KEYNOTE-427 updates confirm pembrolizumab benefit for advanced RCC
medwireNews: The latest findings from the KEYNOTE-427 trial add to the efficacy evidence for first-line pembrolizumab against advanced or metastatic renal cell carcinoma (RCC) regardless of histology.
The results for the clear cell (cc) and non-cc histology patient cohorts were reported in two posters presented at the ESMO Congress 2019 in Barcelona, Spain, by James Larkin (Royal Marsden Hospital NHS Foundation Trust, London, UK) and Cristina Suárez (Vall d’Hebron University Hospital, Barcelona, Spain), respectively.
All patients in the study were assigned to receive pembrolizumab 200 mg every 3 weeks and assessed for response at week 12 and again at 6-week intervals until week 54, and at 12-week intervals thereafter.
The objective response rate (ORR) for the 110 patients with ccRCC was 36.4%, with a “meaningful” response achieved for patients regardless of whether they had favorable- or intermediate/poor-risk IMDC prognostic score (31.0 vs 39.7%), a PD-L1 combined positive score (CPS) of less than or at least 1 (29.3 vs 44.2%), or sarcomatoid features (63.6%).
The median time to response in the full cohort was 2.8 months, and the median duration of response (DOR) was unreached, with responses lasting at least 1 year in over 60% of responding patients. Median progression-free survival (PFS) was 7.1 months and median overall survival (OS) was unreached, Larkin et al said.
“These results provide support for the exploration of pembrolizumab in the adjuvant setting (KEYNOTE-564) and inform outcomes with pembrolizumab combinations for patients with advanced RCC,” the team concluded.
Findings for the non-ccRCC patient cohort, updated from an earlier report at ASCO GU 2019, continue to show “promising antitumor activity” after a median 15.0 months of follow-up, Suárez and team said.
The ORR was 26.1% for the 165 patients, with 43 patients continuing treatment at time of data cutoff. Responses were achieved across all subgroups, including patients with papillary (28.0%), chromophobe (9.5%) and unclassified (30.8%) histologies, or sarcomatoid features (42.1%), as well as for those with an IMDC risk category of favorable (32.1%) or intermediate/poor (23.2%). The ORR was 10.3% for patients with a CPS of less than 1 versus 35.3% for those with a CPS of 1 or more.
For the whole cohort, responses occurred after a median of 2.8 months and DOR was a median 15.3 months with 57% of responding patients continuing to do so after 12 months, ranging from 40–73% of the subgroups.
“Although the ORR seemed greater and more [complete responses] occurred in patients with favorable IMDC risk, the DOR seemed higher in patients with intermediate or poor IMDC risk,” the investigators observed.
They also found that patients who experienced an 80% or greater reduction in target lesions tended to experience a “durable OS benefit.” Median PFS for the non-ccRCC cohort was 4.1 months and median OS was unreached.
The team added that “[t]he safety profile was as expected based on the previously described safety profile of pembrolizumab in other tumor types,” in line with that reported for the ccRCC cohort.
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This independent news article was supported by an educational grant from Pfizer and Merck KGaA