Mirvetuximab-Soravtansin (1) – Elahere®

Adult female patients with FR-α-positive, platinum-resistant, high-grade serous epithelial carcinoma of the ovaries or fallopian tubes, or with primary peritoneal carcinoma, who have already received 1 to 3 previous courses of treatment

• Overall, the G-BA has established that mirvetuximab soravtansin offers a considerable additional benefit for patients with FR-α-positive, platinum-resistant, high overall survival-grade serous epithelial carcinoma of the ovaries, fallopian tubes or primary peritoneal carcinoma, who have already received 1 to 3 previous lines of treatment.
• The strength of the evidence for the established additional benefit is classified overall as an indication.
• mortality
  • In the MIRASOL and FORWARD 1 studies, overall survival is defined as the time from randomisation to death from any cause.
  • For the endpoint of overall survival, the MIRASOL study and the meta-analysis show a statistically significant advantage in favour of mirvetuximab soravtansin.
  • The extent of the prolongation achieved in overall survival is assessed as a relevant improvement.
• Morbidity – Progression-free survival (PFS)
  • Progression-free survival (PFS) was defined in the MIRASOL and FORWARD 1 studies as the time from randomisation to the date of radiological disease progression or to death from any cause, whichever occurred first.
  • For the PFS endpoint, both the MIRASOL study and the meta-analysis show a statistically significant advantage in favour of mirvetuximab soravtansin.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
  • Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint to patients. The overall conclusion regarding additional benefit remains unaffected.
• Morbidity – Symptoms
  • Response rates are already below 70% from week 8/9 onwards, and thus for the first assessment after baseline, for all instruments.
• Health-related quality of life – EORTC QLQ-C30 and EORTC QLQ-OV28
  • The response rates are < 70 % and are therefore not suitable for the benefit assessment (detailed description in the section on symptoms).
• Side effects – serious adverse events (SAEs), severe adverse events (CTCAE grade 3 or 4) and therapy discontinuations due to adverse events
  • For the endpoints SAE, severe AEs and therapy discontinuations due to AEs, statistically significant advantages were observed in favour of mirvetuximab soravtansin.
  • Overall, within the ‘side effects’ endpoint category, there is a clear advantage for mirvetuximab soravtansin compared with treatment as medically indicated, comprising paclitaxel, pegylated liposomal doxorubicin and topotecan.
• Side effects – Specific adverse events
  • In detail, for severe AEs (with an incidence of ≥ 5% in at least one study arm), statistically significant advantages were observed in the intervention arm for “Blood and lymphatic system disorders, SOC” (MIRASOL and FORWARD 1 studies and meta-analysis), ‘General disorders and administration site conditions, SOC’ (MIRASOL and FORWARD 1 studies and meta-analysis), ‘Investigations, SOC’ (MIRASOL study and meta-analysis), ‘Anaemia, PT’ (MIRASOL study and meta-analysis), ‘Neutropenia, PT’ (MIRASOL study and meta-analysis), “Thrombocytopenia, PT” (MIRASOL study) and “Fatigue, PT” (MIRASOL study and meta-analysis).
  • For the SAE (with an incidence of ≥ 5% in at least one study arm), a statistically significant advantage was observed in the intervention arm for ‘Small bowel obstruction, PT’ (MIRASOL study and meta-analysis) and ‘gastrointestinal disorders, SOC’ (meta-analysis).
  • For AEs of particular interest, statistically significant disadvantages were observed in the intervention arm for ‘pneumonitis, AE regardless of severity’ (MIRASOL study) and ‘peripheral neuropathy, AE regardless of severity’ (MIRASOL study and meta-analysis), as well as in the following PTs for ‘Eye diseases’: ‘Cataract, AEs regardless of severity’ (MIRASOL study and meta-analysis), ‘dry eye, AE, regardless of severity’ (MIRASOL and FORWARD 1 studies and meta-analysis), ‘eye pain, AE, regardless of severity’ (MIRASOL study and meta-analysis), ‘keratopathy, AE, regardless of severity’ (meta-analysis), ‘photophobia, AE regardless of severity’ (MIRASOL study and meta-analysis), ‘blurred vision, AE regardless of severity’ (MIRASOL and FORWARD 1 studies and meta-analysis) and “reduced visual acuity, regardless of severity” (meta-analysis).
• Overall assessment
  • For the benefit assessment, results on mortality, morbidity, quality of life and side effects from the open-label, randomised, controlled Phase III studies MIRASOL and FORWARD 1, as well as the meta-analysis of these two studies comparing mirvetuximab soravtansin with standard-of-care therapy comprising a choice of paclitaxel, pegylated liposomal doxorubicin and topotecan.
  • For the endpoint of overall survival, the MIRASOL study and the meta-analysis show a statistically significant advantage in favour of mirvetuximab soravtansin. The extent of the prolongation in overall survival achieved is considered a relevant improvement.
  • No evaluable data are available regarding morbidity and health-related quality of life.
  • For the endpoint category of side effects, there are statistically significant advantages in terms of SAEs, severe AEs and therapy discontinuations due to AEs, which are assessed as a clear improvement. In detail, there are both advantages and disadvantages regarding specific AEs.
  • Overall, the G-BA concludes that mirvetuximab soravtansin offers a considerable additional benefit, based on relevant advantages in overall survival and significant advantages regarding side effects.

Courtesy translation only, please refer to the German original.