Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 27, No 15S (May 20 Supplement), 2009: 5520
© 2009 American Society of Clinical Oncology

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Abstract

A randomized phase II study: Pazopanib (P) versus lapatinib (L) versus combination of pazopanib/lapatinib (L+P) in advanced and recurrent cervical cancer (CC)

UCI Medical Center, Orange, CA; INEN - Medicina, Lima, Peru; Centro Medico San Roque, Tucuman, Argentina; Institut Català d`Oncologia, Hospital Duran I Reyn, Barcelona, Spain; Centre Regional de Lutte contrele Cancer, Marseille, France; Chulalongkorn University, Bangkok, Thailand; GlaxoSmithKline, Collegeville, PA

5520

Background: P and L are oral tyrosine kinase inhibitors. P targets VEGFR, PDGFR, and c-Kit. L targets EGFR and HER2 in CC, EGFR overexpression and markers of angiogenesis correlate with poor outcome; the prognostic value of HER2 overexpression remains unclear. Methods: Patients (pts) with measurable stage IVB, persistent or recurrent squamous or adenocarcinoma of the cervix not amenable to curative therapy; 0–1 prior regimens in the metastatic setting; ECOG PS 0–1; were randomized 1:1:1 to each of 3 treatment groups; not prescreened for EGFR or HER2 status. Treatment consisted of P 800mg QD; L 1,500 mg QD; L+P: P 400 mg + L 1,000 mg QD; the doses were escalated to P 800 mg + L 1,500 mg after 20 pts treated at 400 mg + 1,000 mg. Therapy continued until progression (PD), withdrawal due to adverse events (AEs), or withdrawal of consent. Primary endpoint was progression free survival (PFS); secondary overall survival (OS), tumor response (RR), safety. The study had 85% power to detect 80% improvement in PFS. A hierarchical testing procedure was applied comparing L+P vs L followed by L+P vs P and P vs L. The futility boundary was crossed for L + P vs L at the planned interim analysis and this arm was discontinued. Only the comparison of P vs L at the final analysis is reported. Results: Total N = 235 pts: 152 in the monotherapy arms: P (78); L (74). Baseline characteristics were balanced: median age 49 yrs (23–81). Stage IVB: 5%; recurrent 62%; persistent 34%. 86% had prior radiotherapy (45% with chemotherapy); 42% had prior chemotherapy for recurrent/persistent disease. P improved PFS (HR = 0.66; 90% CI 0.48, 0.91 p = 0.013) and OS (HR = 0.67; 90% CI 0.46, 0.99 p = 0.045; median OS for P is 50.7 wks; L is 39.1 wks) with RR for P of 9% and L 5%. Most common AEs (%) P/L were diarrhea (54/58), nausea (36/33), anorexia (28/32), vomiting (20/24); the most common Gr 3 AE was diarrhea (11/13); Gr 4 for any individual AE was 1%; 1 Gr 5 event of cachexia unrelated to L. Conclusions: PFS and OS were significantly prolonged with P compared to L. P and L both demonstrated a favorable toxicity profile in pts with advanced and recurrent CC. This study demonstrates the potential benefit of P in CC. Further exploration is indicated.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Asian Cervical Cancer Prevention Advisory Board Eli Lilly, GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline

Abstract presentation from the 2009 ASCO Annual Meeting