SummaryBackgroundTherapeutic antibodies targeting EGFR have activity in advanced colorectal cancer, but results from clinical trials are inconsistent and the population in which most benefit is derived is uncertain. Our aim was to assess the addition of panitumumab to irinotecan in pretreated advanced colorectal cancer.MethodsIn this open-label, randomised trial, we enrolled patients who had advanced colorectal cancer progressing after fluoropyrimidine treatment with or without oxaliplatin from 60 centres in the UK. From December, 2006 until June, 2008, molecularly unselected patients were recruited to a three-arm design including irinotecan (control), irinotecan plus ciclosporin, and irinotecan plus panitumumab (IrPan) groups. From June 10, 2008, in response to new data, the trial was amended to a prospectively stratified design, restricting panitumumab randomisation to patients with KRAS wild-type tumours; the results of the comparison between the irinotcan and IrPan groups are reported here. We used a computer-generated randomisation sequence (stratified by previous EGFR targeted therapy and then minimised by centre, WHO performance status, previous oxaliplatin, previous bevacizumab, previous dose modifications, and best previous response) to randomly allocate patients to either irinotecan or IrPan. Patients in both groups received 350 mg/m2 intravenous irinotecan every 3 weeks (300 mg/m2 if aged ≥70 years or a performance status of 2); patients in the IrPan group also received intravenous panitumumab 9 mg/kg every 3 weeks. The primary endpoint was overall survival in KRAS wild-type patients who had not received previous EGFR targeted therapy, analysed by intention to treat. Tumour DNA was pyrosequenced for KRASc.146, BRAF, NRAS, and PIK3CA mutations, and predefined molecular subgroups were analysed for interaction with the effect of panitumumab. This study is registered, number ISRCTN93248876.ResultsBetween Dec 4, 2006, and Aug 31, 2010, 1198 patients were enrolled, of whom 460 were included in the primary population of patients with KRASc.12–13,61 wild-type tumours and no previous EGFR targeted therapy. 230 patients were randomly allocated to irinotecan and 230 to IrPan. There was no difference in overall survival between groups (HR 1·01, 95% CI 0·83–1·23; p=0·91), but individuals in the IrPan group had longer progression-free survival (0·78, 0·64–0·95; p=0·015) and a greater number of responses (79 [34%] patients vs 27 [12%]; p<0·0001) than did individuals in the irinotecan group. Grade 3 or worse diarrhoea (64 [29%] of 219 patients vs 39 [18%] of 218 patients), skin toxicity (41 [19%] vs none), lethargy (45 [21]% vs 24 [11%]), infection (42 [19%] vs 22 [10%]) and haematological toxicity (48 [22%] vs 27 [12%]) were reported more commonly in the IrPan group than in the irinotecan group. We recorded five treatment-related deaths, two in the IrPan group and three in the irinotecan group.InterpretationAdding panitumumab to irinotecan did not improve the overall survival of patients with wild-type KRAS tumours. ...

The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.

• Changes in CT body composition occur after neoadjuvant chemotherapy in oesophageal cancer. • Sarcopenia was more prevalent after neoadjuvant chemotherapy. • Fat mass, fat-free mass and weight decreased after neoadjuvant chemotherapy. • Changes in body composition were associated with CRM positivity. • Changes in body composition did not affect perioperative complications and survival.

Background:Although comorbidities are identified in routine oncology practice, intervention plans for the coexisting needs of older people receiving chemotherapy are rarely made. This study evaluates the impact of geriatrician-delivered comprehensive geriatric assessment (CGA) interventions on chemotherapy toxicity and tolerance for older people with cancer.Methods:Comparative study of two cohorts of older patients (aged 70+ years) undergoing chemotherapy in a London Hospital. The observational control group (N=70, October 2010–July 2012) received standard oncology care. The intervention group (N=65, September 2011–February 2013) underwent risk stratification using a patient-completed screening questionnaire and high-risk patients received CGA. Impact of CGA interventions on chemotherapy tolerance outcomes and grade 3+ toxicity rate were evaluated. Outcomes were adjusted for age, comorbidity, metastatic disease and initial dose reductions.Results:Intervention participants undergoing CGA received mean of 6.2±2.6 (range 0–15) CGA intervention plans each. They were more likely to complete cancer treatment as planned (odds ratio (OR) 4.14 (95% CI: 1.50–11.42), P=0.006) and fewer required treatment modifications (OR 0.34 (95% CI: 0.16–0.73), P=0.006). Overall grade 3+ toxicity rate was 43.8% in the intervention group and 52.9% in the control (P=0.292).Conclusions:Geriatrician-led CGA interventions were associated with improved chemotherapy tolerance. Standard oncology care should shift towards modifying coexisting conditions to optimise chemotherapy outcomes for older people.