Enfortumab Vedotin (1) – Padcev®

a) Adults with locally advanced or metastatic urothelial carcinoma who have previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor, and who are suitable for chemotherapy

• Hint for a considerable additional benefit
• In the overall assessment, enfortumab vedotin, for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor, a considerable additional benefit compared with chemotherapy as clinically indicated.
• The certainty of evidence for the identified additional benefit is classified as ‘hint’.
• mortality
  • In the EV-301 trial, overall survival was defined as the time from randomisation to death from any cause.
  • For the endpoint of overall survival, a statistically significant advantage was observed in favour of enfortumab vedotin compared with standard chemotherapy.
  • The extent of the prolongation in survival time is assessed as a marked improvement.
  • For this endpoint, there is an effect modification by the characteristic of sex. An advantage in favour of enfortumab vedotin was observed for men. In contrast, no statistically significant difference was observed between the treatment arms for women.
  • The observed effect modification by the characteristic of sex is not considered sufficient to derive separate conclusions regarding additional benefit in the overall assessment.
• Morbidity – Symptoms (EORTC QLQ-C30)
  • The symptoms of patients in the EV-301 study are assessed using the symptom scales of the EORTC QLQ-C30 questionnaire.
  • The pharmaceutical manufacturer provides responder analyses for the proportion of patients with a worsening of ≥ 10 points and ≥ 15 points (scale ranges 0 to 100 respectively). For the benefit assessment, the responder analyses are used with a response threshold of 10 points.
  • The results for the ‘constipation’ symptom scale are not usable. There are uncertainties regarding the use of medicinal products for constipation, and it is unclear to what extent the cases of constipation—some of which were severe—that occurred in the study could have been prevented by prophylaxis.
  • For the endpoints assessed using the EORTC QLQ-C30, there are no statistically significant differences between the treatment arms.
  • However, for the endpoint ‘loss of appetite’, an effect modification by the characteristic of sex was observed. For women, there was a statistically significant advantage in favour of enfortumab vedotin compared with chemotherapy as prescribed by the doctor. In contrast, no statistically significant difference was observed between the treatment arms for men.
  • In the overall analysis of the results, there is no statistically significant difference between the treatment arms with regard to morbidity.
• Morbidity – Health status (EQ-5D VAS)
  • The health status of patients in the EV-301 study is assessed using the EQ-5D VAS.
  • The pharmaceutical manufacturer provides responder analyses for the proportion of patients with a deterioration of ≥ 7 points, ≥ 10 points and ≥ 15 points (scale range 0 to 100). For the benefit assessment, the responder analyses are used with a response threshold of 15 points.
  • No statistically significant difference is observed between the treatment arms.
• Health-related quality of life
  • The quality of life of patients in the EV-301 study is assessed using the functional scales of the EORTC QLQ-C30 questionnaire.
  • The pharmaceutical manufacturer provides responder analyses for the proportion of patients with a deterioration of ≥ 10 points and ≥ 15 points (scale ranges 0 to 100 respectively). For the benefit assessment, the responder analyses are used with a response threshold of 10 points.
  • Overall, a statistically significant advantage in favour of enfortumab vedotin compared with chemotherapy as prescribed by the doctor is observed for each of the functional scales: global health status, physical functioning, role functioning and emotional functioning.
  • However, for the global health status functional scale, there is an effect modification by the characteristic of age. For patients aged ≥ 65 years, there is a statistically significant advantage with enfortumab vedotin compared with chemotherapy as prescribed by the doctor. For patients aged < 65 years, there is no statistically significant difference between the treatment arms.
  • In terms of quality of life, an overall advantage of enfortumab vedotin compared with chemotherapy as prescribed by the doctor can therefore be observed.
• Side effects – Total adverse events (AEs)
  • In the EV-301 trial, AEs occurred in almost all participants in both treatment arms. The results are presented here for supplementary information only.
• Overall assessment
  • Compared with chemotherapy as prescribed by the doctor, enfortumab vedotin leads to a statistically significant prolongation of overall survival. The extent of this prolongation in survival time is assessed as a marked improvement.
  • No statistically significant differences were observed between the treatment arms for the endpoints assessed using the EORTC QLQ-C30.
  • In the functional scales of the EORTC QLQ-C30, a statistically significant advantage in favour of enfortumab vedotin compared with standard chemotherapy was observed for global health status, physical functioning, role functioning and emotional functioning. Overall, an advantage for enfortumab vedotin was observed in terms of quality of life.
  • In the overall analysis of the results on side effects, no relevant difference was observed for enfortumab vedotin compared with standard chemotherapy in terms of the overall rates of serious adverse events (CTCAE grade ≥ 3) and severe adverse events. In detail, there are both advantages and disadvantages for enfortumab vedotin with regard to specific AEs.

b) Adults with locally advanced or metastatic urothelial carcinoma who have previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor and who are not suitable for chemotherapy

• The additional benefit is not proven.
• For adults with locally advanced or metastatic urothelial carcinoma who have previously received platinum-based chemotherapy and a PD-1 or PD-L1inhibitor and who are not suitable for chemotherapy, the pharmaceutical manufacturer has not provided any data for the assessment of additional benefit. Consequently, additional benefit is not proven.

Courtesy translation only, please refer to the German original.