Nivolumab brings hope to patients with advanced kidney cancer

25 Sep 2015

The targeted drug nivolumab significantly prolongs survival in patients with advanced kidney cancer, whose disease has progressed after their first treatment, according to results of a new phase 3 study.

The CheckMate 025 phase 3 clinical trial, which compared nivolumab with the standard treatment, everolimus, in patients with clear cell renal cell carcinoma (a common type of kidney cancer), is the first to show an improvement in overall survival in these patients for any immune checkpoint inhibitor drug (meaning the therapies that target molecules playing an important role in the immune system’s ability to recognize and attack tumors).

Nivolumab blocks the interaction between the programmed cell death protein 1 (PD-1) and another molecule called programmed cell death protein ligand 1 (PD-L1). However, the survival benefit was seen in patients regardless of the extent of PD-L1 expression in their tumors.

The trial stopped early due to its outstanding results

The international CheckMate 025 phase 3 clinical trial recruited 821 patients with advanced clear cell kidney cancer, who had received prior treatment, between October 2012 and March 2014. They were randomized to receive 3 mg/kg of nivolumab intravenously every two weeks or a 10 mg tablet of everolimus taken orally once a day.

They were followed up for a minimum of 15 months and the data cut-off point for the analysis presented was June 2015, at which point 17% of patients receiving nivolumab and 7% of patients receiving everolimus remained on the treatment. Deaths had occurred among 45% of patients on nivolumab and 54% of patients on everolimus, and the risk of death from any cause was 27% lower among the nivolumab patients.

The trial was stopped early in July 2015 when it became clear that there was superior overall survival among patients being treated with nivolumab. Patients were offered the opportunity to continue with nivolumab treatment or, for those on everolimus, to switch to nivolumab.

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What about the side-effects?

There were fewer serious (grade 3-4) side effects among patients treated with nivolumab: 19% compared to 37% among patients treated with everolimus. The most common side effects were; fatigue (33%), nausea (14%) and severe itching (14%) for nivolumab, and fatigue (34%), inflammation of the mucous membrane of the mouth (30%) and anemia (24%) for everolimus.

There were no treatment-related deaths for nivolumab and two among patients receiving everolimus.

Clinical results

Padmanee Sharma, the Scientific Director of the Immunotherapy Platform and Professor in the Departments of Genitourinary Medical Oncology and Immunology at the MD Anderson Cancer Center, USA reported: “the analysis shows that patients taking nivolumab had a median overall survival of 25 months as compared to 19.6 months for those taking everolimus”.

She commented that the data from this analysis show:

  • a greater proportion of patients had tumors that shrank in response to nivolumab than to everolimus;
  • the objective response rate was 25% for nivolumab versus 5.4% for everolimus,
  • the partial response rate was 24.1% versus 4.9%,
  • the complete response rate was 1% versus 0.5% respectively, and
  • many other patients experienced stable disease when the tumors did not grow – 34.4% for nivolumab-treated patients versus 55.2% for everolimus-treated patients.

“The finding that overall survival was higher among patients treated with nivolumab, irrespective of PD-L1 expression, suggests that PD-L1 expression should not be used to determine which patients might respond to the therapy and whether or not offer it to them,” says Prof Sharma.

Source: eCancer News
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