Durvalumab–savolitinib duo has potential in metastatic papillary renal cell carcinoma
medwireNews: Patients with metastatic papillary renal cell carcinoma (RCC) are likely to benefit from the durvalumab–savolitinib combination, show findings from the 1-year follow-up of the CALYPSO trial.
As reported at the 2020 Genitourinary Cancers Symposium in San Francisco, California, USA, 41 patients with metastatic papillary RCC received the PD-L1 inhibitor durvalumab 1500 mg every 4 weeks and the MET inhibitor savolitinib 600 mg once daily, with a 4-week run-in, over a median follow-up of 14.3 months.
The data, presented by Thomas Powles (Barts Cancer Institute, London, UK) on behalf of Cristina Suárez (Hospital General Universitari Vall d’Hebron, Barcelona, Spain) showed a confirmed objective response rate (ORR) of 27% and a median progression free survival (PFS) of 4.9 months.
This is “[c]omparable to previous drugs that we see and use in this space,” Powles noted. The median overall survival was 12.3 months, which he described as “promising, but not necessarily ground-breaking.”
Powles pointed out that the trial is not “exclusively a frontline trial,” because approximately half of the patients had previously been treated with VEGF inhibitors, but for the 27 patients with no prior VEGF-inhibitor treatment, the confirmed ORR was 33%.
When they looked at MET and PD-L1 biomarkers, the researchers found that the ORR was 40% among MET-positive patients, compared with 25% among PD-L1-positive patients. But Powles warned that the confidence intervals were very wide in those who tested positive for MET and the population size was small, at just 10.
These results, together with the previously reported interim response rate (RR) and progression-free survival (PFS) data, therefore suggest that “[t]he combination of savolitinib and durvalumab has clinical activity in [papillary] RCC,” irrespective of PD-L1 and MET expression, he said.
PD-L1 and MET expression were measured using immunohistochemistry, and while this is the standard for measuring PD-L1, Powles said that DNA alterations need to be looked at in addition to protein expression, which he predicts is “going to turn out to be really important.”
There was an indication of a durable remission in subsets of patients, said Powles, but “it doesn’t look, from a distance, that these two drugs [...] are synergistic with one another.” From the data, he could not currently conclude whether durable remission occurs “because of the PD-L1 therapy, the combination, or MET inhibition.”
He concluded that “the rationale is clearly strong. I think the results are encouraging, but not ground-breaking with [regard to] response, progression-free, and overall survival.”
The investigators plan to extend this study and further explore how the biomarkers are influencing survival among patients receiving durvalumab and savolitinib in combination.
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This independent news story was supported by an educational grant from Pfizer and Merck KGaA