Takeaway
- Protocol-defined dose adjustment of afatinib may allow patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) to remain on treatment longer, maximising clinical benefit, even in the presence of radiological disease progression.
Why this matters
- Dose reduction of afatinib appears to be an effective strategy for the management of treatment-related adverse events (TRAEs), without negatively impacting efficacy.
- It is important to note that there are currently no clinical data to support adaptation of the approved afatinib starting dose based on patient clinical characteristics, and underdosing at initiation of treatment may negatively affect clinical benefit.
- The findings suggest progression in target lesions alone may not be the only factor requiring treatment discontinuation; patients may still derive clinical benefit from continued EGFR TKI treatment.
Key results
- 63 patients had afatinib dose reductions.
- Dose reduction decreased TRAE incidence/severity (before vs after; all grade/grade 3: 100.0%/63.5% vs 90.5%/23.8%).
- No evidence of significant difference in progression-free survival (PFS) with <40 mg/day vs ≥40 mg/day for the first 6 months (hazard ratio [HR] 1.34; 95% CI 0.90-2.00).
- 24 and 26 patients continued afatinib and gefitinib, respectively, beyond progression in target lesions; median time from nadir of target lesion diameters to initial progression was 6.7 months and 5.6 months.
- Of these patients, 79.2% and 76.9%, respectively, had objective response or non-complete response/non-progressive disease in non-target lesions at initial progression.
Study design
- Post-hoc analysis of data from the randomised phase IIb LUX-Lung 7 trial of afatinib 40 mg/day (n=160) or gefitinib 250 mg/day (n=159).
- Afatinib could be reduced by 10 mg decrements to minimum 20 mg.
- As gefitinib is only approved as one dose formulation, only dose interruptions were permitted.
- Funding: Boehringer Ingelheim Pharmaceuticals Inc.
References
References
