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Use of the PD-L1 inhibitor atezolizumab (Tecentriq) with or without radiotherapy (RT) demonstrated some antitumor activity in patients with advanced penile cancer in the phase II trial, but the study ultimately failed to meet its primary endpoint.

Among 30 evaluable patients, the 1-year progression-free survival (PFS) rate was 12.5%, well short of the study's goal of 35% or greater, reported Hielke-Martijn de Vries, MD, of the Netherlands Cancer Institute in Amsterdam, during his presentation at the Genitourinary Cancers Symposium.

As for secondary outcomes, the 1-year overall survival (OS) rate was 43.4%, with a median OS of 11.5 months, although these data were immature. The overall response rate was 33%, with three complete responses and seven partial responses. Eight of the responses were in the atezolizumab plus RT arm (two complete and six partial).

While this prospective trial did not meet its primary endpoint, it "demonstrated some durable and complete responses in this advanced disease where there is a high risk of mortality," noted discussant Hao G. Nguyen, MD, PhD, of the University of California San Francisco.

The evaluation of the tumor microenvironment in previous studies in this setting showed that high-risk human papillomavirus (HPV) was present in 25% to 50% of patients and PD-L1 expression was positive in 40% to 60% of patients, de Vries said. These patients had a high number of intratumoral CD8 T cells, "creating for us a rationale for immunotherapy," he added.

PERICLES included 32 patients (median age 67) with stage IV squamous cell carcinoma of the penis and a WHO performance status of 0 or 1. Previous treatment with anti-PD-1/L1 inhibitors was not allowed. A quarter of the patients had received no prior treatment, and 59% had distant metastases.

All patients received atezolizumab 1,200 mg every 3 weeks for a maximum of 1 year. Cohort A consisted of 20 patients who also received 33 fractions of 1.5 to 1.8 Gy of locoregional RT. Cohort B consisted of 12 patients who received atezolizumab only.

Twenty patients (63%) experienced an immunotherapy-related adverse event, and three had grade 3 or 4 adverse events. Of the patients who received RT, 90% experienced an adverse event of any kind and 65% had a grade 3 or 4 adverse event, but de Vries noted that most of these were caused by a lymphocyte count decrease that was clinically insignificant in 50% of patients.

PFS and OS rates were slightly better in PD-L1-positive and high-risk HPV-positive patients. "It is interesting here to notice that the two patients in arm B who responded well to treatment were both PD-L1-positive and high-risk HPV-positive," de Vries said.

"This could be an important finding in terms of selecting patients who may benefit from immunotherapy," Nguyen added, suggesting that more research is needed to assess PD-L1 positivity and high-risk HPV as biomarkers.

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