cross-over’), which means that the overall survival result is subject to potentially significant bias.
• Morbidity – Progression-free survival
  • Progression-free survival (PFS) was statistically significantly longer in the ceritinib treatment group: a median of 5.4 months (ceritinib) versus 1.6 months (chemotherapy); hazard ratio: 0.49 [0.36; 0.67], p-value < 0.001.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
  • The morbidity component was not assessed on the basis of symptoms, but exclusively by means of imaging procedures.
• Health-related quality of life
  • Health-related quality of life was assessed in this study using the functional scales and the scale for measuring overall health status from the cancer-specific EORTC QLQ-C30 questionnaire.
  • For the endpoints of physical functioning, role functioning and social functioning, a statistically significant advantage was observed for ceritinib compared with docetaxel or pemetrexed.
  • For the other endpoints – overall health status, emotional functioning and cognitive functioning – no statistically significant difference was observed.
  • Overall, an improvement in health-related quality of life was observed with treatment using ceritinib compared with chemotherapy using docetaxel or pemetrexed.
• Side effects
  • Almost every patient in this study experienced adverse events at least once, including those treated with ceritinib as well as those treated with docetaxel or pemetrexed.
  • Serious adverse events (SAEs) occurred in 42.6% of patients in the ceritinib treatment group and in 31.9% of patients in the chemotherapy treatment group.
  • The vast majority of patients in both treatment groups were affected by adverse events classified as ‘severe adverse events’ (CTCAE Grade 3 or 4): 77.4% and 63.7%, respectively.
  • Analysis of the time to first occurrence showed no statistically significant difference.
  • Furthermore, no statistically significant difference was observed in therapy discontinuations due to adverse events.
  • For the endpoints ‘General disorders and administration site conditions’, ‘Nervous system disorders’, ‘Respiratory, thoracic and mediastinal disorders’, ‘Blood and lymphatic system disorders’ (CTCAE Grade 3 or 4), musculoskeletal, connective tissue and bone disorders (CTCAE Grade 3 or 4) and psychiatric disorders, ceritinib demonstrated statistically significant advantages over docetaxel or pemetrexed in each case.
  • For the endpoint of gastrointestinal disorders, there is a statistically significant disadvantage of ceritinib compared with docetaxel or pemetrexed.
  • Overall, the results for the selected specific adverse events show partly positive and partly negative effects for ceritinib, with the positive effects clearly predominating, particularly for those specific adverse events showing a statistically significant difference in events of higher severity (CTCAE Grade 3 or 4).
• Overall assessment
  • Data are available from the ASCT study for the assessment of the additional benefit of ceritinib in the treatment of advanced, anaplastic lymphoma kinase (ALK)-positive, non-small cell lung cancer (NSCLC) following prior treatment with crizotinib, the ASCEND-5 study provides results on mortality (overall survival), morbidity, health-related quality of life and side effects compared with the appropriate comparator therapy (docetaxel or pemetrexed).
  • An additional benefit for treatment with ceritinib is not proven in terms of overall survival. The assessment takes into account that, at the time of the analysis, 64.7% of patients in the chemotherapy treatment group had switched to follow-up treatment with ceritinib (‘cross-over’), meaning that the overall survival result is subject to potentially significant bias.
  • The results regarding symptoms show a significant overall improvement with ceritinib, particularly for symptoms that are characteristic of advanced lung cancer and significant for patients.
  • Furthermore, a comparison of the treatments’ effects on health-related quality of life reveals an improvement with ceritinib across several dimensions of health-related quality of life.
  • With regard to side effects, there is neither an advantage nor a disadvantage for ceritinib in terms of the endpoints of serious adverse events (SAEs), severe adverse events (CTCAE Grade 3 or 4) and therapy discontinuation due to adverse events. For the specific adverse events considered, ceritinib has a predominantly positive effect.
  • Overall, ceritinib is found to provide additional benefit in this therapeutic indication compared with chemotherapy using docetaxel or pemetrexed. The extent of the additional benefit is classified as ‘considerable’, taking into account the very advanced stage of the disease and the advanced stage of treatment, in which patients have already received ALCL-specific therapy.

2) Patients for whom treatment with docetaxel or pemetrexed is not an option

• For patients for whom treatment with docetaxel or pemetrexed is not an option, an additional benefit is not proven.
• No data were submitted for the group of patients for whom treatment with docetaxel or pemetrexed is not an option to assess the additional benefit of ceritinib compared with the appropriate comparator therapy (best supportive care).

Courtesy translation only, please refer to the German original.