MSI-H = microsatellite instability-high; dMMR = mismatch repair deficient; PD-1 = programmed death receptor-1; CI = confidence interval.
- Biliary
- Bladder
- Breast
- Colorectal
- Endometrial
- Esophageal
- Gastric or GE junction
- Pancreatic
- Prostate
- Renal cell
- Retroperitoneal
adenocarcinoma
- Sarcoma
- Small cell lung
- Small intestinal
- Thyroid
- Biliary
- Bladder
- Breast
- Colorectal
- Endometrial
- Esophageal
- Gastric or
GE junction
- Pancreatic
- Prostate
- Renal cell
- Retroperitoneal
adenocarcinoma
- Sarcoma
- Small cell lung
- Small intestinal
- Thyroid
CRC = colorectal cancer; GE = gastroesophageal.
- The efficacy of KEYTRUDA was evaluated in patients with MSI‑H or dMMR solid tumors enrolled in 1 of 5 uncontrolled, open-label,
multicohort, multicenter, single-arm trials. Patients with active autoimmune disease or a medical condition that required
immunosuppression were ineligible across the 5 trials. Patients received either KEYTRUDA 200 mg every 3 weeks (Q3W)
or KEYTRUDA 10 mg/kg every 2 weeks (Q2W) until unacceptable toxicity; disease progression that was symptomatic, was
rapidly progressive, required urgent intervention, or occurred with a decline in performance status; or a maximum of 24 months.
For the purpose of assessment of anti-tumor activity across these 5 trials, the major efficacy outcome measures were objective
response rate (ORR) as assessed by blinded independent central radiologists’ review according to Response Evaluation Criteria In
Solid Tumors (RECIST) v1.1, modified to follow a maximum of 10 target lesions and a maximum of target lesions per organ, and duration of response (DOR).
Six-site prospective, investigator-initiated trial included patients with CRC (n=28) and non-CRC (n=30) who received KEYTRUDA 10 mg/kg Q2W following ≥2 prior regimens for CRC or ≥1 for non-CRC; tested with local PCR or IHC.
Prospective, international, multicenter trial of patients with CRC (n=61) who received KEYTRUDA 200 mg Q3W following fluoropyrimidine, oxaliplatin, and irinotecan +/- anti-VEGF/EGFR monoclonal antibody; tested with local PCR or IHC.
Retrospectively identified patients (n=6) with PD-L1–positive gastric, bladder, or triple-negative breast cancer who received KEYTRUDA 10 mg/kg Q2W following ≥1 prior regimen; tested with central PCR.
Retrospectively identified patients (n=5) with PD-L1–positive esophageal, biliary, breast, endometrial, or CRC who received KEYTRUDA 10 mg/kg Q2W following ≥1 prior regimen; tested with central PCR.
Prospective, international, multicenter enrollment of patients with MSI-H/dMMR non-CRC and retrospectively identified patients who were enrolled in specific rare-tumor non-CRC cohorts (n=19) who received KEYTRUDA 200 mg Q3W following ≥1 prior regimen; tested with local PCR or IHC (central PCR for patients in rare-tumor non-CRC cohorts).
- A total of 149 patients with MSI‑H or dMMR cancers were identified across the 5 clinical trials. Among these 149 patients, the baseline characteristics were: median age 55 years (36% aged 65 years or older); 56% male; 77% White, 19% Asian, 2% Black; and ECOG PS 0 (36%) or 1 (64%). Ninety-eight percent of patients had metastatic disease and 2% had locally advanced, unresectable disease. The median number of prior therapies for metastatic or unresectable disease was 2. Eighty-four percent of patients with metastatic CRC and 53% of patients with other solid tumors received 2 or more prior lines of therapy.
- The identification of MSI‑H or dMMR tumor status for the majority of patients (135/149) was prospectively determined using local laboratory—developed PCR tests for MSI‑H status or IHC tests for dMMR. Fourteen of the 149 patients were retrospectively identified as MSI‑H by testing tumor samples from a total of 415 patients using a central laboratory—developed PCR test. Forty-seven patients had dMMR cancer identified by IHC, 60 had MSI‑H identified by PCR, and 42 were identified using both tests.
ECOG PS = Eastern Cooperative Oncology Group performance status; EGFR = epidermal growth factor receptor; IHC = immunohistochemistry; PCR = polymerase chain reaction; PD‑L1 = programmed death ligand 1; VEGF = vascular endothelial growth factor.
aAll recommendations are category 2A unless otherwise indicated.2‑11,13‑16
bCategory 2B recommendation.12
cPembrolizumab should be considered for certain patients with dMMR or MSI-H adrenocortical tumors.16
Category 2A = Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.2‑11,13‑16
Category 2B = Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.12
NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.