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Background: KRAS mutation status is a candidate marker for predicting survival in patients with metastatic colorectal cancer (mCRC) treated with cetuximab (CTX). Patients and methods:We studied the KRAS mutation status of 113 patients with irinotecan refractory mCRC treated with CTX in clinical trials. A predictive model for objective response (OR), progression-free survival (PFS) and overall survival (OS) was constructed using logistic and Cox regression.Results: OR was seen in 27 of 66 KRAS wild-type (WT) patients versus 0 of 42 in KRAS mutants. Median OS was significantly better in KRAS WT versus mutants (43.0 versus 27.3 weeks; P = 0.020). Decrease in tumor sizes was significantly larger at all time points in WT patients. KRAS WT patients with an initial relative decrease of tumor size >9.66% at week 6 had a significantly better median OS compared with all other patients (74.9 versus 30.6 weeks; P = 0.0000025). Within KRAS WT patients OS was significantly better in patients with an initial decrease compared with those without [median OS: 74.9 versus 30.6 weeks (P = 0.00000012)].Conclusions: KRAS WT status is associated to survival benefit in CTX treated mCRC. This benefit is even more pronounced in those patients with early radiological response. These characteristics may be exploited for response prediction.Key words: cetuximab, colorectal cancer, EGFR, KRAS, survival introduction A recent advance in oncology is the targeting of the epidermal growth factor receptor (EGFR) in the treatment of many tumor types. Cetuximab (CTX) (ErbituxÒ, Merck KGaA, Darmstadt, Germany) is a chimeric immunoglobulin G1 monoclonal antibody which binds the EGFR with high affinity and competitively inhibits ligand binding [1]. This prevents activation of downstream signalling pathways such as the PI3K/ Akt, RAS/Erk and STAT pathways, resulting in the inhibition of cellular proliferation and in the induction of apoptosis. However, for many tumor types including metastatic colorectal cancer (mCRC), it is not clear what proportion of tumors are dependent on EGFR signalling for their survival, nor how additional molecular alterations present in the tumor may influence primary or secondary resistance to EGFR inhibitors. CTX is approved for irinotecan-resistant mCRC expressing EGFR by immunohistochemistry (IHC). Response rates in this group however only amount to 23% in combination with chemotherapy and about 10% in monotherapy [2,3]. Increased response rates in the combination arm did not translate into increased survival. As yet no clinical or molecular markers are available to identify those patients with a longer overall survival (OS). Predictive markers of response and survival benefit after CTX are urgently required to allow the rational and effective use of these drugs.In a small series, Lièvre et al. [4] have shown objective response (OR) to CTX to be excluded in KRAS-mutated CRC and most importantly, showed an increase in OS for the KRAS wild-type (WT) patients. We retrospectively studied the ability of KRAS mutations and tumo...

The OS benefit of oxaliplatin-based adjuvant chemotherapy, increasing over time and with the disease severity, was confirmed at 10 years in patients with stage II to III colon cancer. These updated results support the use of FOLFOX in patients with stage III disease, including those with dMMR or BRAF mutation.

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Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy with an extremely poor prognosis, as shown by a 1-year survival rate of around 18% for all stages of the disease. The low survival rates associated with PDAC primarily reflect the fact that tumours progress rapidly with few specific symptoms and are thus at an advanced stage at diagnosis in most patients. As a result, there is an urgent need to develop accurate markers of pre-invasive pancreatic neoplasms in order to facilitate prediction of cancer risk and to help diagnose the disease at an earlier stage. However, screening for early diagnosis of prostate cancer remains challenging and identifying a highly accurate, low-cost screening test for early PDAC for use in clinical practice remains an important unmet need. More effective therapies are also crucial in PDAC, since progress in identifying novel therapies has been hampered by the genetic complexity of the disease and treatment remains a major challenge. Presently, the greatest step towards improved treatment efficacy has been made in the field of palliative chemotherapy by introducing FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin) and gemcitabine/nab-paclitaxel. Strategies designed to raise the profile of PDAC in research and clinical practice are a further requirement in order to ensure the best treatment for patients. This article proposes a number of approaches that may help to accelerate progress in treating patients with PDAC, which, in turn, may be expected to improve the quality of life and survival for those suffering from this devastating disease.