ESMO @ ECC 2013: Cediranib Shows Benefit in Women with Relapsed, Platinum-Sensitive Ovarian Cancer (ICON6)

Overall patient benefit was demonstrated bycediranib, a novel vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI).

Phase III trial results showed that the addition of cediranib to chemotherapy increased progression-free survival by about three months in women with recurrent platinum-sensitive ovarian cancer. Additional benefit was obtained when cediranib was used as maintenance therapy, increasing overall- and progression-free survival over chemotherapy alone.

Dr. Jonathan Ledermann of the University College London (UCL) Cancer Institute, Cancer Research UK & UCL Trials Centre, London, UK presented findings on 30 September during the Best and Late Breaking Abstracts segment of Presidential Session III (Abstract E17-7020) at the 17th ECCO – 38th ESMO – 32nd ESTRO European Cancer Congress in Amsterdam, The Netherlands. The Congress was held from the 27 September through the 1 October, 2013 and was part of a series of European Cancer Congresses that are organised in joint partnership with ESSO, EACR, EONS and SIOPE to offer multidisciplinary and multi-professional educational opportunities in oncology.

Ground-breaking results of VEGFR inhibition in relapsed, platinum-sensitive ovarian cancer

Cediranib is a potent oral inhibitor of VEGFR-1,-2,-3 that halts VEGF signaling and has shown favourable activity when administered alone in ovarian cancer, leading investigators to test whether the addition of cediranib could improve the results achieved by chemotherapy and could be used as maintenance therapy to further improve outcome in patients with platinum-sensitive ovarian cancer in first relapse.

ICON6 is an international three-arm, double-blind placebo-controlled, randomised, phase III trial that enrolled 456 patients from 63 centres who were then randomised 2:3:3 to one of three cohorts: platinum-based chemotherapy with placebo maintenance (reference), concurrent cediranib at 20mg/day during chemotherapy followed by placebo for up to 18 months (concurrent), or cediranib 20mg/day followed by maintenance cediranib (concurrent + maintenance). Chemotherapy consisted on up to six cycles of platinum/paclitaxel, carboplatin/cisplatin alone, or platinum/gemcitabine. The study primary endpoint was progression-free survival (PFS) in the reference arm as compared to the concurrent + maintenance arms. Secondary endpoints were overall survival (OS), toxicity and quality of life. Survival time was estimated using restricted means (RM) estimates.

The patients’ median age was 62 years, and their ECOG performance status was 0/1. The interval from previous treatment was more than 12 months in 67% of patients. These baseline characteristics were balanced between the three arms.

Patients benefit was demonstrated in the cediranib maintenance arm over sole chemotherapy with time to progression, OS and PFS all extended by several months.

The RM estimates showed an increased time to progression of 3.2 months during 2 years, from 9.4 with chemotherapy to 12.6 for the cediranib/chemotherapy arm.

Similarly using RM to estimate the effect of maintenance therapy with cediranib, OS increased by 2.7 months from 17.6 to 20.3 in the concurrent + maintenance cediranib arm over the reference arm, respectively (hazard ratio [HR] 0.70; log-rank test  p = 0.0419). RM for the reference versus the concurrent + maintenance arm demonstrated  an increase in PFS of 2.0 months, from 9.4 to 11.4 months, respectively (HR 0.68; p = 0.0022).

Significantly more adverse events occurred in the cediranib-maintenance arm, including hypertension, diarrhoea, hypothyroidism, hoarseness, haemorrhage, proteinuria and fatigue.

The authors commented that this was the first time an overall survival benefit has been seen with a VEGFR TKI in recurrent ovarian cancer. Furthermore, that cediranib given concurrently with platinum-based chemotherapy improved progression-free survival and significantly improved both progression-free and overall survival when continued as maintenance in women with recurrent ovarian cancer.

The authors declared no conflict of interest.