High BMI Tied to Better Overall Survival in Immune Checkpoint Inhibitor-Treated Metastatic RCC

By Marilynn Larkin

March 15, 2021

NEW YORK (Reuters Health) - In patients with metastatic renal cell carcinoma (mRCC) treated with PD-1/PD-L1-based immune checkpoint inhibitors (ICIs), higher body mass index was associated with improved overall survival in a database study.

"These findings shine light on the 'obesity paradox' in advanced RCC," Dr. Aly-Khan Lalani of the Juravinski Cancer Centre in Hamilton, Ontario, and Dr. Toni Choueiri of Dana-Farber Cancer Institute in Boston told Reuters Health by email.

"Our results, taken in context of the contemporary era of immune checkpoint blockade, are consistent with and build upon analyses previously performed in the era of single-agent targeted therapies," they said. "This paradox appears persistent in RCC throughout the evolving systemic therapy landscape."

"Broadly, these data highlight the importance of optimizing both how we assess, and address, patient factors that influence cancer care outcomes," they said. "BMI is feasibly captured in clinics but may not completely reflect the underlying health status of our patients. Further, cancer cachexia is tied to poor outcomes across solid tumors."

As reported in JAMA Oncology, 735 patients with mRCC and a recorded BMI were treated with PD-1/PD-L1-based ICI (median age at therapy initiation, 63; about 75% men; 61%, White; 20%, Asian; 2%, Hispanic; 2%, Black).

Overall, 31% received first-line ICI, and 31% received combination ICI (19% with VEGF; 12% with cytotoxic T-lymphocyte-associated protein 4 or other therapies).

At ICI initiation, 37% of patients had low BMI (<25) and 63%, high BMI (25 or higher). The median follow-up was 13.5 months.

Those with a high BMI had significantly improved overall survival (1-year OS: 79% vs. 66%; adjusted hazard ratio, 0.753). The association was consistent in subgroup analyses by sex, IMDC (International Metastatic RCC Database Consortium) group, histology, and type/line of therapy.

Patients with higher BMI also had a numerically higher overall response rate (30% vs. 21%) and longer time to treatment failure (median 7.4 vs. 4.9 months); however, these were not statistically significant in multivariable models (ORR, adjusted odds ratio, 1.51; TTF, aHR, 0.98).

In 319 patients with available next-generation sequencing data, genomic alteration frequencies and tumor mutational burden were similar between BMI groups (6.8 vs. 6.8 mutations per megabase).

Drs. Lalani and Choueiri noted, "In reflecting on our data, we maintain that robust RCC care should be inclusive of multidisciplinary inputs, such as nutritional and exercise care plans, to offer our patients the best chance at long-term survival."

From a research perspective, they added, "With the recent results from pivotal phase III clinical trials - such as CHECKMATE-9ER (https://bit.ly/3qHupn2) and CLEAR (https://bit.ly/3qJ5ZJO)- there are rich correlative analyses that may help uncover the biology of our findings, which have been noted across other solid tumors."

Dr. Matthew Zibelman, Assistant Professor, Department of Hematology/Oncology, Fox Chase Cancer Center in Philadelphia told Reuters Health by email that the findings "support prior findings in patients with mRCC treated with TKIs; however, it is impossible to know if this association is truly causal or biologic, or merely a surrogate association based on unmeasured or other factors."

"For example, the low BMI group had a higher percent of patients with poor performance status, non-clear cell histology, and IMDC poor risk group, all of which associate with worse survival," he said. "It would be interesting to see if this finding would hold up in a retrospective analysis of a large randomized trial where the patients would be evenly distributed."

SOURCE: https://bit.ly/3qHp67k JAMA Oncology, online March4, 2021.

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