Chemotherapy in ovarian cancer
The ICON7 study investigated whether adding bevacizumab to standard chemotherapy with carboplatin and paclitaxel delayed ovarian cancer progression. The study included 1,528 women with early and advanced ovarian cancer who were randomly assigned to either 6 cycles of carboplatin plus paclitaxel every 3 weeks, or carboplatin plus paclitaxel plus bevacizumab every 3 weeks followed by 36 weeks of observation in the first arm or a further 12 cycles of bevacizumab 7.5mg/kg.
The effect of adding bevacizumab to standard therapy varied and peaked at 12 months after randomisation, with 15% improvement in progression-free survival; the effect then reduced, resulting in an overall improvement in survival of 1.5 months. Long-term results will allow further evaluation.
Everolimus in neuroendocrine tumours
The results of RADIANT-2, a phase III study comparing everolimus plus octreotide acetate injectable suspension (octreotide LAR) with placebo plus octreotide LAR in patients with advanced neuroendocrine tumours, were presented at the 35th ESMO Congress. This randomised, double-blind, placebo-controlled international multicentre study enrolled 429 patients who were randomly assigned to 10mg oral everolimus or placebo plus octreotide LAR 30mg IM injection every 28 days.
The primary endpoint, progression-free survival, was not met. However, the combination of everolimus plus octreotide LAR extended time without tumour growth from 11.3 to 16.4 months. The combination treatment also reduced risk of disease progression by 40%. The most common adverse events with everolimus plus octreotide were stomatitis, rash, fatigue and diarrhoea.
EGFR tyrosine kinase inhibitors in NSCLC
EGFR mutation testing should be a standard part of the treatment pathway for patients with advanced non-small cell lung cancer (NSCLC) when selecting first-line treatment, according to researchers presenting overall survival results from the IPASS study.
The authors hypothesised that first-line therapy with an EGFR tyrosine kinase inhibitor (TKI) in selected patients would be as effective as first-line treatment with carboplatin or paclitaxel. The study included 1,217 chemo-naive NSCLC patients from East Asia, who were never- or ex-light smokers with adenocarcinoma histology. Study participants were randomly assigned to gefitinib or carboplatin plus paclitaxel. Overall survival rates were similar for both treatment arms. Patients with EGFR mutation-positive disease had better outcomes than those with EGFR-negative disease. Patients with a particular mutation in the EGFR gene had greater sensitivity to gefitinib and experienced dramatic and prolonged responses.
Erlotinib plus ARQ197 for advanced NSCLC
Final results from a randomised placebo-controlled phase II trial indicate that combining erlotinib with the c-MET inhibitor ARQ197 prolongs progression-free survival in EGFR-inhibitor naive patients with advanced NSCLC. The study included 167 patients with advanced NSCLC who had previously received chemotherapy but were EGFR-inhibitor naive. They were randomly assigned to erlotinib plus ARQ197 (n = 84) or erlotinib plus placebo (n = 83). The median progression-free survival was longer in patients treated with ARQ197, at 16.1 weeks compared with 9.7 weeks for those treated with placebo. Progression-free survival benefit was prominent in patients with non-squamous histology, KRAS mutations and EGFR-wild type status. androgen inhibition in prostate cancer.
Androgen inhibition in prostate cancer
Abiraterone acetate, an androgen inhibitor, can extend life in patients with metastatic prostate cancer, according to this phase III trial carried out by lead investigator Dr Johann de Bono and his team at the Institute of Cancer Research.
This randomised, placebo-controlled study included 1,195 patients from 13 countries with metastatic castration-resistant prostate cancer, who had previously been treated with docetaxel. Patients were randomly assigned to receive treatment with abiraterone acetate plus prednisone (n = 797) or prednisone plus placebo (n = 398). The median overall survival in the abiraterone arm was 14.8 months, compared with 10.9 months in the placebo arm. During interim analysis, the benefits of abiraterone were noted and it was made available to patients in the placebo arm. The most common adverse affects with abiraterone were fluid retention and hypokalaemia.
Therapy in metastatic colorectal cancer
The Nordic VII phase III study investigated the value of adding first-line anti-EGFR treatment with cetuximab to a 3-drug chemotherapy regimen in metastatic colorectal cancer (CRC).
Between May 2005 and October 2007, 566 patients from Scandinavia and Iceland with metastatic CRC were randomly assigned to a combination of 5-fluorouracil plus folinate plus oxaliplatin (Nordic FLOX), FLOX plus cetuximab until disease progression, or intermittent FLOX plus continuous cetuximab. The primary endpoint was progression-free survival.
The results showed that combining cetuximab with Nordic FLOX did not significantly improve response rate, progression-free survival or overall survival compared with FLOX alone, regardless of KRAS mutation. BRAF mutation (present in 12% of tumours) was a strong negative prognostic factor. These results do not support the use of cetuximab with an oxalipatin regimen in the first-line setting for metastatic CRC.