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Nivolumab active in metastatic non-clear cell renal cell carcinoma

MIAMI — Nivolumab monotherapy demonstrated antitumor activity in a heterogenous population of patients with non-clear cell renal cell carcinoma, according to retrospective study results presented at International Kidney Cancer Symposium.

Nivolumab (Opdivo, Bristol-Myers Squibb), a PD-1 inhibitor, also appeared well tolerated.

“In the absence of available prospective data, this study lends support to the use of nivolumab for patients with metastatic non-clear cell renal cell carcinoma,” Vadim S. Koshkin, MD, of Cleveland Clinic Taussig Cancer Institute, and colleagues wrote.

Non-clear cell renal cell carcinoma accounts for 15% to 20% of kidney malignancies. Treatment strategies often are extrapolated from prospective trials of patients with clear cell renal cell carcinoma, according to study background.

The FDA has approved nivolumab for metastatic renal cell carcinoma; however, the trials that led to regulatory approval only included patients with clear cell histology. Consequently, even though nivolumab is used to treat patients with non-clear cell histology, the agent’s activity in this population has not been well described.

Koshkin and colleagues retrospectively analyzed data from 41 patients (median age, 58 years; range, 33-82; 71% men; 68% white) with histologically confirmed metastatic non-clear cell renal cell carcinoma who received at least one dose of nivolumab monotherapy at one of six U.S. centers between December 2015 and June of this year.

The majority of patients had ECOG performance status of 0 (40%) or 1 (47%). Most were considered either favorable risk or intermediate risk by Memorial Sloan Kettering Cancer Center criteria (85%) and International Metastatic Renal Cell Carcinoma Database Consortium criteria (89%).

Seventy-three patients had undergone prior nephrectomy and 92% had undergone at least one prior systemic therapy. The most common prior therapies were sunitinib (Sutent, Pfizer; 63%), pazopanib (Votrient, Novartis; 27%), axitinib (Inlyta, Pfizer; 10%), everolimus (Afinitor, Novartis; 10%), cabozantinib (Cabometyx, Exelixis; 7%) and gemcitabine/cisplatin (7%). One patient (2%) had received prior immunotherapy with atezolizumab (Tecentriq, Genentech), a PD-L1 inhibitor.

Patients received a median seven (range, 1-28) doses of nivolumab, and median treatment duration was 3 months (range, 0-13.1).

All patients had at least one imaging assessment or clinical progression as assessed by the treating physician after initiation of nivolumab treatment.

After median follow-up of 8.5 months (range, 0.6-18.4), median OS had not been reached and median PFS was 3.5 months (95% CI, 1.9-5).

An analysis of 35 evaluable patients showed seven (20%) achieved objective response; all were partial responses. Ten patients (29%) achieved stable disease.

Researchers evaluated best response based on histology. Among 16 evaluable patients with papillary histology, two (14%) achieved partial response and three (21%) achieved stable disease. Among 14 patients with unclassified histology, four (36%) achieved partial response and three (27%) achieved stable disease. Three of five patients with chromophobe histology achieved stable disease, and one of four patients with collecting duct histology achieved partial response.

Among responders, median time to best response was 5.1 months (range, 1.2-13.3) and median duration of response had not been reached.

Fifteen patients (37%) experienced treatment-related adverse events. Fourteen patients (34%) experienced treatment-related adverse events that required nivolumab treatment to be put on hold or discontinued, and five patients (12%) experienced adverse events that required hospitalization. No treatment-related deaths occurred.

Thirty-one patients discontinued treatment; 25 (81%) did so due to progression, and six (19%) did so due to intolerance.

Eighteen patients (67%) received subsequent treatments after nivolumab therapy. – by Mark Leiser

For more information:

Koshkin VS, et al. Clinical activity of nivolumab in patients with non-clear cell renal cell carcinoma. Presented at: International Kidney Cancer Symposium; Nov. 3-4, 2017; Miami.

Disclosure: The researchers report no relevant financial disclosures.

MIAMI — Nivolumab monotherapy demonstrated antitumor activity in a heterogenous population of patients with non-clear cell renal cell carcinoma, according to retrospective study results presented at International Kidney Cancer Symposium.

Nivolumab (Opdivo, Bristol-Myers Squibb), a PD-1 inhibitor, also appeared well tolerated.

“In the absence of available prospective data, this study lends support to the use of nivolumab for patients with metastatic non-clear cell renal cell carcinoma,” Vadim S. Koshkin, MD, of Cleveland Clinic Taussig Cancer Institute, and colleagues wrote.

Non-clear cell renal cell carcinoma accounts for 15% to 20% of kidney malignancies. Treatment strategies often are extrapolated from prospective trials of patients with clear cell renal cell carcinoma, according to study background.

The FDA has approved nivolumab for metastatic renal cell carcinoma; however, the trials that led to regulatory approval only included patients with clear cell histology. Consequently, even though nivolumab is used to treat patients with non-clear cell histology, the agent’s activity in this population has not been well described.

Koshkin and colleagues retrospectively analyzed data from 41 patients (median age, 58 years; range, 33-82; 71% men; 68% white) with histologically confirmed metastatic non-clear cell renal cell carcinoma who received at least one dose of nivolumab monotherapy at one of six U.S. centers between December 2015 and June of this year.

The majority of patients had ECOG performance status of 0 (40%) or 1 (47%). Most were considered either favorable risk or intermediate risk by Memorial Sloan Kettering Cancer Center criteria (85%) and International Metastatic Renal Cell Carcinoma Database Consortium criteria (89%).

Seventy-three patients had undergone prior nephrectomy and 92% had undergone at least one prior systemic therapy. The most common prior therapies were sunitinib (Sutent, Pfizer; 63%), pazopanib (Votrient, Novartis; 27%), axitinib (Inlyta, Pfizer; 10%), everolimus (Afinitor, Novartis; 10%), cabozantinib (Cabometyx, Exelixis; 7%) and gemcitabine/cisplatin (7%). One patient (2%) had received prior immunotherapy with atezolizumab (Tecentriq, Genentech), a PD-L1 inhibitor.

Patients received a median seven (range, 1-28) doses of nivolumab, and median treatment duration was 3 months (range, 0-13.1).

All patients had at least one imaging assessment or clinical progression as assessed by the treating physician after initiation of nivolumab treatment.

After median follow-up of 8.5 months (range, 0.6-18.4), median OS had not been reached and median PFS was 3.5 months (95% CI, 1.9-5).

An analysis of 35 evaluable patients showed seven (20%) achieved objective response; all were partial responses. Ten patients (29%) achieved stable disease.

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Researchers evaluated best response based on histology. Among 16 evaluable patients with papillary histology, two (14%) achieved partial response and three (21%) achieved stable disease. Among 14 patients with unclassified histology, four (36%) achieved partial response and three (27%) achieved stable disease. Three of five patients with chromophobe histology achieved stable disease, and one of four patients with collecting duct histology achieved partial response.

Among responders, median time to best response was 5.1 months (range, 1.2-13.3) and median duration of response had not been reached.

Fifteen patients (37%) experienced treatment-related adverse events. Fourteen patients (34%) experienced treatment-related adverse events that required nivolumab treatment to be put on hold or discontinued, and five patients (12%) experienced adverse events that required hospitalization. No treatment-related deaths occurred.

Thirty-one patients discontinued treatment; 25 (81%) did so due to progression, and six (19%) did so due to intolerance.

Eighteen patients (67%) received subsequent treatments after nivolumab therapy. – by Mark Leiser

For more information:

Koshkin VS, et al. Clinical activity of nivolumab in patients with non-clear cell renal cell carcinoma. Presented at: International Kidney Cancer Symposium; Nov. 3-4, 2017; Miami.

Disclosure: The researchers report no relevant financial disclosures.

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