Abstract
Abstract only
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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.
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