Alectinib (3) – Alecensa®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer submitted the results from the ongoing, open-label, randomised, controlled Phase III ALINA trial.

a) Adults with ALK-positive NSCLC at high risk of recurrence, receiving adjuvant treatment following complete tumour resection, who are suitable for adjuvant platinum-based chemotherapy

• The findings indicate that alectinib offers a major additional benefit compared with platinum-based chemotherapy.
• The certainty of the evidence is therefore classified as ‘hint’.
• mortality
  • For the endpoint of overall survival, there is no statistically significant difference between the treatment arms.
  • At the time of the data cut-off (pre-specified analysis for disease-free survival), the total number of events was very minor.
• Morbidity – Recurrences
  • These endpoints are characterised by the recurrence rate and disease-free survival, and include the events of local recurrence, regional recurrence, distant recurrence, new primary NSCLC and death from any cause.
  • The recurrence rate is defined as the proportion of patients who, following complete tumour resection, experience a recurrence, develop a new primary NSCLC or die by the current data cut-off date.
  • Disease-free survival is defined as the time from randomisation to the occurrence of a recurrence, a new primary NSCLC or death, whichever occurs first.
  • For both endpoints (recurrence rates and disease-free survival), there is a statistically significant advantage in favour of alectinib, based on the investigators’ assessment, with an extent that is considered a very large improvement.
  • It should be noted that the present analyses are based on a median follow-up period of approximately 28 months (intervention arm 30.0 months, control arm 23.5 months). A median follow-up period of approximately 28 months is not considered sufficient in the present treatment context to adequately reflect the high-risk period for the occurrence of a recurrence.
• Quality of life – SF-36v2 – physical and mental health summary scores
  • Health-related quality of life was assessed using the SF-36v2.
  • In the analysis of deterioration at week 12, no statistically significant difference was observed between the treatment arms for the PCS. In contrast, a statistically significant advantage was observed for the MCS, favouring alectinib over platinum-based chemotherapy.
  • It should be noted that the available analyses of health-related quality of life only provide insights into a single early time point during treatment.
• Side effects
  • Side effects were recorded in both treatment groups up to 28 days after the last dose of the study medication.
  • Due to the differing observation periods in the treatment groups, the median observation period for the ‘side effects’ endpoint category differs significantly between the two treatment groups (24.8 months in the intervention arm versus 3.7 months in the control arm). Consequently, the hazard ratio reflects only the first 4 months or so.
  • For the endpoints SAE and severe AEs (CTCAE grade ≥ 3), a statistically significant advantage was observed in favour of alectinib compared with platinum-based chemotherapy.
  • For the endpoint of therapy discontinuations due to AEs (all active ingredients in the comparator arm), there is a statistically significant advantage for alectinib compared with platinum-based chemotherapy.
  • For the specific adverse events (AEs) of malaise (AE), reduced appetite (AE) and haematopoietic cytopenia (severe AE), a statistically significant advantage was observed in favour of alectinib compared with platinum-based chemotherapy.
  • For the specific AEs of hepatotoxicity (severe AE) and elevated blood creatine phosphokinase (severe AE), a statistically significant disadvantage was observed in each case compared with platinum-based chemotherapy.
  • For the endpoints myalgia (severe AE) and ILD/pneumonitis (SAE), no statistically significant difference was observed between the treatment arms.
  • Overall, alectinib shows advantages in terms of serious AEs (SAEs), severe AEs (CTCAE grade ≥ 3) and therapy discontinuations due to AEs. In detail, both advantages and disadvantages of treatment with alectinib compared with platinum-based chemotherapy can be identified for the specific AEs.
  • No conclusions can be drawn from the data regarding side effects occurring in the longer term.
• Overall assessment
  • For the endpoint of overall survival, there is no statistically significant difference between the treatment arms.
  • Preventing recurrence is an essential treatment objective in this curative treatment setting. For the two endpoints of recurrence rate and disease-free survival, a statistically significant advantage was observed in favour of alectinib, which is regarded as a very substantial improvement.
  • No statistically significant difference was observed between the treatment arms with regard to health status (assessed using the EQ-5D VAS).
  • Conclusions regarding longer-term effects on health-related quality of life cannot be drawn on the basis of the data. In the analyses of deterioration at week 12 (assessed using the SF-36), there was a statistically significant advantage for alectinib with respect to the mental health summary score (MCS). For the physical composite score (PCS), there is no statistically significant difference between the treatment arms.
  • Due to the short observation period in the comparator arm, the event-time analyses for side effects allow only comparative conclusions to be drawn for the period of approximately the first 4 months of treatment. There are statistically significant advantages for alectinib in terms of serious AEs (SAEs), severe AEs (CTCAE grade ≥ 3) and therapy discontinuations due to AEs. In detail, both advantages and disadvantages of treatment with alectinib compared with platinum-based chemotherapy can be identified for specific AEs.
  • Overall, alectinib shows advantages in terms of recurrence-related endpoints and in relation to serious AEs, severe AEs (CTCAE grade ≥ 3) and therapy discontinuations due to AEs.
  • In the overall assessment, a major additional benefit is identified for alectinib compared with platinum-based chemotherapy.

b) Adults with ALK-positive NSCLC at high risk of recurrence, for adjuvant treatment following complete tumour resection after prior adjuvant platinum-based chemotherapy, or who are unsuitable for such treatment

• The additional benefit is not proven
• No data are available to enable an assessment of the additional benefit.

Courtesy translation only, please refer to the German original.