Clinical Trial Review: KEYNOTE-426
Panelists discuss how the KEYNOTE-426 trial established pembrolizumab plus axitinib as an effective and well-tolerated immunotherapy-tyrosine kinase inhibitor (IO-TKI) combination with high response rates and unprecedented tumor control, particularly suitable for frail patients due to axitinib's selective targeting and short half-life.
Video content above is prompted by the following:
Pembrolizumab plus axitinib emerged as the first FDA-approved IO-TKI combination for first-line clear cell renal cell carcinoma, building upon impressive phase 2 data showing 70% response rates. Rini details the phase 3 results demonstrating a 60% objective response rate, nearly 12% complete response rate, and progression-free survival advantage with a HR of approximately 0.6. The initial overall survival HR of 0.53 represented the lowest ever reported, though this advantage diminished over time, characteristic of IO-TKI combinations showing more dramatic early effects.
The regimen's tolerability profile stands out among IO-TKI combinations, attributed to axitinib's selective VEGF receptor inhibition and clean toxicity profile. Common adverse effects include hypertension, hoarseness, fatigue, and diarrhea, but the combination avoids many off-target effects seen with other TKIs. Axitinib's short half-life enables rapid dose adjustments, making it particularly suitable for older patients, those with poor performance status, or patients with cardiovascular comorbidities requiring careful blood pressure management.
Five-year follow-up data, while not as extensive as CheckMate 214's 9-year data, demonstrate sustained benefit with approximately 25% of patients completing the planned 2-year immunotherapy course. The high tumor control rate (90% of patients achieving at least stable disease) makes this regimen attractive for patients requiring reliable disease control. Community oncologists frequently choose this combination due to its familiarity, established safety profile, and predictable management strategies. The regimen particularly appeals to practitioners seeking an effective IO-TKI option with a lower toxicity burden, though head-to-head comparisons with other IO-TKI combinations remain unavailable.
