KEYTRUDA is indicated for the first-line treatment of patients with advanced MSI-H or dMMR colorectal cancer (CRC).
- 40% REDUCTION IN THE RISK OF DISEASE PROGRESSION OR DEATH with KEYTRUDA vs chemotherapy (HRb=0.60; 95% CI, 0.45–0.80; Pc=0.0004).
- Double the median PFS with KEYTRUDA: 16.5 months (95% CI, 5.4–32.4) vs 8.2 months (95% CI, 6.1–10.2) with chemotherapy.
- Events observed: 54% (n=82/153) with KEYTRUDA vs 73% (n=113/154) with chemotherapy.
- OS data were not mature (66% of the required number of events for the OS final analysis) at time of analysis.
Median follow-up time was 27.6 months (range 0.2 to 48.3 months).
aAs assessed by BICR according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
bBased on Cox regression model.
cTwo-sided P value based on log-rank test (compared to a significance level of 0.0234).
BICR = blinded independent central review; CI = confidence interval; dMMR = mismatch repair deficient; HR = hazard ratio; MSI-H = microsatellite instability-high; PD-1 = programmed death receptor-1; OS = overall survival; PFS = progression-free survival; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors v1.1.
dBased on confirmed response by BICR.
eBased on observed DOR.
+ Denotes ongoing response.
ORR = objective response rate; CR = complete response; PR = partial response; DOR = duration of response.
fPatients randomized to chemotherapy were offered KEYTRUDA at the time of disease progression.
The efficacy of KEYTRUDA was investigated in KEYNOTE-177, a multicenter, randomized, open-label, active-controlled trial that enrolled 307 patients with previously untreated unresectable or metastatic MSI-H or dMMR CRC. MSI or MMR tumor status was determined locally using polymerase chain reaction (PCR) or immunohistochemistry (IHC), respectively. Patients with autoimmune disease or a medical condition that required immunosuppression were ineligible. Patients were randomized (1:1) to receive KEYTRUDA 200 mg intravenously every 3 weeks or investigator’s choice of the following chemotherapy regimens given intravenously every 2 weeks: mFOLFOX6 (oxaliplatin, leucovorin, and FU) or mFOLFOX6 in combination with either bevacizumab or cetuximab: Oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2), and FU 400 mg/m2 bolus on Day 1, then FU 2400 mg/m2 over 46–48 hours. Bevacizumab 5 mg/kg on Day 1 or cetuximab 400 mg/m2 on first infusion, then 250 mg/m2 weekly; FOLFIRI (irinotecan, leucovorin, and FU) or FOLFIRI in combination with either bevacizumab or cetuximab: Irinotecan 180 mg/m2, leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2), and FU 400 mg/m2 bolus on Day 1, then FU 2400 mg/m2 over 46–48 hours. Bevacizumab 5 mg/kg on Day 1 or cetuximab 400 mg/m2 on first infusion, then 250 mg/m2 weekly. Treatment with KEYTRUDA or chemotherapy continued until RECIST v1.1-defined progression of disease as determined by the investigator or unacceptable toxicity. Patients treated with KEYTRUDA without disease progression could be treated for up to 24 months. Assessment of tumor status was performed every 9 weeks. Patients randomized to chemotherapy were offered KEYTRUDA at the time of disease progression. The main efficacy outcome measures were PFS as assessed by BICR according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and OS. Additional efficacy outcome measures were ORR and DOR.
1L = first line; FU = fluorouracil; IV = intravenously; MMR = mismatch repair; MSI = microsatellite instability; Q2W = every 2 weeks; Q3W = every 3 weeks.
ECOG PS = Eastern Cooperative Oncology Group performance status.
Determine MSI/MMR status at diagnosis. Order testing today.
Start with KEYTRUDA for all appropriate patients with advanced MSI-H/dMMR CRC.