Salah-Eddin Al-Batran

Bio: Salah-Eddin Al-Batran is an academic researcher from Heidelberg University. The author has contributed to research in topics: Cancer & Oxaliplatin. The author has an hindex of 45, co-authored 238 publications receiving 11799 citations.

FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial

Abstract: Summary Background Cetuximab and bevacizumab have both been shown to improve outcomes in patients with metastatic colorectal cancer when added to chemotherapy regimens; however, their comparative effectiveness when partnered with first-line fluorouracil, folinic acid, and irinotecan (FOLFIRI) is unknown. We aimed to compare these agents in patients with KRAS (exon 2) codon 12/13 wild-type metastatic colorectal cancer. Methods In this open-label, randomised, phase 3 trial, we recruited patients aged 18–75 years with stage IV, histologically confirmed colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, an estimated life expectancy of greater than 3 months, and adequate organ function, from centres in Germany and Austria. Patients were centrally randomised by fax (1:1) to FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab (using permuted blocks of randomly varying size), stratified according to ECOG performance status, number of metastatic sites, white blood cell count, and alkaline phosphatase concentration. The primary endpoint was objective response analysed by intention to treat. The study has completed recruitment, but follow-up of participants is ongoing. The trial is registered with ClinicalTrials.gov, number NCT00433927. Findings Between Jan 23, 2007, and Sept 19, 2012, 592 patients with KRAS exon 2 wild-type tumours were randomly assigned and received treatment (297 in the FOLFIRI plus cetuximab group and 295 in the FOLFIRI plus bevacizumab group). 184 (62·0%, 95% CI 56·2–67·5) patients in the cetuximab group achieved an objective response compared with 171 (58·0%, 52·1–63·7) in the bevacizumab group (odds ratio 1·18, 95% CI 0·85–1·64; p=0·18). Median progression-free survival was 10·0 months (95% CI 8·8–10·8) in the cetuximab group and 10·3 months (9·8–11·3) in the bevacizumab group (hazard ratio [HR] 1·06, 95% CI 0·88–1·26; p=0·55); however, median overall survival was 28·7 months (95% CI 24·0–36·6) in the cetuximab group compared with 25·0 months (22·7–27·6) in the bevacizumab group (HR 0·77, 95% CI 0·62–0·96; p=0·017). Safety profiles were consistent with the known side-effects of the study drugs. The most common grade 3 or worse adverse events in both treatment groups were haematotoxicity (73 [25%] of 297 patients in the cetuximab group vs 62 [21%] of 295 patients in the bevacizumab group), skin reactions (77 [26%] vs six [2%]), and diarrhoea (34 [11%] vs 40 [14%]). Interpretation Although the proportion of patients who achieved an objective response did not significantly differ between the FOLFIRI plus cetuximab and FOLFIRI plus bevacizumab groups, the association with longer overall survival suggests that FOLFIRI plus cetuximab could be the preferred first-line regimen for patients with KRAS exon 2 wild-type metastatic colorectal cancer. Funding Merck KGaA.

One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial.

Abstract: Context Adjuvant imatinib administered for 12 months after surgery has improved recurrence-free survival (RFS) of patients with operable gastrointestinal stromal tumor (GIST) compared with placebo. Objective To investigate the role of imatinib administration duration as adjuvant treatment of patients who have a high estimated risk for GIST recurrence after surgery. Design, Setting, and Patients Patients with KIT-positive GIST removed at surgery were entered between February 2004 and September 2008 to this randomized, open-label phase 3 study conducted in 24 hospitals in Finland, Germany, Norway, and Sweden. The risk of GIST recurrence was estimated using the modified National Institutes of Health Consensus Criteria. Intervention Imatinib, 400 mg per day, orally for either 12 months or 36 months, started within 12 weeks of surgery. Main Outcome Measures The primary end point was RFS; the secondary end points included overall survival and treatment safety. Results Two hundred patients were allocated to each group. The median follow-up time after randomization was 54 months in December 2010. Diagnosis of GIST was confirmed in 382 of 397 patients (96%) in the intention-to-treat population at a central pathology review. KIT or PDGFRA mutation was detected in 333 of 366 tumors (91%) available for testing. Patients assigned for 36 months of imatinib had longer RFS compared with those assigned for 12 months (hazard ratio [HR], 0.46; 95% CI, 0.32-0.65; P Conclusion Compared with 12 months of adjuvant imatinib, 36 months of imatinib improved RFS and overall survival of GIST patients with a high risk of GIST recurrence. Trial Registration clinicaltrials.gov Identifier: NCT00116935

Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer

Abstract: Background A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer. Methods We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival. Results ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P = 0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001). Conclusions In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival. (Current Controlled Trials number, ISRCTN93793971.)

Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations

Abstract: Purpose The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS). Patients and Methods In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs). Results A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatmentrelated adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain. Conclusion Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.