Palbociclib (3) – Ibrance®

• Clinical trials
  • To demonstrate the additional benefit of palbociclib in combination with letrozole compared with letrozole alone, the pharmaceutical manufacturer has submitted the results of the randomised, double-blind, controlled Phase III PALOMA-2 trial.
  • The PALOMA-4 trial is a double-blind, randomised and controlled Phase III trial comparing palbociclib in combination with letrozole with letrozole alone.

a1) postmenopausal patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer receiving first-line treatment

• The additional benefit is not proven.
• As the pharmaceutical manufacturer submitted only incomplete analyses regarding quality of life and morbidity from the PALOMA-2 trial, no evaluable data on the effects on quality of life and morbidity are available for assessment.
• The G-BA notes that, in accordance with Chapter 5 Chapter, Section 18(1) of the G-BA’s Rules of Procedure (VerfO), the presentation of the documents in the dossier deviates from the requirements set out in Chapter 5, Section 9 of the G-BA’s Rules of Procedure to such an extent that it precludes a proper assessment of the additional benefit.
• Consequently, the G-BA finds, in accordance with Chapter 5, Section 18(1), fourth sentence, of the G-BA’s Rules of Procedure, that the additional benefit is not proven.
• mortality
  • The results of the third and most recent data collection, dated 15 November 2021, are relevant to this benefit assessment.
• morbidity
  • In its dossier assessment, the IQWiG noted that the pharmaceutical manufacturer had not, in the dossier for the current third data cut-off of the PALOMA-2 study dated 15 November2021, the pharmaceutical company had not provided a complete analysis of the results for all endpoints relevant to the benefit assessment.
  • Specifically, the pharmaceutical manufacturer presents, from the PALOMA-2 study on health-related quality of life and morbidity, only analyses relating to the second data cut-off date of 31 May 2017, but not to the current third data cut-off date of 15 November 2021.
  • In its dossier assessment, the IQWiG states that the assumption that symptoms and quality of life would change less over the course of the follow-up is, in itself, inappropriate.
  • Furthermore, the pharmaceutical manufacturer’s approach does not comply with the G-BA’s time-limit requirements, according to which, for the renewed benefit assessment following the expiry of the deadline, the final study results of the PALOMA-2 study for all endpoints relevant to the benefit assessment should be presented in the dossier.
  • The IQWiG notes that the analyses of health-related quality of life and morbidity from the PALOMA-2 study submitted by the pharmaceutical manufacturer in the dossier are therefore not usable for the benefit assessment, and that the results submitted for the PALOMA-2 are incomplete in terms of content.
  • Although the dossier contains results for the endpoints of health-related quality of life and morbidity from the PALOMA-4 study, based on the most recent data cut-off for that study, these are not meaningful when considered in isolation.
  • Accordingly, according to the IQWiG, there are no usable data available on health-related quality of life and morbidity.
• Health-related quality of life
  • In its dossier assessment, the IQWiG noted that the pharmaceutical manufacturer had not, in the dossier for the current third data cut-off of the PALOMA-2 study dated 15 November2021, the pharmaceutical company had not provided a complete analysis of the results for all endpoints relevant to the benefit assessment.
  • Specifically, the pharmaceutical manufacturer presents, from the PALOMA-2 study on health-related quality of life and morbidity, only analyses relating to the second data cut-off date of 31 May 2017, but not to the current third data cut-off date of 15 November 2021.
  • In its dossier assessment, the IQWiG states that the assumption that symptoms and quality of life would change less over the course of the follow-up is, in itself, inappropriate.
  • Furthermore, in the PALOMA-2 study specifically, quality of life was in some cases also assessed beyond the end of treatment.
  • Furthermore, the pharmaceutical manufacturer’s approach does not comply with the G-BA’s time-limit requirements, according to which, for the renewed benefit assessment following the expiry of the time limit, the final study results of the PALOMA-2 study for all endpoints relevant to the benefit assessment should be submitted in the dossier.
  • The IQWiG notes that the analyses of health-related quality of life and morbidity from the PALOMA-2 study submitted by the pharmaceutical manufacturer in the dossier are therefore not usable for the benefit assessment, and that the results submitted for the PALOMA-2 are incomplete in terms of content.
  • Although the dossier contains results for the endpoints of health-related quality of life and morbidity from the PALOMA-4 study, based on the most recent data cut-off for that study, these are not meaningful when considered in isolation.
  • Accordingly, according to the IQWiG, there are no usable data available on health-related quality of life and morbidity.
• Side effects
  • In its overall assessment, the IQWiG states that only adverse effects have been reported for palbociclib + letrozole compared with letrozole alone.
  • In its overall assessment of additional benefit, the IQWiG concludes that there is proof of less benefit from palbociclib plus letrozole compared with letrozole alone.
• Conclusion
  • As the pharmaceutical manufacturer submitted only incomplete analyses of the quality of life and morbidity data collected in the PALOMA-2 study, no evaluable data on the effects on quality of life and morbidity are available for the assessment.
  • Meaningful data on quality of life and morbidity are generally considered to be of great importance in benefit assessments, particularly in advanced stages of cancer.
  • In the present assessment, it is in particular not possible to assess the extent to which the increase in significant severe side effects (CTCAE ≥ Grade 3) – a high proportion of which were identified via laboratory findings – corresponds to changes in quality of life compared with the control group.
  • For these reasons, in the present case, the data submitted for the benefit assessment is considered to be so seriously incomplete that, overall, it is not possible to carry out a sufficiently reliable and appropriate assessment.

Courtesy translation only, please refer to the German original.