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www.thelancet.com/oncology Published online October 4, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70460-1 1

Published OnlineOctober 4, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70460-1

The European Cancer Congress 2013 (17th ECCO–38th ESMO–32nd ESTRO) meeting was held in Amsterdam, Netherlands, on Sept 27–Oct 1, 2013

European Cancer Congress 2013Trastuzumab-DM1The antibody–drug conjugate trast-uzumab-DM1 (T-DM1) improves progression-free survival (PFS) com-pared with standard of care for patients with heavily pretreated HER2-positive metastatic breast cancer, according to the primary results of the TH3RESA trial, presented by Hans Wildiers (Leuven, Belgium). Patients who had previously received two or more HER2-directed treatments were randomised to receive either T-DM1 (n=404) or treatment of physician’s choice (n=198). Median PFS was 3·3 months for women who received physician’s choice versus 6·2 months for those who received T-DM1 (hazard ratio [HR] 0·53, 95% CI 0·42–0·66; p<0·0001). An interim analysis of overall survival also suggested a benefi cial eff ect with T-DM1, although these data were very preliminary at the time of analysis. Fewer grade 3 or worse adverse events were reported with T-DM1 than with physician’s choice (32·3% of patients vs 43·5%).

TRINOVA-1 A number of trials have established that targeting angiogenesis is a valid option for patients with ovarian cancer; however, targeting the VEGF axis is often associated with adverse events such as hypertension, haemorrhage, and thromboembolism. Bradley Monk (Phoenix, AZ, USA) presented data from the TRINOVA-1 trial, which compared trebananib—a novel agent that targets angiogenesis by inhibiting the binding of angiopoietin 1 and 2 to the Tie2 receptor—plus paclitaxel with paclitaxel plus placebo for patients with recurrent ovarian cancer. Median PFS was 7·2 months (95% CI 5·8–7·4) in the trebananib group and 5.4 months (4·3–5·5) in the placebo group (HR 0·66, 95% CI 0·56–0·76; p<0·001). An interim analysis showed that median overall survival was 19·0 months in the experimental group and 17·3 months in the control group. Trebananib was

associated with a greater degree of localised oedema than was paclitaxel alone (64% of patients were aff ected in the trebananib group vs 28% in the placebo group), but adverse events generally associated with the class of anti-VEGF agents were not increased.

ASPECCTPanitumumab is non-inferior to cetuxi mab for previously treated patients with KRAS wild-type meta-static colorectal cancer, according to data presented by Timothy Price (Adelaide, Australia). In the ASPECCT trial, median overall survival was 10·4 months (95% CI 9·4–11·6) for patients in the panitumumab group (n=499) versus 10·0 months (9·3–11·0) for those in the cetuximab group (n=500; HR 0·97, 95% CI 9·3–11·0; p=0·0007). The conclusion of non-inferiority was reached in an analysis of retention rate, in which panitumumab was shown to retain 106% (95% CI 82–130) of the eff ect of cetuximab on overall survival seen in the NCIC CTG C0.17 study. Adverse events were as to be expected with each agent, and were much the same between groups, with the exception that there were fewer infusion-related reactions with panitumumab than with cetuximab.

GOLDRobert Motzer (New York, NY, USA) presented results of the phase 3 GOLD trial, in which patients who had progressed on at least one anti-VEGF agent and one mTOR inhibitor were randomly assigned to receive either dovitinib (n=284) or sorafenib (n=286). Neither PFS nor overall survival diff ered between groups: median PFS was 3·7 months with dovitinib and 3·6 months with sorafenib (HR 0·86, 95% CI 0·72–1·04; p=0·063) and median overall survival was 11·1 months with dovitinib and 11·0 months with sorafenib (HR 0·96, 95% CI 0·75–1·22; p=0·357).

Diarrhoea, nausea, and vomiting were more common with dovitinib than with sorafenib, and palmar-planter erythrodysesthesia, hypertension, and alopecia were more common with sorafenib. Although the study failed to show a benefi t with dovitinib, Motzer concluded that this was the first phase 3 trial to show that tyrosine-kinase inhibitors are active in patients who had previously progressed on VEGF and mTOR targeted therapies.

ICON6Jonathan Ledermann (London, UK) showed data from the ICON6 trial, which investigated the use of the anti-VEGF inhibitor cediranib for patients with platinum-sensitive ovarian cancer after fi rst relapse. 456 patients were randomly assigned in a 2:3:3 ratio to receive platinum-based chemotherapy and placebo, platinum-based chemo-therapy plus cediranib followed by placebo for 18 months (concurrent group), or the same regimen as in the second group with cediranib in place of placebo (maintenance group). Comparison of PFS in the control group with the concurrent and maintenance groups with a log-rank test showed a HR of 0·57 (95% CI 0·45–0·74; p=0·00001). However, non-propor-tional hazards were noted, rendering the HR difficult to interpret; to aid comparison, Ledermann presented restricted means estimates. Res-tricted means estimates of time to progression were 9·4 months in the control group and 12·6 months in the concurrent group. Similarly, an improvement in overall survival was also noted: overall survival was 17·6 months in the control group and 20·3 months in the concurrent group. As anticipated with agents targeting VEGF, cediranib was associated with increased hypertension, diarrhoea, hypothyroidism, haemorrhage, pro-teinuria, and fatigue.

Rob Brierley

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