Immunotherapy-based regimens show promise in non-clear-cell RCC
medwireNews: Three trials point to the potential of regimens incorporating agents targeting the programmed cell death protein 1 (PD-1) or its ligand (PD-L1) in patients with non-clear-cell renal cell carcinoma (RCC).
The studies were reported at the 2019 ASCO Genitourinary Cancers Symposium in San Francisco, California, USA.
In the first trial, the phase II KEYNOTE-427 trial, which comprised 165 patients who had not received prior treatment for recurrent or metastatic non-clear-cell RCC, treatment with the PD-1 inhibitor pembrolizumab at a dose of 200 mg every 3 weeks led to an objective response rate (ORR) of 24.8% during a median follow-up of 11.1 months.
A third of participants were receiving treatment at data cutoff and the median duration of response was unreached, reported David McDermott (Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA) on behalf of the investigators.
Responses were observed across all histologic subtypes, with ORRs of 25.4%, 9.5%, and 34.6% for the papillary, chromophobe, and unclassified subgroups, respectively.
And the adverse event (AE) profile was “generally as expected,” said McDermott, with 11% of participants experiencing AEs of grade 3–5, most commonly colitis and hepatitis.
He therefore concluded that the findings “support further evaluation of pembrolizumab” in this patient population.
The second study – the phase I/II CALYPSO trial – investigated the combination of the anti-PD-L1 agent durvalumab and the c-MET kinase inhibitor savolitinib in 41 patients with metastatic papillary RCC. Durvalumab was administered at a monthly dose of 1500 mg, while savolitinib was given at a once-daily dose of 600 mg, with a 4-week run-in for savolitinib.
As reported by Cristina Suárez (Hospital General Universitari Vall d’Hebron, Barcelona, Spain), over a median follow-up of 6.9 months, 27% of the participants achieved a response, with a slightly higher rate of 32% for the 28 previously untreated patients.
She noted that the majority of patients derived some clinical benefit from the regimen, with 54% experiencing a decrease in tumor burden. And all but one of the 11 responders remained on treatment at the time of analysis and again the median duration of response had not been reached.
The durvalumab–savolitinib combination was well tolerated; the majority of AEs were of grade 1 or 2, and there was only one incidence of grade 4 toxicity, a case of transaminitis.
Rana McKay, from the University of California San Diego, presented the findings of a phase II trial of the PD-L1 inhibitor atezolizumab plus bevacizumab in patients with non-clear-cell RCC (n=39) or clear-cell RCC with sarcomatoid differentiation (n=17).
A regimen of atezolizumab 1200 mg and bevacizumab 15 mg/kg, both given every 3 weeks, resulted in an ORR of 34%, with responses lasting for a median of 24 weeks.
Of note, the ORRs differed by International Metastatic RCC Database Consortium risk status, histologic subtype, and presence of sarcomatoid differentiation. For instance, the ORR was 44% for individuals with sarcomatoid differentiation and 26% for those without.
The regimen was “very well tolerated,” said McKay, with AEs of grade 3 occurring in 37% of patients and no grade 4 or 5 AEs.
And she concluded: “Future studies are warranted to explore immunotherapy and novel combinations in this patient population.”
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