Durvalumab (8) – Imfinzi®

Primarily advanced or recurrent endometrial cancer, combination with carboplatin and paclitaxel; maintenance therapy, combination with olaparib

Characteristics

Start date 01.09.2024 – Marketing authorisation: 26.07.2024
Resolution 20.02.2025
INN Durvalumab
Brand name Imfinzi®
Pharm. company AstraZeneca GmbH
G-BA Procedure ID D-1096
ATC code L01FF03 PD-1/PDL-1 inhibitors (L01FF)
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

Imfinzi in combination with carboplatin and paclitaxel is indicated for the first-line treatment of primary advanced or recurrent endometrial cancer in adults who are eligible for systemic therapy, followed by maintenance treatment with Imfinzi in combination with olaparib in endometrial cancer with mismatch repair failure (pMMR).

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- primary advanced disease,- recurrent disease;- patients 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 to treat- primary advanced disease,- recurrent disease;- patients 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

a) Female patients with newly diagnosed disease

  • The conclusion is that, for the group of patients with a newly diagnosed disease, durvalumab in combination with carboplatin and paclitaxel, followed by durvalumab and olaparib, provides considerable additional benefit.
  • The certainty of the 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 durvalumab in combination with carboplatin and paclitaxel, followed by durvalumab and olaparib.
    • The extent of the prolongation in overall survival achieved is assessed as a marked improvement.
  • Morbidity – Dyspnoea
    • For the endpoint of dyspnoea (assessed using the EORTC QLQ-C30), a statistically significant disadvantage was observed with durvalumab in combination with carboplatin and paclitaxel, followed by durvalumab plus olaparib.
  • Morbidity – loss of appetite
    • For the endpoint of loss of appetite (assessed using the EORTC QLQ-C30), there was a statistically significant disadvantage compared to durvalumab in combination with carboplatin and paclitaxel, followed by durvalumab plus olaparib.
  • Morbidity – constipation
    • For the endpoint of constipation (assessed using the EORTC QLQ-C30), there was a statistically significant difference in favor of durvalumab in combination with carboplatin and paclitaxel, followed by durvalumab plus olaparib.
  • Morbidity – Patient Global Impression of Severity (PGIS)
    • No statistically significant difference was observed between the treatment groups for symptoms assessed using the PGIS.
  • 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.
  • 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 adverse events), there was a statistically significant disadvantage for durvalumab in combination with carboplatin and paclitaxel, followed by durvalumab and olaparib, compared with placebo in combination with carboplatin and paclitaxel, followed by placebo.
  • Overall assessment
    • In the overall analysis, 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, no additional benefit is identified for durvalumab in combination with carboplatin and paclitaxel, followed by durvalumab and olaparib, in patients with recurrent disease.
  • mortality
    • In the patient population with recurrent disease, no statistically significant difference was observed between the treatment arms; consequently, no advantage can be inferred here.
  • Morbidity – Patient Global Impression of Severity (PGIS)
    • No statistically significant difference was observed between the treatment groups in terms of symptoms assessed using the PGIS.
  • 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.
  • 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 adverse events), there was a statistically significant disadvantage for durvalumab in combination with carboplatin and paclitaxel, followed by durvalumab and olaparib, compared with placebo in combination with carboplatin and paclitaxel, followed by placebo.
  • Overall assessment
    • 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, moderate disadvantages are observed.

Courtesy translation only, please refer to the German original.

Associated procedures

Durvalumab (12) Imfinzi® AstraZeneca GmbH Oncological diseases Adenocarcinoma of the stomach or the gastro-oesophageal junction; neoadjuvant and adjuvant combination with FLOT chemotherapy followed by adjuvant monotherapy n.d. active procedure
Durvalumab (11) Imfinzi® AstraZeneca GmbH Oncological diseases Muscle-invasive bladder cancer (MIBC), neoadjuvant/adjuvant therapy following cystectomy, in combination with gemcitabine and cisplatin 4,310–5,730 100% Indication of minor additional benefit
Durvalumab (10) Imfinzi® AstraZeneca GmbH Oncological diseases Non-advanced small cell lung cancer, following platinum-based chemoradiotherapy, monotherapy 670–1,750 100% Indication of considerable additional benefit
Durvalumab (9) Imfinzi® AstraZeneca GmbH Oncological diseases Non-small cell lung cancer, EGFR/ALK-negative, neoadjuvant/adjuvant therapy, in combination with platinum-based chemotherapy 4,540–4,660 100% additional benefit not proven
Durvalumab (7) Imfinzi® AstraZeneca GmbH Oncological diseases Primarily advanced or relapsed endometrial cancer, first-line therapy, combination with carboplatin and paclitaxel; maintenance therapy 380–1,520 100% additional benefit not proven
Durvalumab (8) Imfinzi® AstraZeneca GmbH Oncological diseases Primarily advanced or recurrent endometrial cancer, combination with carboplatin and paclitaxel; maintenance therapy, combination with olaparib 990–1,810 50% Indication of considerable additional benefit
Durvalumab (6) Imfinzi® AstraZeneca GmbH Oncological diseases Hepatocellular carcinoma, first-line, monotherapy 1,900–5,470 100% additional benefit not proven
Durvalumab (3) Imfinzi® AstraZeneca GmbH Oncological diseases Biliary tumors, first-line, combination with gemcitabine and cisplatin 1,800 100% Indication of minor additional benefit
Durvalumab (4) Imfinzi® AstraZeneca GmbH Oncological diseases Non-small cell lung cancer, EGFR/ALK-negative, first-line, combination with tremelimumab and platinum-based chemotherapy 14,470–24,660 100% additional benefit not proven
Durvalumab (5) Imfinzi® AstraZeneca GmbH Oncological diseases Hepatocellular carcinoma, first-line, combination with tremelimumab 1,900–5,470 100% additional benefit not proven
Durvalumab (2) Imfinzi® AstraZeneca GmbH Oncological diseases Small cell lung cancer (SCLC), first-line, combination with etoposide and either carboplatin or cisplatin 3,210–6,130 100% Hint for minor additional benefit
Durvalumab (1) Imfinzi® AstraZeneca GmbH Oncological diseases Non-small cell lung carcinoma (NSCLC), maintenance therapy 1,600–1,800 100% Hint for considerable additional benefit


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