KEYNOTE-427, a single-arm, open-label, phase 2 study, has shown antitumor activity with first-line Pembrolizumab ( Keytruda ) monotherapy in non-clear cell renal cell carcinoma ( nccRCC ) ( cohort B ).
Studies of renal cell cancer ( RCC ) and immune-oncology have shown that depth of tumor response may correlate with long-term benefit.
Researchers have presented the association between depth of response and overall survival ( OS ) plus updated efficacy and safety data in KEYNOTE-427 cohort B.
Patients with histologically confirmed nccRCC, who did not receive prior systemic therapy, and who have measurable disease ( RECIST v1.1 ) received Pembrolizumab 200 mg IV Q3W for 2 years or until progressive disease, unacceptable toxicity, or withdrawal.
Endpoints were overall response rate [ ORR ] ( primary ), duration of response [ DOR ], and progression-free survival [ PFS ] ( RECIST v1.1 ); overall survival; and safety.
Association between depth of response, defined as maximum reduction from baseline in sum of target lesions, and overall survival was evaluated using a Cox proportional hazards model with target lesion reduction group as time-varying covariate.
Of 165 patients, 72% had papillary histology, 13% had chromophobe histology, and 16% were unclassified.
Median time from enrollment to data cutoff was 18.7 months ( range, 9.9-26.0 ).
ORR was 26.1% ( 95% CI, 19.5-33.5; 10 [ complete response ] CRs, 33 [ partial responses ] PRs ).
Median ( range ) DOR was 15.3 months ( 2.8-21.0+ ); 57.3% had DOR 12 months or more.
At 18-month, PFS rate was 18.9% and OS rate was 67.0%.
Most patients ( 58.8% ) had some reduction in target lesions. Patients with a more than 30% reduction in target lesions had an increased probability of survival.
ORR ( 95% CI ) was similar for papillary ( 28.0% [ 20.1-37.0 ] ) and unclassified ( 30.8% [ 14.3-51.8 ] ) histology but lower for chromophobe ( 9.5% [ 1.2-30.4 ] ).
OS rates at 18 month were 70.8%, 66.7%, and 50.0 in the papillary, chromophobe, and unclassified groups, respectively.
Treatment-related adverse effects ( TRAEs ) occurred in 67.9% of all patients, primarily pruritus ( 19% ), hypothyroidism ( 14% ), and fatigue ( 14% ).
Grade 3-5 TRAEs occurred in 14% of patients; 2 patients died of TRAEs ( pneumonia and cardiac arrest ).
In conclusion, first-line Pembrolizumab monotherapy continued to show antitumor activity in non-clear cell renal cell carcinoma with no new safety concerns.
In general, for patients who had greater reductions in target lesions, the trend was toward improved overall survival; patients with reduction of tumor burden greater than or equal to 80% had comparable long term outcomes to those who achieved a RECIST 1.1 defined complete response. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020