Background Nilotinib inhibits the tyrosine kinase activity of ABL1/BCR-ABL1, as well as KIT, platelet-derived growth factor receptors (PDGFRs), and the discoidin domain receptor. Gain-of-function mutations in KIT or PDGFRα are key drivers in most gastrointestinal stromal tumours (GISTs). This trial was designed to test the efficacy and safety of nilotinib vs imatinib as first-line therapy for patients with advanced GISTs. Methods This randomised, open-label, multicentre phase 3 trial included 647 adult patients with previously untreated, histologically confirmed, metastatic and/or unresectable GISTs. Patients were stratified by prior adjuvant therapy and randomised in a 1:1 ratio to receive oral imatinib 400 mg once daily or oral nilotinib 400 mg twice daily. Centrally reviewed progression-free survival (PFS) was the primary endpoint. Response rates, toxicity, and overall survival were also analysed for the overall population and for mutation-defined subsets. Efficacy endpoints used the intention to treat principle. Here, the final results are reported. This trial is registered with ClinicalTrials.gov, number NCT00785785. Findings Because the futility boundary was crossed at a preplanned interim analysis, trial accrual terminated in April 2011. At final analysis of the core study (data cutoff, October 2012), PFS was higher with imatinib overall (hazard ratio [HR] 1.47) and in the KIT exon 9 subgroup (HR 32.46) but roughly similar between arms in the KIT exon 11 subgroup (HR 1.12). Sensitivity analyses suggested that informative censoring may have contributed, because of the high proportion of premature nilotinib progressions declared by local investigators and the design changes implemented following the interim analysis, potentially biasing PFS data in favour of the nilotinib arm. The most common adverse events were nausea, diarrhoea, and peripheral oedema in the imatinib arm and rash, nausea, and abdominal pain in the nilotinib arm. The most common serious adverse event in both arms was abdominal pain (imatinib, n=11 [3.5%]); nilotinib, n= 14 [4.4%]). Interpretation Our results suggest that nilotinib is not an optimal treatment approach for first-line GIST; however, future studies may identify patient subsets form whom first-line nilotinib could be of clinical benefit. Funding Novartis Pharmaceuticals.

Celecoxib can be used effectively and safely to prevent capecitabine-related HFS.

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases. Electronic supplementary material The online version of this article (10.1186/s13045-019-0702-0) contains supplementary material, which is available to authorized users.

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAF V600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAF V600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAF V600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population. What's new?The prevalence of Lynch syndrome (LS) varies significantly in different ethnic populations. In this study, the authors screened more than 3000 Chinese colorectal cancer patients for mutations associated with LS, including mismatch repair (MMR) and BRAF V600E mutations. They found that, while the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of mutations is different, including many not previously reported. Older patients had a decreased risk of LS, suggesting that germline sequencing may not be necessary in this population.