Lorlatinib (2) – Lorviqua®

• Clinical trials
  • The CROWN trial is an open-label, randomised, controlled trial comparing lorlatinib with crizotinib.
  • The ALTA-1L trial is an open-label, randomised, controlled trial in which brigatinib was compared with crizotinib.

Adults with ALK-positive, advanced non-small cell lung cancer (NSCLC) who have not previously been treated with an ALK inhibitor

• For the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC, NSCLC) who have not previously been treated with an ALK inhibitor, additional benefit is not proven.
• mortality
  • In an indirect comparison, no statistically significant difference was observed between lorlatinib and brigatinib for the endpoint of overall survival.
  • An additional benefit in terms of overall survival is therefore not proven.
• Morbidity, health-related quality of life, side effects
  • The endpoints relating to morbidity, health-related quality of life and side effects were assessed in the CROWN and ALTA-1L studies up to 28 and 30 days, respectively, after the last dose of the study medication.
  • Due to this difference in the operationalisation of the follow-up period, patients in the CROWN study were only observed during their (first) course of treatment with crizotinib, whilst in the ALTA-1L study they were observed during (first) course of treatment with crizotinib and also during the subsequent treatment line with brigatinib.
  • Consequently, there is insufficient similarity in the operationalisation of the endpoints relating to morbidity, health-related quality of life and side effects.
  • Consequently, the results cannot be interpreted and the available data are not suitable for an adjusted indirect comparison.
  • Furthermore, there is a high potential for bias in the endpoints relating to morbidity, health-related quality of life and side effects.
  • Thus, the requirements for certainty of results needed to carry out an adjusted indirect comparison for these endpoints are not met.
  • In summary, there are no usable data available for an adjusted indirect comparison for the endpoints of morbidity, health-related quality of life and side effects.
  • An additional benefit for the endpoints of morbidity, health-related quality of life and side effects is therefore not proven in each case.
• Overall assessment / Conclusion
  • An adjusted indirect comparison was submitted for the assessment of the additional benefit of lorlatinib with regard to the endpoints of mortality, morbidity, health-related quality of life and side effects.
  • For the indirect comparison using the bridge comparator crizotinib, the pharmaceutical manufacturer includes the CROWN study on the lorlatinib side and the ALTLA-1L study on the brigatinib side.
  • Despite differences between the CROWN and ALTLA-1L studies in the planned duration of follow-up and the patients’ prior treatment, sufficient similarity for conducting an adjusted indirect comparison using crizotinib as the bridging comparator is not fundamentally called into question.
  • In the indirect comparison, no statistically significant difference was observed between lorlatinib and brigatinib for the endpoint of overall survival. An additional benefit in terms of overall survival is therefore not proven.
  • With regard to the endpoints relating to morbidity, health-related quality of life and side effects, there is insufficient similarity in the operationalisation of these endpoints. Due to the difference in how follow-up was defined, the follow-up period in the CROWN study covers only the (first) course of treatment with crizotinib, whereas the ALTA-1L study includes both the (first) course of treatment with crizotinib and the subsequent treatment line with brigatinib. The available data are therefore not suitable for an adjusted indirect comparison. An additional benefit for the endpoints of morbidity, health-related quality of life and side effects is not proven in each case.
  • Overall, therefore, the additional benefit of lorlatinib over brigatinib is not proven.

Courtesy translation only, please refer to the German original.