Pemigatinib (1) – Pemazyre®

• Clinical trials
  • The FIGHT-202 trial is an open-label, uncontrolled, multicentre Phase II trial designed to investigate the efficacy and safety of pemigatinib in patients with advanced/metastatic or inoperable cholangiocarcinoma who have already received prior treatment.

Adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (fibroblast growth factor receptor 2, FGFR2) fusion or an FGFR2 rearrangement, which has progressed following at least one prior line of systemic therapy

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• Taken as a whole, this results in a hint of a non-quantifiable additional benefit with regard to the validity of the evidence.
• mortality
  • In the FIGHT-202 study, the endpoint of overall survival is defined as the time from the first day of treatment with pemigatinib until death from any cause.
  • As no comparative data are available, it is not possible, on the basis of the results of the FIGHT-202 study, to draw any conclusions regarding the extent of the additional benefit in the mortality category.
• morbidity
  • Progression-free survival is defined in the FIGHT-202 study as the time from the start of treatment until the time of disease progression or death from any cause, whichever occurs first.
  • The PFS endpoint is a composite endpoint comprising endpoints from the ‘mortality’ and ‘morbidity’ categories.
  • The ‘disease progression’ component is based on the assessment of radiological findings. Consequently, morbidity is not primarily assessed on the basis of disease symptoms, but solely on the basis of asymptomatic findings that are not directly relevant to the patient.
  • Taking the above aspects into account, there are differing views within the G-BA regarding the patient relevance of the PFS endpoint.
  • The symptoms of patients in the FIGHT-202 study are assessed using the symptom scales of the EORTC-QLQ-C30 questionnaire.
  • Due to a lack of information on response rates and descriptive analyses for the data cut-off date of 7 April 2020, the results from the data cut-off date of 22 March 2019 are used.
  • As no comparative data are available, a definitive assessment of the effect of pemigatinib on morbidity is not possible.
• Health-related quality of life
  • Health-related quality of life is assessed in the FIGHT-202 study using the functional scales of the EORTC-QLQ-C30 questionnaire.
  • Due to a lack of information on response rates and descriptive analyses for the data cut-off on 7 April 2020, the results from the data cut-off on 22 March 2019 are used.
  • Disease-specific quality of life is assessed in the FIGHT-202 study using the EORTC QLQ-BIL21 only in the USA, the UK, Italy, Germany and Korea.
  • Overall, a definitive assessment of the effect of pemigatinib on quality of life is not possible due to a lack of comparative data.
• Side effects
  • Adverse events were recorded continuously from the signing of the informed consent form until 30 (+ 5) days after discontinuation or completion of treatment with pemigatinib.
  • AE occurred in all patients relevant to the benefit assessment.
  • Serious SAEs were reported. The most common SAEs included those in the system organ classes ‘infections and parasitic diseases’ and ‘gastrointestinal disorders’.
  • Severe AEs occurred in 66.7% of study participants. The most frequently reported severe AEs were those in the system organ classes ‘Gastrointestinal disorders’ and ‘Metabolic and nutritional disorders’.
  • Treatment with pemigatinib was discontinued by 7 of the 108 patients (6.5%) due to AEs.
  • The majority of patients relevant to the benefit assessment reported the occurrence of AEs of particular clinical interest (84.3%). AEs were most frequently reported in the ‘hyperphosphataemia’ and ‘nail toxicity’ groups.
  • In summary, due to the lack of a control population, it is not possible to carry out a comparative analysis of the incidence of safety events.
• Overall assessment / Conclusion
  • For the assessment of the additional benefit of pemigatinib in the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (fibroblast growth factor receptor 2, FGFR2) fusion or an FGFR2 rearrangement, whose disease has progressed following at least one prior line of systemic therapy, results from the uncontrolled FIGHT study are available for the endpoint categories of mortality, morbidity, quality of life and side effects.
  • A comparative assessment of the study results is not possible due to the uncontrolled design of the FIGHT-202 study.
  • The indirect comparison of overall survival presented by the pharmaceutical manufacturer in the dossier, based on data from the publication by Jain et al., 2018, is not taken into account. Limitations include methodological weaknesses arising from the backdating of the start of the observation period, as well as missing information or missing tables in the publication by Jain et al., meaning that the comparability of the two study populations cannot be assessed.
  • Consequently, it is not possible to quantify the additional benefit on the basis of the data presented.
  • Overall, for pemigatinib in the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (fibroblast growth factor receptor 2, FGFR2) fusion or an FGFR2 rearrangement, which has progressed following at least one prior line of systemic therapy, because the scientific evidence does not permit quantification of the non-quantifiable additional benefit.

Courtesy translation only, please refer to the German original.