Metastatic Chromophobe RCC Outcomes Similar to Clear Cell in Targeted Therapy

metastatic chromophobe renal cell carcinoma: metastatic chromophobe renal cell carcinomaCHICAGO—In a poster session at ASCO 2016, Steven Yip, MD, MSc, FRCPC, presented what he called the first-ever study on outcomes in the metastatic chromophobe renal cell carcinoma (RCC) patient population. “There really is not much data available on rare subtypes,” he acknowledged. “My mentor worked with the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), so we wanted to look into how it responded in the targeted therapy area. Most of the existing data was in the pre-targeted therapy area. Because this disease is so rare, the data is limited. We had the largest amount of patient information and studied it internationally.” Defining Metastatic Chromophobe RCC RCC subtypes are typically classified according to the cancer cells' appearance under a microscope. Patients with chromphobe RCC have pale cells similar to those with clear cell RCC, the most common form of the disease. However, chromophobe RCC cells are usually much larger and have enough molecular differences from clear cell RCC that researchers from the Cancer Genome Atlas insist the two subtypes be regarded as clinically distinct diseases. Chromophobe RCC is a genetic condition and runs in families in conjunction with Birt-Hogg-Dubé syndrome. RCCs tend to metastasize in seemingly random patterns. Once this occurs, the disease is considered incurable. Chromophobe RCC is associated with stronger survival odds than clear cell carcinomas, with a 5-year survival rate between 92-94 percent. “Incidences of metastatic chromophobe RCC are extremely rare, with only 6-7 percent of all metastatic RCCs (mRCC) considered chromophobe,” explained Yip. “Based upon the fact that this type of cancer is so uncommon, none of the data addresses the sunitinib and sorafenib era.” Study Methodology To clarify outcomes in the current immunotherapy era, Yip and his team performed a retrospective analysis of 4,970 patients in the IMDC. Patients were stratified into low-, medium-, and high-risk groups. All the patients received one or more lines of targeted therapy for the metastatic RCC. A small minority—56 percent of patients were male. Out of 105 patients studied, 51 were classified as anemic. A much smaller representation of patients, 15 and 14 respectively, had thrombocytosis and neutrophilia. Yip and the team relied on the Karnofsky Performance Status measures, which gauge patients' ability to complete everyday tasks in a scale of one to 100. The closer the score to 100, the greater the patients' skill at performing tasks. In this study, 19 out of 105 patients had Karnofsky Performance Status ≤ 80. Nearly half the patients, 48 out of 114 were diagnosed less than 1 year before beginning first-line therapy. Sunitinib was the most popular first-line therapy, with 68 out of 113 patients on the prescription regimen. Other therapeutic agents included sorafenib (16/113 patients), pazopanib (12/113 patients), temsirolimus (11/113 patients), everolimus (5/113 patients), and bevacizumab (1/113 patients). A total of 49 people received second-line therapies. Of the mRCC patients treated with the targeted therapies in Yip's study, 109 out of the 4,970, or 2 percent, had metastatic chromophobe RCC. The rest had clear cell mRCC. Overall and progression-free survival rates; time to treatment failure; overall, partial, and complete response rates; and stable and progressive disease were calculated. Evaluating Outcomes Likely the most important factor, survival data was relatively similar in both subgroups. Here, the risk stratification made a significant difference, as researchers expected. “Earlier research in IMDC risk stratification criteria found that these factors had big impact on outcomes, especially those stratified in low, intermediate, and high risk,” remarked Yip. “When combined, all these factors we uncovered had an appropriate reflection in stratifying just like we'd see in clear cell RCCs.” In this study, patients with IMDC favorable criteria (18%) had median overall survival of 31.4 months. Those with intermediate risk (59%) achieved an overall survival of 27.3 months, and poor risk patients (23%) had overall survival of 4.8 months. Overall survival ran parallel for patients with metastatic chrRCC to those with in the clear cell sub-group of RCC. Metastatic chrRCC patients overall survival was calculated at 23.8 months, while those with clear cell RCC had an overall survival rate of 22.4 months. “Overall survival was quite similar,” confirmed Yip. “It's possible that earlier data prior to the targeted therapy era found similar metastatic outcomes. The fact that they're still similar in the age of sunitinib is very encouraging.” Time to treatment failure in both mRCC subgroups was comparable as well. Patients in the chrRCC group showed time to treatment failure of 6.9 months versus 7.6 months for those diagnosed with clear cell RCC. By and large, sunitinib emerged as the strongest treatment regimen. When utilized as a first-line therapy in the metastatic chrRCC group, survival rates stood at 60 percent. The next highest producer of survival rates was sorafenib at 15 percent. “Future research needs to focus on larger groupings,” remarked Yip. “We'll also need to assess this rare type with novel therapies such as nivolumab and immunotherapies.” Still, this early research study will have an immediate effect on patient care. When prescribed first-line treatment, patients with chrRCC will experience similar outcomes as those with the most common form of clear cell RCC. “In the past, we didn't have a clear understanding of whether this treatment was applicable to such a rare subtype,” concluded Yip. “Now that we've presented at ASCO and disseminated data, we can tell our patients in clinic that there's good grounded evidence for why we can treat them similarly to how we would patients with clear cell RCC.” Robin Hocevar is a contributing writer.