PD-L1 inhibition well-tolerated, active in metastatic RCC

Jan 19 2016

By Shreeya Nanda, Senior medwireNews Reporter

The programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has a favourable toxicity profile and shows anti-tumour activity in previously treated patients with metastatic renal cell carcinoma (RCC), according to phase Ia trial findings.

David McDermott (Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA) and co-researchers say that atezolizumab is now being evaluated in combination with other therapies, such as bevacizumab, for first-line treatment in this patient population.

They add: “These trials will clarify the role for atezolizumab…in RCC and will explore the interplay between antiangiogenesis-targeted therapy and cancer immunotherapy.”

Of the 70 patients in the RCC cohort of an ongoing phase Ia dose-escalation and dose-expansion trial of atezolizumab, 90% had clear cell histology and 10% had non-clear cell disease. Initially patients were recruited irrespective of PD-L1 status, but subsequently only those harbouring tumours with at least 5% PD-L1–positive tumour infiltrating immune cells were enrolled.

Atezolizumab was administered intravenously every 3 weeks at doses ranging from 3–20 mg/kg, although one patient was given a flat 1200 mg dose. The median number of doses was 12, corresponding to a median treatment duration of 8 months.

Seventeen percent of study participants experienced a grade 3 treatment-related adverse event, with fatigue (4%) and anaemia (4%) being the most common, and 4% experienced a grade 3 immune-mediated adverse event. No side effects of grade 4 or 5 were observed in the study, but 4% of patients discontinued treatment as a result of a related toxic effect.

After a median follow-up of 23.9 months, progression-free survival and overall survival were a median of 5.6 and 28.9 months, respectively, for the 63 clear cell RCC patients assessed for survival outcomes. And an objective response per RECIST criteria was achieved by 15% of the 62 evaluable patients.

Interestingly, the objective response rate was an “impressive” 22% for the 18 patients with high Fuhrman grade and/or sarcomatoid features, both of which are generally associated with poor prognosis, reports the team.

Outcomes varied by PD-L1 expression, such that patients with less than 1% of PD-L1–positive tumour infiltrating immune cells had a shorter median overall survival and lower objective response rate than those with at least 1% of PD-L1–positive cells, at 28.8 months versus not reached and 9% versus 18%, respectively.

The researchers conclude in the Journal of Clinical Oncology: “Atezolizumab demonstrated a manageable safety profile and promising antitumor activity in patients with metastatic RCC.”

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