Outcomes based on age in patients with metastatic renal cell carcinoma treated with first line targeted therapy or checkpoint immunotherapy: Older patients more prone to toxicity.

OBJECTIVES

Older patients with metastatic renal cell carcinoma (mRCC) were underrepresented in pivotal trials.

MATERIALS AND METHODS

Consecutive patients with mRCC treated at Aarhus University Hospital with first line tyrosine kinase inhibitors (TKI), mTOR inhibitors, or checkpoint immunotherapy (CPI) were retrospectively analyzed in age-subgroups; ≥ 75, 65-74, and < 65 years, with overall survival (OS), time-to-treatment discontinuation (TTD), and progression-free survival (PFS) as endpoints. Hazards ratios were adjusted (aHR) for International Metastatic RCC Database Consortium (IMDC) risk factors, histology, and age.

RESULTS

Of 838 patients, 159 (19%) were ≥ 75 years, 324 (39%) 65-74 years, and 355 (42%) < 65 years. Treatments were TKI in 729 (87%) patients, mTOR in 43 (5%) and CPI in 67 (8%). Older patients ≥ 75 years compared with 65-74 years and < 65 years had lower toxicity-adjusted median doses of pazopanib, 300 mg vs. 400 mg vs. 600 mg, respectively, (p < 0.001), and sunitinib, 25 mg vs. 37.5 mg vs. 50 mg, respectively (p < 0.001); numerically fewer doses of CPI, median 2 vs. 5 vs. 5, respectively, (p = 0.2); a higher proportion had dose reduction/interruption, 76% vs. 55% vs. 41%, respectively, (p < 0.001); and shorter mean time to dose reduction/interruption, 0.5 months vs. 1.9 months vs. 3.4 months, respectively, (p < 0.001). After adjusting IMDC prognostic factors and histology in multivariate analyses, age did not impact OS (aHR 1.0; 95% CI 0.99-1.02, p = 0.2), TTD (aHR 1.0; 95% CI 0.99-1.01, p = 0.4) or PFS (aHR 1.0, 95% CI 0.99-1.01; p = 0.9).

CONCLUSION

Older patients with mRCC were more prone to toxicity; but age did not impact outcomes. Proactive dose modification/interruption and awareness may help to reduce toxicity while maintaining efficacy.