Pembrolizumab (32) – Keytruda®
Adenocarcinoma of the stomach or gastroesophageal junction, PD-L1 expression ≥ 1, HER2, first-line, combination with fluoropyrimidine- and platinum-based chemotherapy
Characteristics
| Start date | 01.01.2024 – Marketing authorisation: 24.06.2021 |
|---|---|
| Resolution | 20.06.2024 |
| INN | Pembrolizumab |
| Brand name | Keytruda® |
| Pharm. company | MSD Sharp & Dohme GmbH |
| G-BA Procedure ID | D-1024 |
| ATC code | L01FF02 PD-1/PDL-1 inhibitors (L01FF) |
| ICD-10 codes (AIS) | C16.0Malignant neoplasm of cardiac orifice, C16.1Malignant neoplasm of fundus of stomach, C16.2Malignant neoplasm of body of stomach, C16.3Malignant neoplasm of gastric antrum, C16.4Malignant neoplasm of prepylorus, C16.5Malignant neoplasm of lesser curvature of stomach, not classifiable to C16.1-C16.4, C16.6Malignant neoplasm of greater curvature of stomach, not classifiable to C16.0-C16.4, C16.8Malignant neoplasm of overlapping sites of stomach, C16.9Gastric cancer NOS |
| Alpha-ID codes (AIS) | I103100Malignant neoplasm of the gastroesophageal junction, I107038Malignant neoplasm of the anterior stomach wall n.c, I17994Stomach cancer, I25400Malignant neoplasm of the pylorus, I29937Malignant neoplasm of the ventricular fundus, I29941Malignant neoplasm of the corpus ventriculi, I29944Malignant neoplasm of the antrum pyloricum, I29947Malignant neoplasm of the small curvature of the stomach, I29950Malignant neoplasm of the large gastric curvature |
| Therapeutic area | Oncological diseases Adenocarcinoma (AC) |
| Reason for procedure | New therapeutic indication |
| Specialty | Bundling ACT change |
| Therapeutic indication of the resolution |
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KEYTRUDA is indicated in combination with fluoropyrimidine- and platinum-based chemotherapy for the first-line treatment of locally advanced unresectable or metastatic HER2-negative adenocarcinoma of the stomach or gastroesophageal junction in adults with PD-L1-expressing tumors (CPS ≥ 1) |
| Subpopulation | Indication | Comparator |
|---|---|---|
| Adults with locally advanced, unresectable or metastatic HER2-negative adenocarcinoma of the stomach or gastroesophageal junction (GEJ) with PD-L1-expressing tumors (CPS ≥ 1); first-line therapy | - cisplatin + capecitabine or - oxaliplatin + capecitabine or – cisplatin + S-1 (tegafur/gimeracil/oteracil) or – Cisplatin + 5-fluorouracil (only for patients with adenocarcinoma of the oesophagus) or - Cisplatin + 5-fluorouracil + folinic acid (only for patients with adenocarcinoma of the oesophagus) or – epirubicin + cisplatin + capecitabine or – epirubicin + cisplatin + 5-fluorouracil or – Epirubicin + oxaliplatin + capecitabine or – docetaxel + cisplatin + 5-fluorouracil or – Nivolumab in combination with fluoropyrimidine- and platinum-based combination chemotherapy (only for tumors with PD-L1 expression (Combined Positive Score [CPS] ≥ 5)) or – 5-fluorouracil + oxaliplatin + epirubicin (only for patients with adenocarcinoma of the oesophagus) |
Studies and Results
|
No. of studies
(best subpopulation) |
2 (KEYNOTE-859, KEYNOTE-062) |
|---|---|
|
Study design
(best subpopulation) |
H2H vs. ACT |
|
Meta analysis
(best subpopulation) |
yes |
| ACT change | 09.01.2024 – Änderung der wissenschaftlichen Erkenntnisse |
- Clinical trials
- KEYNOTE 062 is a completed, multicentre, randomised controlled trial (RCT) comparing pembrolizumab as monotherapy with pembrolizumab in combination with chemotherapy, consisting of cisplatin + capecitabine or cisplatin + 5-FU, and against placebo in combination with this chemotherapy.
- KEYNOTE 859 is a double-blind, multicentre RCT comparing pembrolizumab in combination with chemotherapy, consisting of cisplatin + 5-FU or oxaliplatin + capecitabine, with placebo in combination with this chemotherapy.
Adults with locally advanced, unresectable or metastatic HER2-negative adenocarcinoma of the stomach or the gastro-oesophageal junction (GEJ) with PD-L1-expressing tumours (CPS ≥ 1); first-line treatment
- An additional benefit is not proven.
- mortality
- The meta-analytical summary of the Keynote 859 and Keynote 062 studies shows a statistically significant advantage in survival time for the endpoint of overall survival with treatment using pembrolizumab + chemotherapy compared with chemotherapy, consisting of cisplatin + 5-fluorouracil or cisplatin + capecitabine or oxaliplatin + capecitabine.
- The results from the Keynote 859 study show a median difference of 1.6 months, whilst no data on median survival were available for the KEYNOTE 062 study.
- Taking into account the effect estimates from the individual studies and the meta-analytic summary, a relevant improvement can be observed at the endpoint level; however, it is not possible to reliably determine the extent of this advantage, which is minor but nevertheless significant.
- The data presented on morbidity, health-related quality of life and side effects are considered unassessable, as key requirements for evidence of additional benefit are deemed not to have been met and this data set as a whole does not permit a proper assessment.
- Overall assessment
- Consequently, it is not possible, amongst other things, to weigh up the only minor advantage in the overall survival endpoint against the endpoints in the categories of morbidity, health-related quality of life and side effects.
- In the overall assessment, therefore, no additional benefit can be established with the requisite certainty.
Courtesy translation only, please refer to the German original.
Associated procedures
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