“I don’t think we knew what to expect here, because immunotherapy has struggled both in chemotherapy pretreated and in chemotherapy-naive patients,” said Tanya Dorff, MD, head of the genitourinary cancers program at City of Hope Cancer Center in Duarte, California. “Ipilimumab as monotherapy didn’t fare well in the pre-chemo cohort any more than in the post-chemo cohort. It is too small of a study to draw many conclusions about which cohorts might be better targeted, but there is a trend towards more response in [the] chemo-naive cohort,” noted Dr Dorff.

“In general — not just for immunotherapies — patients who receive fewer pretreatments do better,” said Xiao Wei, MD, medical oncologist specializing in genitourinary cancers at the Dana-Farber Cancer Institute in Boston, Massachusetts. “They typically have better biology, lower tumor burden, and [fewer] resistance mechanisms,” added Dr Wei.

The median PFS was 5.5 months in the chemotherapy-naive cohort and 3.8 months in the chemotherapy pretreated cohort. The median OS was 19 months and 15.2 months, respectively.


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“PFS and OS cannot be compared to other treatments, as this is not a randomized trial. The PFS is relatively short, which is disappointing, but it might just be an early report of the data, since the authors do indicate responders were ongoing at the time of data cut-off,” said Dr Dorff.

Despite modest numbers for PFS and OS, 2 patients in each cohort experienced complete responses (CR) to the combination treatment. And more clues may lie in a patient’s tumor mutational burden (TMB) count.

“The authors don’t present a full analysis of these patients, but if you look at the complete responders, 3 have high TMB. TMB appears to be one good selector about which patients at least to exclude from these treatments, as TMB-low status seems to predict which patients will not respond and shouldn’t be exposed to this treatment regimen with significant toxicity,” said Dr Dorff.

Two of the patients with a CR also had a mutation in their homologous recombination repair pathways; 1 patient did not, and for another patient, these data were unavailable.

“What could have been interesting to see: patient level information about the burden of disease, as well as the size of disease,” said Dr Wei. “In my opinion, a patient with a large burden of disease — for example, involving the liver who had a CR — is very different from a patient with borderline large lymph nodes with a CR.”