KEYNOTE-177 is a phase 3, randomized open-label study evaluating the efficacy and safety of Pembrolizumab ( Keytruda ) versus standard of care chemotherapy ± Bevacizumab ( Avastin ) or Cetuximab ( Erbitux ) as first-line therapy for patients with microsatellite-instability high / mismatch repair deficient ( MSI-H/dMMR ) metastatic colorectal cancer ( mCRC ).
Results of the final progression-free survival ( PFS ) analysis were presented.
A total of 307 pts with MSI-H/dMMR metastatic colorectal cancer as determined locally and ECOG PS 0 or 1 were randomly assigned 1:1 to first-line Pembrolizumab 200 mg Q3W ( every 3 weeks ) for up to 2 years or investigator’s choice of mFOLFOX6 or FOLFIRI Q2W ( every 2 weeks ) ± Bevacizumab or Cetuximab ( chemotherapy chosen prior to randomization ).
Treatment continued until progression disease, unacceptable toxicity, patient / investigator decision to withdraw, or completion of 35 cycles ( Pembrolizumab only ).
Patients receiving chemotherapy could crossover to Pembrolizumab for up to 35 cycles after confirmed progression disease.
Primary end points were progression-free survival ( RECIST v1.1, central review ) and overall survival ( OS ).
Key secondary end points included objective response rate ( ORR ) ( RECIST v1.1, central review ), and safety.
The data cutoff date for this interim analysis was February 19, 2020. The study will continue without changes to evaluate overall surival.
At data cutoff, 153 patients were randomized to Pembrolizumab and 154 to chemotherapy. Median ( range ) study follow-up was 28.4 months ( 0.2-48.3 ) with Pembrolizumab versus 27.2 months ( 0.8-46.6 ) with chemotherapy.
Pembrolizumab was superior to chemotherapy for progression-free survival ( median 16.5 months vs 8.2 months; hazard ratio, HR=0.60; 95% CI, 0.45-0.80; P=0.0002 ).
The 12- and 24-months PFS rates were 55.3% and 48.3% with Pembrolizumab vs 37.3% and 18.6% with chemotherapy.
Confirmed objective response rate was 43.8% vs 33.1%; median ( range ) duration of response was not reached ( 2.3+ to 41.4+ ) with Pembrolizumab versus 10.6 months ( 2.8 to 37.5+ ) with chemotherapy.
Grade 3-5 treatment related adverse event rates were 22% versus 66% for Pembrolizumab vs chemotherapy. One patient in the chemotherapy arm died due to a treatment-related adverse effects.
In conclusion, Pembrolizumab provided a clinically meaningful and statistically significant improvement in progression-free survival versus chemotherapy as first-line therapy for patients with MSI-H/dMMR metastatic colorectal cancer, with fewer treatment-related adverse effects observed and should be the new standard of care for these patients. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020