renal cell carcinoma

Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients with Advanced Non–Clear Cell Renal Cell Carcinoma

Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients with Advanced Non–Clear Cell Renal Cell Carcinoma

In the March 20, 2021 edition of Journal of Clinical Oncology, David F. McDermott and colleagues report on the results of pembrolizumab monotherapy as first line treatment in advanced non-clear cell renal cell carcinoma.

PURPOSE

Investigators report on the nonclear cell renal cell carcinoma components of the phase II KEYNOTE-427 study (cohort B), with pembrolizumab monotherapy in patients with untreated advanced RCC

METHODS

To qualify for the study, patients needed to have histologically confirmed nonclear cell RCC, and were than randomized to monotherapy with pembrolizumab 200 mg intravenously once every 3 weeks for up to 2 years with a primary endpoint of overall response rate.

RESULTS

165 patients were unrolled, 71.5% with confirmed papillary, 12.7% with chromophobe, and 15.8% with unclassifiable RCC histology.  The majority of patients (67.9%) had either intermediate or poor risk per IMRCCDC stratification and tumors with PD-L1 combined positive score (CPS) ≥ 1 (61.8%). The median time from enrollment to database cutoff was 31.5 months (range, 22.7-38.8).  Across all patients, the overall response rate was 26.7%. The median DOR was 29.0 months; 59.7% of responses lasted for more than 1 year. The ORR by CPS 1 or higher and CPS less than 1 status were reported as 35.3% and 12.1%, respectively. The overall response rate by histology was 28.8% for papillary, 9.5% for chromophobe, and 30.8% for unclassifiable. The median PFS was 4.2 months (95% CI, 2.9 to 5.6); the 2-year rate was 18.6%. The median OS was 28.9 months (95% CI, 24.3 months to not reached); the 2-year rate was 58.4%.  The authors reported that overall, 69.7% of patients had reported treatment-related adverse events, most commonly pruritus (20.0%) and hypothyroidism (14.5%).  2 of the reported deaths were unfortunately treatment related (cardiac arrest and pneumonitis).

The authors concluded “First-line pembrolizumab monotherapy showed promising antitumor activity in nccRCC. The safety profile was similar to that observed in other tumor types.”

https://ascopubs.org/doi/full/10.1200/JCO.20.02365

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