Olaparib (12) – Lynparza®

a) Patients with newly diagnosed disease

• The conclusion is that, for the group of patients with a newly diagnosed disease, olaparib in combination with durvalumab as maintenance therapy following first-line treatment with durvalumab in combination with carboplatin and paclitaxel provides considerable additional benefit.
• The certainty of evidence for the identified additional benefit is classified as an indication.
• mortality
  • For the endpoint of overall survival, a statistically significant advantage was observed in the patient population of patients with newly diagnosed disease for olaparib in combination with durvalumab as maintenance therapy following first-line treatment with durvalumab in combination with carboplatin and paclitaxel.
  • The extent of the prolongation in overall survival achieved is assessed as a significant improvement.
• Morbidity – Dyspnoea
  • For the endpoint of dyspnoea (assessed using the EORTC QLQ-C30), there is a statistically significant disadvantage for olaparib in combination with durvalumab in maintenance therapy following first-line treatment with durvalumab in combination with carboplatin and paclitaxel.
• Morbidity – loss of appetite
  • For the endpoint of loss of appetite (assessed using the EORTC QLQ-C30), there was a statistically significant disadvantage for olaparib in combination with durvalumab in maintenance therapy following first-line treatment with durvalumab in combination with carboplatin and paclitaxel.
• Morbidity – constipation
  • For the endpoint of constipation (assessed using the EORTC QLQ-C30), there was a statistically significant disadvantage for olaparib in combination with durvalumab in maintenance therapy following first-line treatment with durvalumab in combination with carboplatin and paclitaxel.
• Morbidity – Patient Global Impression of Severity (PGIS)
  • For the symptoms assessed using the PGIS, there was no statistically significant difference between the treatment groups.
• Health-related quality of life – Cognitive functioning
  • For the endpoint of cognitive functioning (assessed using the EORTC QLQ-C30), there was no statistically significant difference between the treatment groups.
• Health-related quality of life – sexual enjoyment
  • No suitable data are available for the endpoint of sexual enjoyment (assessed using the EORTC QLQ-EN24), as a maximum of 29 versus 25 patients (15% versus 13%) had a baseline value and a further value recorded during the course of the study.
• Side effects – severe adverse events (CTCAE grade ≥ 3)
  • For the endpoint of severe adverse events, there was no statistically significant difference between the treatment groups.
• Side effects – Anaemia (severe adverse events)
  • For the endpoint of anaemia (severe AEs), there was a statistically significant disadvantage for olaparib in combination with durvalumab in maintenance therapy following first-line treatment with durvalumab in combination with carboplatin and paclitaxel, compared with the appropriate comparator therapy.
• Side effects – myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) (serious adverse events)
  • For the MDS/AML endpoint (SUEs), no events occurred in either treatment arm; there was no statistically significant difference between the treatment groups.
• Side effects – pneumonitis (severe adverse events)
  • For the endpoint of pneumonitis (severe adverse events), there was no statistically significant difference between the treatment groups.
• Overall view
  • On balance, the clear advantage in terms of overall survival is offset by moderate disadvantages in endpoints within the morbidity category.
  • These disadvantages do not call into question the extent of the improvement in overall survival.
  • No difference relevant to the benefit assessment was identified for the endpoint categories of health-related quality of life and side effects.

b) Patients with recurrent disease

• Consequently, the G-BA finds no additional benefit for olaparib in combination with durvalumab as maintenance therapy following first-line treatment with durvalumab in combination with carboplatin and paclitaxel, compared with carboplatin in combination with paclitaxel, followed by a watch-and-wait approach for patients with recurrent disease, the G-BA finds no additional benefit in its summary interpretation of the data.
• Morbidity – Dyspnoea
  • For the endpoint of dyspnoea (assessed using the EORTC QLQ-C30), there was a statistically significant disadvantage for olaparib in combination with durvalumab as maintenance therapy following first-line treatment with durvalumab in combination with carboplatin and paclitaxel.
• Morbidity – loss of appetite
  • For the endpoint of loss of appetite (assessed using the EORTC QLQ-C30), there was a statistically significant disadvantage for olaparib in combination with durvalumab in maintenance therapy following first-line treatment with durvalumab in combination with carboplatin and paclitaxel.
• Morbidity – constipation
  • For the endpoint of constipation (assessed using the EORTC QLQ-C30), there was a statistically significant disadvantage for olaparib in combination with durvalumab in maintenance therapy following first-line treatment with durvalumab in combination with carboplatin and paclitaxel.
• Morbidity – Patient Global Impression of Severity (PGIS)
  • For the symptoms assessed using the PGIS, there was no statistically significant difference between the treatment groups.
• Health-related quality of life – Cognitive functioning
  • For the endpoint of cognitive functioning (assessed using the EORTC QLQ-C30), there was no statistically significant difference between the treatment groups.
• Health-related quality of life – sexual enjoyment
  • No suitable data are available for the endpoint of sexual enjoyment (assessed using the EORTC QLQ-EN24), as a maximum of 29 versus 25 patients (15% versus 13%) had a baseline value and a further value recorded during the course of the study.
• Side effects – severe adverse events (CTCAE grade ≥ 3)
  • For the endpoint of severe adverse events, there was no statistically significant difference between the treatment groups.
• Side effects – Anaemia (severe adverse events)
  • For the endpoint of anaemia (severe AEs), there was a statistically significant disadvantage for olaparib in combination with durvalumab in maintenance therapy following first-line treatment with durvalumab in combination with carboplatin and paclitaxel, compared with the appropriate comparator therapy.
• Side effects – myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) (serious adverse events)
  • For the MDS/AML endpoint (SUEs), no events occurred in either treatment arm; there was no statistically significant difference between the treatment groups.
• Side effects – pneumonitis (severe adverse events)
  • For the endpoint of pneumonitis (severe adverse events), there was no statistically significant difference between the treatment groups.
• Overall view
  • Overall, no differences relevant to the benefit assessment were observed in the endpoint categories of overall survival, health-related quality of life and side effects.
  • With regard to morbidity, there are moderate disadvantages.

Courtesy translation only, please refer to the German original.