A RANDOMIZED PHASE II STUDY OF AXITINIB PLUS PEMETREXED/CISPLATIN (PEM/CIS) FOR NON-SMALL-CELL LUNG CANCER (NSCLC)

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Abstract

Background

Axitinib is a potent and selective second-generation inhibitor of VEGF receptors 1-3. We evaluated efficacy and safety of axitinib plus pem/cis in patients, including Japanese, with NSCLC.

Methods

Patients with confirmed stage IIIB, IV, or recurrent non-squamous NSCLC, and ECOG PS 0 or 1 were randomized 1:1:1 (stratified by gender and PS) to receive up to six 21-day cycles of axitinib continuously + pem/cis (arm I); axitinib on days 2–19 followed by a 3-day interruption + pem/cis (arm II); or pem/cis alone (arm III). Axitinib starting dose was 5 mg BID. Pem/cis (500/75 mg/m2) was infused on day 1 of each cycle. Primary end point was progression-free survival (PFS).

Results

Baseline patient characteristics in arms I (n = 55), II (n = 58), and III (n = 57) included 59–62 year median age; 62–65% male; 5–20% Japanese; and 43–47% PS 0. Median PFS in arms I, II, and III was 8.0, 7.9, and 7.1 months, respectively; hazard ratios (arm I versus III and II versus III) were 0.892 (95% CI 0.560–1.423; P = 0.355) and 1.019 (0.640–1.623; P = 0.545), respectively. Median overall survival was 16.6, 14.7, and 15.9 months for arms I, II, and III, respectively; hazard ratios (arm I versus III and II versus III) were 1.079 (0.663–1.756; P = 0.632) and 1.391 (0.871–2.222; P = 0.891). The objective response rate for arm I (45.5%) was significantly (P = 0.013) higher than in arm III (26.3%), but the difference between arms II (39.7%) and III did not reach statistical difference (P = 0.069). Common grade 3 or 4 adverse events in arms I, II, and III, respectively, were (%) hypertension (20, 17, 0), neutropenia (18, 12, 9), nausea (18, 5, 7), vomiting (15, 5, 4), fatigue (11, 16, 16), and anemia (9, 14, 11). In 17 Japanese patients, grade 3 or 4 hypertension (%) was higher in axitinib-containing arms (64, 67, 0), but was manageable with medications.

Conclusions

No significant differences in PFS or OS were seen between axitinib-containing arms compared with pem/cis alone. Combination therapy was generally tolerated in overall and Japanese patients.

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