Axitinib dose titration

Background

Phase II RCT of 213 patients with treatment-naïve metastatic RCC who received axitinib 5mg BID during a 4-week lead-in. Patients with no BP issues (BP <150/90 mm Hg, ≤2 antihypertensives) and no grade 3-4 treatment-related AE were randomized to dose titration versus placebo titration.

Interventions and follow up

Arm A: Axitinib titrated to 7mg BID, then to 10mg BID if tolerated
Arm B: Placebo dose titration (axitinib 5mg BID)
Primary endpoint: ORR in randomized patients

Results

ORR (A vs B): 54% vs 34%, one-sided P=.019
Lead-in/non-randomized cohort ORR: 59%

Adverse events

Grade 3+ in titration arm (A vs B): hypertension 18% vs 9%, diarrhea 13% vs 4%
Tolerability: dose titration was feasible and allowed individualized dosing in selected patients

Conclusions

Axitinib dose titration in selected patients tolerating the starting dose improved ORR, supporting individualized dosing.

Key Limitations

Phase II, ORR endpoint without PFS/OS benefit demonstrated; only patients tolerating lead-in were randomized, limiting generalizability; predates IO-based first-line therapy.

Clinical Context

Provided rationale for the axitinib dose-titration strategy reflected in product labeling. ESMO guidance on VEGFR-TKI dosing supports individual titration based on tolerability; clinical relevance is now mainly in TKI-based regimens after IO therapy.

References