Perioperative chemotherapy with or without epidermal growth factor receptor blockade in unselected patients with locally advanced oesophagogastric adenocarcinoma: Randomized phase II study with advanced biomarker program of the German Cancer Society (AIO/CAO STO-0801).

BACKGROUND: Perioperative chemotherapy significantly improves survival in patients with locally advanced oesophagogastric cancer (EGC). However, as approximately 60% of patients will die from their disease, new therapeutic agents such as molecular-targeted drugs are needed. PATIENTS AND METHODS: To evaluate the role of panitumumab with perioperative chemotherapy, previously untreated patients with locally advanced EGC received, in an open-label randomised phase II study (NEOPECX), standard epirubicin, cisplatin, capecitabine (ECX) chemotherapy with or without panitumumab. The primary end-point was the histological response rate after neoadjuvant therapy. The expression status and gene copy number of EGFR, HER2, and MET were determined by immunohistochemistry and fluorescence in situ hybridization (FISH). Plasma samples were collected before the first cycle of neoadjuvant chemotherapy. RESULTS: Overall, 160 patients (80 versus 80) were eligible. The majority (82% versus 80%) showed lymph node involvement. Rate of R0-resection, percentage of patients with downstaging to ypT0-2 at pathohistological evaluation, and rate of major histological response was equal in both arms. Toxicity was increased by panitumumab with regard to thromboembolic events and skin toxicity. Patients with tumour EGFR, HER2 or MET expression had shorter progression-free and overall survival. FISH positivity for these markers was associated with shorter survival independent of therapy. High levels of soluble EGFR in particular predicted poor survival in the panitumumab arm. CONCLUSION: The addition of panitumumab to ECX did not improve downstaging of locally advanced EGC. Low plasma levels of pathway-associated proteins such as sEGFR may identify a group of patients that benefit from EGFR-directed therapy. CLINICALTRIALS.GOV: NCT01234324.

Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): Long-term results of a controlled randomised trial.

BACKGROUND: Results of the PreOperative therapy in Esophagogastric adenocarcinoma Trial (POET) showed some benefits when including radiotherapy into the preoperative treatment. This article is reporting long-term results of this phase III study. PATIENTS AND METHODS: Patients with locally advanced adenocarcinomas of the oesophagogastric junction (Siewert types I-III) were eligible. Randomisation was done to chemotherapy (group A) or induction chemotherapy and chemoradiotherapy (CRT; group B) followed by surgery. RESULTS: The primary end-point of the study was overall survival at 3 years. The study was closed early after 119 patients having been randomised and were eligible. Local progression-free survival after tumour resection was significantly improved by CRT (hazard ratio [HR] 0.37; 0.16-0.85, p = value 0.01) and 20 versus 12 patients were free of local tumour progression at 5 years (p = 0.03). Although the rate of postoperative in-hospital mortality was somewhat higher with CRT (10.2% versus 3.8%, p = 0.26), more patients were alive at 3 and 5 years after CRT (46.7% and 39.5%) compared with chemotherapy (26.1% and 24.4%). Thus, overall survival showed a trend in favour of preoperative CRT (HR 0.65, 95% confidence interval [CI] 0.42-1.01, p = 0.055). CONCLUSION: Although the primary end-point overall survival of the study was not met, our long-term follow-up data suggest a benefit in local progression-free survival when radiotherapy was added to preoperative chemotherapy in patients with locally advanced adenocarcinoma of the oesophagogastric junction.

Autotransplant with and without induction chemotherapy in older multiple myeloma patients: long-term outcome of a randomized trial.

Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction. For all patients, double autologous transplantation after melphalan 140 mg/m2 (MEL140) was planned. The primary end point was progression-free survival. Of 420 eligible patients, 85% received a first transplant and 69% completed double transplantation. Treatment duration was short with a median of 7.7 months with induction chemotherapy cycles and 4.6 months without induction. On an intention-to-treat basis, median progression-free survival with induction chemotherapy cycles (207 patients) was 21.4 months versus 20.0 months with no induction cycles (213 patients) (hazard ratio 1.04, 95% confidence interval 0.84-1.28; P=0.36). Per protocol, progression-free survival was 23.7 months versus 23.0 months (P=0.28). Patients aged 65 years or over (55%) did not have an inferior outcome. Patients with low-risk cytogenetics [absence of del17p13, t(4;14) and 1q21 gains] showed a favorable overall survival and included the patients with sustained first remission. MEL140 was associated with a low rate of severe mucositis (10%) and treatment-related deaths (1%). Based on hazard ratio, the short treatment arm consisting of mobilization chemotherapy and tandem MEL140 achieved 96% of the progression-free survival, demonstrating its value as an independent component of therapy in older patients with multiple myeloma who are considered fit for autologous transplantation. (clinicaltrials.gov identifier: 02288741).

Bone pain reduction in patients with metastatic breast cancer treated with ibandronate-results from a post-marketing surveillance study.

BACKGROUND: Pain relief is an important treatment goal for breast cancer patients with metastatic bone disease and treatment should be associated with a low rate of side effects. This interim analysis of a prospective non-interventional study documents the efficacy and safety of the amino-bisphosphonate ibandronate in the treatment of metastatic bone disease under real-life conditions. PATIENTS AND METHODS: For up to 24 weeks 913 breast cancer patients received IV infusions of 6 mg ibandronate every 3-4 weeks or 50 mg of oral ibandronate once daily. Efficacy variables included pain severity, analgesic use, and skeletal-related events; the major safety parameter was renal function, assessed by serum creatinine levels. Subgroup analyses were performed according to pretreatment with bisphosphonates (none, ibandronate, or other bisphosphonates). RESULTS: At baseline, patients with ibandronate pretreatment tended to have lower mean pain scores and lower serum creatinine levels than those pre-treated with other bisphosphonates. Over the observation period, analgesic use did not increase. Among the 712 patients reporting pain at baseline, 70% achieved an improvement in pain severity during treatment with ibandronate, and there was no evidence to suggest relevant differences in mean pain reductions with IV or oral administration of ibandronate or according to prior bisphosphonate treatment. Skeletal-related events were rare (7%). Changes in serum creatinine levels during ibandronate treatment were small and both formulations of ibandronate were rated as well tolerated by physicians and patients. CONCLUSIONS: Data from this non-interventional study confirm the analgesic efficacy and safety profile of IV and oral ibandronate under real-life conditions.