Pembrolizumab (23) – Keytruda®

Colorectal cancer (CRC)) with MSI-H or with dMMR, after fluoropyrimidine-based combination therapy.

Characteristics

Start date 01.08.2022 – Marketing authorisation: 25.04.2022
Resolution 19.01.2023
INN Pembrolizumab
Brand name Keytruda®
Pharm. company MSD Sharp & Dohme GmbH
G-BA Procedure ID D-838
ATC code L01FF02 PD-1/PDL-1 inhibitors (L01FF)
ICD-10 codes (AIS) C18.0Malignant neoplasm of ileocecal valve, C18.1Malignant neoplasm of appendix, C18.2Malignant neoplasm of ascending colon, C18.3Malignant neoplasm of hepatic flexure, C18.4Malignant neoplasm of transverse colon, C18.5Malignant neoplasm of splenic flexure, C18.6Malignant neoplasm of descending colon, C18.7Malignant neoplasm of sigmoid colon, C18.8Malignant neoplasm of overlapping sites of colon, C18.9Malignant neoplasm of large intestine NOS, C19Malignant neoplasm of rectosigmoid junction, C20Malignant neoplasm of rectum
Alpha-ID codes (AIS) I104488Malignant neoplasm of the rectosigmoid junction, I115345Carcinoma of the colon and sigmoid colon, I18119Malignant neoplasm of the rectum, I25671Malignant neoplasm of the flexura coli sinistra, I29955Malignant neoplasm of the colon, I29956Malignant neoplasm of the caecum, I29957Malignant neoplasm of the vermiform appendix, I29959Malignant neoplasm of the ascending colon, I29964Malignant neoplasm of the flexura coli dextra, I29966Malignant neoplasm of the transverse colon, I29971Malignant neoplasm of the descending colon, I29972Malignant neoplasm of the sigmoid colon
DDD 9.5 mg P
Therapeutic area Oncological diseases Colorectal cancer (CRC) / Small intestine cancer
Reason for procedure New therapeutic indication
Specialty Bundling

Therapeutic indication of the resolution

Keytruda is indicated as monotherapy of colorectal cancer with MSI-H or with a dMMR as follows in adults:

- For the treatment of unresectable or metastatic colorectal cancer (CRC) after prior fluoropyrimidine-based combination therapy.

Subpopulation Indication Comparator
Adults with non-resectable or metastatic colorectal cancer (CRC) with high-frequency microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR); after prior fluoropyrimidine-based combination therapy. A patient-specific therapy depending on the type and number of previous therapies, the RAS and BRAF mutation status, the location of the primary tumor, the general condition and the risk of toxicity induced by anti-VEGF and anti-VEGFR substances with a choice of: - 5-fluorouracil in combination with folinic acid and irinotecan (FOLFIRI) with or without bevacizumab or aflibercept or ramucirumab - 5-fluorouracil in combination with folinic acid and irinotecan (FOLFIRI) with or without cetuximab or panitumumab (only for patients with RAS wild type) - 5-fluorouracil in combination with folinic acid and oxaliplatin (FOLFOX) with or without bevacizumab - Capecitabine in combination with oxaliplatin (CAPOX) with or without bevacizumab - 5-Fluorouracil in combination with folinic acid with or without bevacizumab - Capecitabine with or without bevacizumab - Irinotecan as monotherapy - Panitumumab as monotherapy (only for patients with RAS wild type) - Cetuximab as monotherapy (only for patients with wild-type RAS) - Trifluridine/tipiracil - Irinotecan in combination with cetuximab (only for patients with wild-type RAS) - Encorafenib in combination with cetuximab (only for patients with BRAF V600E mutation)

Studies and Results

No. of studies
(best subpopulation)
1 (KEYNOTE-164)
Study design
(best subpopulation)
Single-arm + ITC (MAIC)
Meta analysis
(best subpopulation)
no

  • Clinical trials
    • The KEYNOTE-164 trial is a single-arm Phase II trial conducted between August 2015 and February 2021 at 34 trial centres in North America, Europe, Asia and Australia, involving a total of 124 patients.

Adults with metastatic colorectal cancer with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H); following prior fluoropyrimidine-based combination therapy

  • An additional benefit is not proven
  • Overall, the data presented are not sufficient to demonstrate additional benefit compared with the appropriate comparator therapy, and therefore the additional benefit of pembrolizumab as monotherapy is not proven in adult patients with locally advanced, unresectable or metastatic colorectal cancer with MSI-H or dMMR following prior fluoropyrimidine-based combination therapy.
  • Data basis
    • In the dossier for the benefit assessment, the pharmaceutical manufacturer presents the results of the registration trial for pembrolizumab. This is the KEYNOTE-164 trial, which enrolled patients with locally advanced, unresectable or metastatic colorectal cancer with MSI-H or dMMR.
    • In addition, the pharmaceutical manufacturer has submitted indirect comparisons with individual treatment options.
    • Overall, the adjusted and non-adjusted indirect comparisons presented are not suitable for demonstrating additional benefit compared with the appropriate comparator therapy.
  • Conclusion
    • Overall, the data presented are not sufficient to demonstrate additional benefit compared with the appropriate comparator therapy, and therefore the additional benefit of pembrolizumab as monotherapy in adult patients with locally advanced, unresectable or metastatic colorectal cancer with MSI-H or dMMR following prior fluoropyrimidine-based combination therapy is not proven.

Courtesy translation only, please refer to the German original.

Associated procedures

Pembrolizumab (41) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Resectable locally advanced squamous cell carcinoma of the head and neck, PD-L1 expression ≥ 1 per cent, neoadjuvant and adjuvant therapy, in combination with radiotherapy with or without concomitant cisplatin therapy 2,550–4,240 86% Hint for minor additional benefit
Pembrolizumab (40) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Malignant pleural mesothelioma, non-epithelioid, first-line treatment, in combination with pemetrexed and platinum-based chemotherapy 55–105 100% additional benefit not proven
Pembrolizumab (38) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Cervical carcinoma (stage III to IVA), first-line, combination with radiochemotherapy 750 100% Indication of non-quantifiable additional benefit
Pembrolizumab (39) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Endometrial carcinoma, first-line, combination with carboplatin and paclitaxel 1,370–3,330 100% additional benefit not proven
Pembrolizumab (36) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Urothelial carcinoma, non-resectable or metastatic, first-line, combination with enfortumab vedotin 1,050–2,601 39% Indication of considerable additional benefit
Pembrolizumab (37) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Breast cancer, triple-negative, high risk of recurrence, neoadjuvant and adjuvant therapy, monotherapy or combination with chemotherapy 2,440–2,610 50% Indication of minor additional benefit
Pembrolizumab (35) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Non-small cell lung cancer, high risk of recurrence, neoadjuvant and adjuvant therapy, monotherapy or combination with platinum-based chemotherapy 5,090–6,780 100% additional benefit not proven
Pembrolizumab (34) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Non-small cell lung cancer, adjuvant therapy with high risk of recurrence after resection, after prior chemotherapy 2,690–3,200 100% additional benefit not proven
Pembrolizumab (32) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Adenocarcinoma of the stomach or gastroesophageal junction, PD-L1 expression ≥ 1, HER2, first-line, combination with fluoropyrimidine- and platinum-based chemotherapy 285–2,613 100% additional benefit not proven
Pembrolizumab (33) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Biliary tumours, first-line, combination with gemcitabine and cisplatin 1,480–2,180 100% Indication of minor additional benefit
Pembrolizumab (31) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Adenocarcinoma of the stomach or gastroesophageal junction, PD-L1 expression ≥ 1, HER2+, first-line, combination with trastuzumab, fluoropyrimidine- and platinum-based chemotherapy 70–710 100% additional benefit not proven
Pembrolizumab (28) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Cervical carcinoma, PD-L1 expression ≥ 1 (CPS), combination with or without bevacizumab 1,315–1,525 40% Indication of considerable additional benefit
Pembrolizumab (30) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Melanoma, ≥ 12 to < 18 years 1–4 100% additional benefit not proven
Pembrolizumab (22) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Renal cell carcinoma (RCC), adjuvant, monotherapy, pre-treated patients 1,518–1,973 100% Hint for minor additional benefit
Pembrolizumab (23) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Colorectal cancer (CRC)) with MSI-H or with dMMR, after fluoropyrimidine-based combination therapy. 350–1,470 100% additional benefit not proven
Pembrolizumab (24) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Endometrial carcinoma with MSI-H or with dMMR, pre-treated 230–3,360 100% additional benefit not proven
Pembrolizumab (25) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Gastric carcinoma with MSI-H or dMMR, pre-treated 80–110 74% Hint for non-quantifiable additional benefit
Pembrolizumab (26) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Small bowel carcinoma with MSI-H or dMMR, pre-treated 40–380 100% additional benefit not proven
Pembrolizumab (27) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Biliary carcinoma with MSI-H or dMMR, pre-treated 20–150 100% additional benefit not proven
Pembrolizumab (29) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Melanoma, adjuvant therapy, ≥ 12 years, monotherapy 1,621–2,314 100% Indication of non-quantifiable additional benefit
Pembrolizumab (21) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Breast carcinoma (BC), triple-negative (TNBC), high risk of recurrence, neoadjuvant and adjuvant therapy, monotherapy or combination with chemotherapy 0
2,440–2,520
50% Hint for minor additional benefit repealed
Pembrolizumab (19) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Endometrial carcinoma (EC) , after platinum-based therapy, combination with lenvatinib 1,130–5,070 100% Indication of considerable additional benefit
Pembrolizumab (20) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Advanced renal cell carcinoma (RCC), first-line, combination with lenvatinib 2,790–4,189 100% additional benefit not proven
Pembrolizumab (17) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Carcinoma of the esophagus or gastroesophageal junction, PD-L1 expression ≥ 10 (CPS), first-line, combination with platinum- and fluoropyrimidine-based chemotherapy. 535–805 34% Indication of considerable additional benefit
Pembrolizumab (18) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Breast cancer (BC), triple-negative, PD-L1 expression ≥ 10 (CPS), combination with chemotherapy 260–270 50% Hint for considerable additional benefit
Pembrolizumab (14) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Hodgkin lymphoma (HL), pre-treated patients, ≥ 3 years 120–240 46% Hint for considerable additional benefit
Pembrolizumab (16) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Urothelial carcinoma (UC), CPS ≥ 10, first-line 225–380 100% additional benefit not proven
Pembrolizumab (15) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Colorectal carcinoma (CRC) with MSI-H or dMMR, first-line 370–955 87% Hint for minor additional benefit
Pembrolizumab (12) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Renal cell carcinoma (RCC), first-line, combination with axitinib 3,500 23% Indication of considerable additional benefit
Pembrolizumab (13) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Squamous cell carcinoma head and neck, PD-L1 expression ≥ 1%, first-line, combination with platinum and 5-fluorouracil (5-FU) chemotherapy 4,950–5,370 100% Indication of minor additional benefit
Pembrolizumab (11) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Squamous cell carcinoma head and neck, PD-L1 expression ≥ 1%, first-line, monotherapy 4,955–5,370 100% Hint for considerable additional benefit
Pembrolizumab (10) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Non-small cell lung carcinoma (NSCLC), squamous cell histology, first-line, combination with carboplatin and (nab-) paclitaxel 5,340–5,570 71% Hint for considerable additional benefit
Pembrolizumab (9) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Non-small cell lung carcinoma (NSCLC), non-squamous cell histology, first-line, combination with pemetrexed and platinum chemotherapy 8,020–9,120 100% Hint for non-quantifiable additional benefit
Pembrolizumab (8) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Melanoma, adjuvant therapy 2,670–3,400 100% Indication of non-quantifiable additional benefit
Pembrolizumab (7) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Urothelial carcinoma (UC), CPS ≥ 10, first-line 0
240–420
100% additional benefit not proven repealed
Pembrolizumab (6) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Squamous cell carcinoma head and neck 470–3,290 100% additional benefit not proven
Pembrolizumab (5) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Urothelial carcinoma (UC) 0
2,300–3,300
61% Indication of considerable additional benefit repealed
Pembrolizumab (4) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Hodgkin lymphoma (HL) 60–180 100% additional benefit not proven
Pembrolizumab (3) Keytruda® MSD SHARP & DOHME GMBH Oncological diseases Non-small cell lung carcinoma (NSCLC), first-line 4,000 100% Indication of considerable additional benefit
Pembrolizumab (2) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Non-small cell lung carcinoma (NSCLC), after prior chemotherapy 12,500–24,300 40% Indication of considerable additional benefit
Pembrolizumab (1) Keytruda® MSD Sharp & Dohme GmbH Oncological diseases Melanoma 2,500–4,500 71% Indication of considerable additional benefit


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