PD-1 blockade via Pembrolizumab ( Keytruda ) monotherapy has shown antitumor activity in relapsed or refractory classic Hodgkin lymphoma ( R/R cHL ).
KEYNOTE-204 was a randomized, international, open-label, phase III study of Pembrolizumab versus Brentuximab vedotin ( Adcetris; BV ) in R/R cHL.
Patients were aged 18 years or more, were post-autologous stem cell transplant ( auto-SCT ) or ineligible for auto-SCT, and had measurable disease and ECOG Performance Status 0 or 1.
BV-naive and BV-exposed patients were eligible.
Patients were randomized 1:1 to Pembrolizumab 200 mg IV Q3W ( once every 3 weeks ) or Brentuximab vedotin 1.8 mg/kg IV Q3W and stratified by prior auto-SCT ( yes versus no ) and status after first-line ( 1L ) therapy ( primary refractory vs relapsed less than 12 months vs relapsed 12 months or more after end of 1L therapy ).
Primary end points were: progression-free survival ( PFS ) by blinded independent central review ( BICR ) per International Working Group ( IWG ) criteria including clinical and imaging data after auto-SCT or allogeneic SCT ( allo-SCT ) and overall survival ( OS ).
Key secondary end points were: PFS excluding clinical and imaging data after auto-SCT or allo-SCT ( PFS-secondary ), and objective response rate ( ORR ) by BICR per IWG, PFS by investigator review per IWG, and safety.
Exploratory end point was: duration of response ( DOR ) by BICR per IWG.
304 patients were randomized and 300 were treated ( 148, Pembrolizumab; 152, Brentuximab vedotin ); 256 discontinued.
Median ( range ) follow-up was 24.7 ( 0.6-42.3 ) months.
15 patients were Brentuximab vedotin exposed.
Median ( range ) time on treatment was 305.0 ( 1-814 ) and 146.5 ( 1-794 ) days with Pembrolizumab and Brentuximab vedotin, respectively.
Statistically significant improvement was observed with Pembrolizumab versus Brentuximab vedotin for primary PFS analysis ( hazard ratio, HR=0.65 [ 95% CI 0.48-0.88; P =0.00271 ]; median 13.2 vs 8.3 months ); 12-months PFS rates were 53.9% vs 35.6%, respectively.
Benefit was observed in all subgroups tested, including patients with no auto-SCT ( HR=0.61 ), primary refractory disease ( HR=0.52 ), prior Brentuximab vedotin ( HR=0.34 ) and Brentuximab vedotin naive ( HR=0.67 ).
Significant improvement in PFS-secondary was observed with Pembrolizumab versus Brentuximab vedotin ( HR=0.62 [ 95% CI 0.46-0.85 ]; median 12.6 vs 8.2 months ).
Per investigator assessment, PFS was longer with Pembrolizumab versus Brentuximab vedotin ( HR=0.49 [ 95% CI 0.36-0.67 ]; median 19.2 vs 8.2 months ).
ORR was 65.6% for Pembrolizumab and 54.2% for Brentuximab vedotin; complete response ( CR ) rates were 24.5% and 24.2%, respectively.
Median ( range ) DOR was 20.7 months ( 0.0+ to 33.2+ ) for Pembrolizumab and 13.8 months ( 0.0+ to 33.9+ ) for Brentuximab vedotin.
Grade 3-5 treatment-related adverse events ( TRAEs ) were observed in 19.6% of patients with Pembrolizumab and 25.0% with Brentuximab vedotin.
One death due to TRAE occurred with Pembrolizumab ( pneumonia ).
In conclusion, in patients with R/R cHL, Pembrolizumab was superior to Brentuximab vedotin and demonstrated statistically significant and clinically meaningful improvement in progression-free survival across all subgroups, with safety consistent with previous reports.
Pembrolizumab monotherapy should be standard of care for this patient population with relapsed or refractory classic Hodgkin lymphoma. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020