Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.

In this prospective phase III trial, afatinib combined with paclitaxel improved progression-free survival and objective response, compared with single-agent chemotherapy, in patients with NSCLC who were clinically enriched for ErbB dependency having failed platinum-based chemotherapy, gefitinib/erlotinib and afatinib monotherapy after initial benefit on each tyrosine kinase inhibitor.

Supplemental digital content is available in the text.

Addition of lapatinib to chemoradiotherapy and its use as long-term maintenance therapy does not offer any efficacy benefits and had additional toxicity compared with placebo in patients with surgically treated high-risk SCCHN.

No abstract

AimsCachexia, the wasting disorder associated with a wide range of serious illnesses including cancer, is a major cause of morbidity and mortality. There is currently no widely approved therapeutic agent for treating or preventing cancer-associated cachexia. Colorectal cancer and non-small cell lung cancer have relatively high incidences of cachexia, approximately 28% and 34%, respectively. Neurohormonal overactivity has been implicated in the genesis and progression of cachexia and beta receptor antagonism has been proposed as a potential therapy. MT-102, a novel anabolic/catabolic transforming agent, has a multi-functional effect upon three potential pharmacological targets in cancer cachexia, namely reduced catabolism through non-selective β-blockade, reduced fatigue, and thermogenesis through central 5-HT1a antagonism and increased anabolism through partial β-2 receptor agonism.MethodsAt least 132 male and female patients, aged between 25 and 80 years with a confirmed diagnosis of late-stage non-small cell lung cancer or colorectal cancer, with cachexia will be randomised to either one of the two MT-102 doses or placebo in a 3:1:2 ratio (MT-102 10 mg BD−1/MT-102 2.5 mg BD/placebo). Patients will continue on study treatment for maximally 16 weeks. The primary endpoint, to be analysed by assigned treatment group, will be body weight change over 16 weeks. For this endpoint, the study has 85% power (0.05% significance level) to detect per 4-week period a mean change of −0.8 kg in the placebo group and 0 kg in the high-dose MT-102 arm. The first patient was randomised in February 2011 and patient recruitment is expected to continue until mid-2012.PerspectiveThe ACT-ONE trial is designed to test whether the anabolic/catabolic transforming agent MT-102 will positively impact on the rate of change of body weight in cancer cachexia, thereby evaluating a novel therapeutic strategy in this hitherto poorly treatable condition. A separate ACT-TWO trial will recruit patients who complete the ACT-ONE trial and remain on randomised double-blind medication. Participants in ACT-TWO will be followed for an additional period with a separate primary endpoint.

Introduction: SOR is a targeted therapeutic agent indicated for advanced renal cell carcinoma and hepatocellular carcinoma. SOR targets multiple kinases involved in tumor growth and angiogenesis. The TIES (Trials to Investigate the Effects of Sorafenib in BC) program includes 4 phase 2b randomized, double-blind, placebo-controlled screening trials in HER2-negative BC. Recently, the first of these trials, SOR+capecitabine (CAP) vs placebo (PL)+CAP demonstrated a significant progression-free survival (PFS) benefit in pts with advanced BC. Here we present initial results from the second of the 4 trials. This study evaluated the efficacy and safety of SOR in combination with PAC as a first-line regimen for pts with advanced BC.Methods: Pts with HER2-negative, locally recurrent or metastatic BC were eligible for first-line treatment for advanced BC. Previous cytotoxic (non-metastatic), endocrine, or radiation therapy was allowed. Pts were randomized 1:1 (stratified by visceral vs non-visceral metastatic disease) to SOR (400 mg, orally, twice daily, continuously) or PL in combination with PAC (90 mg/m2 weekly, IV, 3 weeks on/1 week off). The primary endpoint was PFS. Secondary endpoints included overall survival (OS), time to progression (TTP), overall response rate (ORR), and safety. A sample size of 220 pts was planned to detect a targeted HR of 0.65 (90% power and 1-sided a=0.14). The study is registered at ClinicalTrials.gov (NCT00499525).Results: From January 2008 to January 2009, 237 pts were randomized to SOR+PAC (n=119) vs PL+PAC (n=118), with 170 pts in India (74% vs 69%), 52 pts in the United States (21% vs 23%), and 15 pts in Brazil (5% vs 8%). Treatment groups were balanced for age (mean, 51.9 y), ECOG performance 0 (45%) and 1 (53%), stage IV disease (85%), visceral metastatic disease (75%), and previous non-metastatic chemo (58%). Results of the study were as follows for SOR+PAC vs PL+PAC: median PFS 6.9 vs 5.6 mos (HR 0.788; 95% CI, 0.558-1.112; 1-sided log rank P=0.0857), median TTP 8.1 vs 5.6 mo (HR 0.674; 95% CI, 0.465-0.975; 1-sided log rank P=0.0171), and ORR of 67% vs 54% (1-sided Cochran-Mantel-Haenszel P=0.0234). OS data are pending. Discontinuation of study treatment due to adverse events occurred in 23 pts (19%) in the SOR+PAC vs 5 pts (4%) in the PL+PAC. Grade 3/4 toxicities (SOR+PAC vs PL+PAC) included hand-foot skin reaction (30% vs 3%), asthenia (7% vs 3%), peripheral neuropathy (6% vs 7%), neutropenia (13% vs 7%), and anemia (11% vs 6%). Treatment-related deaths occurred in 2 pts (malaria and liver dysfunction), both in the SOR+PAC arm.Conclusions: Results of the primary endpoint, PFS, demonstrated a trend favoring SOR+PAC over PL+PAC in the treatment of advanced BC (HR 0.788; P=0.0857). In addition, significant improvements in TTP and ORR were observed. OS data are pending. There were no new toxicities observed with the combination and AEs were manageable. These data indicate that SOR provides added benefit when combined with PAC compared with single-agent PAC in the first-line treatment of advanced BC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 44.

Therapy was safe. The responses, time to treatment progression and survival are encouraging for patients with aggressive refractory disease.