Olaparib (12) – Lynparza®
Primarily advanced or recurrent endometrial cancer with pMMR, combination with durvalumab, maintenance therapy
Characteristics
| Start date | 01.09.2024 – Marketing authorisation: 12.08.2024 |
|---|---|
| Resolution | 20.02.2025 |
| INN | Olaparib |
| Brand name | Lynparza® |
| Pharm. company | AstraZeneca GmbH |
| G-BA Procedure ID | D-1095 |
| ATC code | L01XK01 PARP inhibitors (L01XK) |
| ICD-10 codes (AIS) | C54.1Malignant neoplasm of endometrium |
| Alpha-ID codes (AIS) | I27788Endometrial carcinoma |
| Therapeutic area | Oncological diseases Endometrial cancer (EC) |
| Reason for procedure | New therapeutic indication |
| Specialty | Bundling Combination therapy |
| Therapeutic indication of the resolution |
|---|
|
Adult patients with primary advanced endometrial carcinoma (stage III or IV) or recurrent endometrial carcinoma with mismatch repair deficiency (pMMR) who have not yet received any systemic therapy for the treatment of primary advanced – have not yet received systemic therapy as postoperative or adjuvant therapy for the treatment of primary advanced disease, – have not yet received chemotherapy for the recurrence; maintenance therapy |
| Subpopulation | Indication | Comparator |
|---|---|---|
| a) | Adult patients with primary advanced endometrial carcinoma (stage III or IV) or recurrent endometrial carcinoma with mismatch repair failure (pMMR) who have not yet received systemic therapy as postoperative or adjuvant therapy to treat- the primary advanced disease,- the recurrence; maintenance therapyPatients with newly diagnosed disease | Carboplatin + paclitaxel followed by watchful waiting |
| b) | Adult patients with primary advanced endometrial carcinoma (stage III or IV) or recurrent endometrial carcinoma with mismatch repair failure (pMMR) who have not yet received systemic therapy as postoperative or adjuvant therapy for the treatment of- primary advanced disease- recurrence; maintenance therapyPatients with recurrent disease | Carboplatin + paclitaxel followed by watchful waiting |
Studies and Results
|
No. of studies
(best subpopulation) |
1 (DUO-E) |
|---|---|
|
Study design
(best subpopulation) |
H2H vs. ACT |
|
Meta analysis
(best subpopulation) |
no |
| Reason for dividing into subpopulations (G-BA) | Previous treatment |
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.
Associated procedures
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