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R. Shah
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-075 - Afatinib Dose Adjustment: Effect on Safety, Efficacy and Patient-Reported Outcomes in the LUX-Lung 3/6 Trials in EGFRm+ NSCLC (ID 9365)
09:30 - 09:30 | Author(s): R. Shah
- Abstract
Background:
Afatinib 40mg/day is approved globally for first-line treatment of EGFR mutation-positive (EGFRm+) NSCLC. Afatinib is available in several tablet strengths (20/30/40/50mg), and tolerability-guided dose adjustment schemes are well established. Here, we evaluate the impact of afatinib dose reduction on safety (AEs), pharmacokinetics, PFS and patient-reported outcomes (PROs) in the Phase III LUX-Lung (LL) 3 and 6 trials.
Method:
Treatment-naïve patients with stage IIIB/IV EGFRm+ NSCLC in LL3/6 received either 40mg/day afatinib or chemotherapy. In case of any treatment-related grade ≥3 AEs or selected prolonged grade 2 AEs, afatinib dose was reduced by 10mg decrements (minimum dose 20mg/day). In this post-hoc analysis of all afatinib-treated patients in LL3/6 (n=229/n=239), we compared incidence and severity of common AEs before and after dose reduction, afatinib plasma concentrations in patients who reduced to 30mg versus those remaining on 40mg, and PFS in patients with/without dose reductions in the first 6 months of treatment. PROs were measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire and the EQ-5D™ health status self-assessment questionnaire, and pooled data from both trials were assessed before/after dose reduction; these included scores on the EORTC Global Health/Quality of Life scale (GH/QoL; 0–100), EORTC Performance Functioning scale (PF; 0–100), EQ Visual Analogue Scale (VAS; 0–100) and EQ-5D UK utility scale (EQ UK utility; 0–1).
Result:
Dose reductions occurred in 122/229 (53.3%) patients in LL3 and 67/239 (28.0%) in LL6; >80% of dose reductions occurred in the first 6 months of treatment. Dose reductions decreased the incidence of treatment-related AEs (grade ≥3 AEs before/after dose reduction: LL3, 73%/20%; LL6, 81%/12%), and were more likely among patients who had higher afatinib plasma concentrations prior to subsequent dose reduction (Day 22). On Day 43, geometric mean afatinib plasma concentrations were comparable between patients who had dose reduced (n=59; 23.3ng/mL) and patients who remained on 40mg (n=284; 22.8ng/mL). Median PFS was comparable between patients with or without dose reductions in the first 6 months (LL3: 11.3 versus 11.0 months; HR [95% CI] 1.25 [0.91–1.72]; p=0.175; LL6: 12.3 versus 11.0 months; 1.00 [0.69–1.46]; p=0.982). There were no clinically meaningful changes in PROs following afatinib dose reduction: GH (40/30mg: 59.1/66.9; n=136); PF (79.4/83.0; n=136); EQ VAS (70.1/75.1; n=135); EQ UK utility (0.70/0.78; n=135).
Conclusion:
Tolerability-guided dose adjustments effectively reduced afatinib-related AEs without negatively affecting therapeutic efficacy and PROs.
