Argilés, Guillem

3637 Background: In the CORRECT phase III trial, the multikinase inhibitor REG demonstrated significant improvement in overall survival and progression-free survival vs placebo (P) in patients with mCRC whose disease had progressed on other standard therapies. The most frequent grade 3 AEs were hand–foot skin reaction (HFSR), fatigue, diarrhea, hypertension, and rash. We examined when these AEs first occurred and what impact they had on REG dosing. Methods: Adults with mCRC progressing after all standard therapies were randomized to receive REG 160 mg (n=505) or P (n=255) orally once daily for the first 3 weeks of each 4-week cycle. AEs were managed with dose modifications (reduction and interruption) according to the protocol. Results: The safety population comprised 753 pts (REG n=500, P n=253). The mean ± SD treatment duration was 12.1 ± 9.7 weeks for REG and 7.8 ± 5.2 weeks for P. Treatment-emergent AEs occurred in 99.6% of REG pts and 96.8% of P pts. AEs occurring in ≥10% more REG than P pts were fatigue, HFSR, anorexia, diarrhea, weight loss, voice changes, hypertension, rash/desquamation, oral mucositis, fever, hyperbilirubinemia, and low platelet count. The incidence of grade ≥3 HFSR, fatigue, hypertension, and rash/desquamation typically peaked in cycle 1 and tapered to a relatively stable lower incidence over later cycles, while the incidence of diarrhea remained relatively constant throughout the study; median time to first occurrence and worst grade of these AEs is shown in the table. AEs led to dose modifications in 66.6% of REG pts and 22.5% of P pts. Conclusions: The most common AEs in the REG group typically occurred early during treatment. Close early monitoring of AEs and proper management by dose modification is recommended. Clinical trial information: NCT01103323. [Table: see text]

3636 Background: In the CORRECT phase III trial, the multikinase inhibitor REG demonstrated significant improvement in overall survival (OS) and progression-free survival vs placebo (Pla) in patients (pts) with mCRC whose disease progressed on other standard therapies. The most frequent REG-related grade ≥3 adverse events (AEs) of interest were hand–foot skin reaction (HFSR), fatigue, diarrhea, hypertension, and rash/desquamation. We explored whether the impact of REG in pts aged ≥65 years differed from that in younger patients. Methods: Pts with mCRC progressing following all other available therapies were randomized 2:1 to receive REG 160 mg once daily (n=505) or Pla (n=255) for the first 3 weeks of each 4-week cycle. The dose could be modified to manage AEs. The primary endpoint was OS. We report efficacy, safety, and dosing data from REG recipients by age. Results: The REG treatment group included 309 pts <65 years (307 evaluable for safety) and 196 pts ≥65 years (193 evaluable for safety). The OS hazard ratio (REG/Pla) was 0.72 (95% confidence interval [CI] 0.56–0.91) in pts <65 years and 0.86 (95% CI 0.61–1.19) in pts ≥65 years (interaction p-value = 0.405). Median OS was 6.7 vs 5 months for REG vs Pla in pts <65 years, and 6.0 vs 5.6 months, respectively, in pts ≥65 years. Most pts experienced drug-related AEs (<65 years: 93.8%; ≥65 years: 91.7%). The rates of grade ≥3 REG-related AEs of interest and dose modifications are shown in the Table. In pts <65 years vs ≥65 years, median (interquartile range [IQR]) duration of REG was 7.6 weeks (6.6–15.4) vs 7.1 weeks (5.1–17.2), median (IQR) daily REG dose was 160.0 mg (134.6–160.0) vs 160.0 mg (137.5–160.0), and median (IQR) proportion of planned REG dose was 83.3% (65.7–100.0) vs 78.6% (66.7–100.0), respectively. Conclusions: In the CORRECT trial, REG demonstrated an OS benefit in pts <65 years and ≥65 years. Safety and tolerability of REG appeared to be similar in both age subgroups. Clinical trial information: NCT01103323. [Table: see text]