KRAS mutational status assessment in patients with metastatic colorectal cancer: are the clinical implications so clear?

HEBBAR M., FOURNIER P. & ROMANO O. (2010) European Journal of Cancer Care 19 , 145–166
KRAS mutational status assessment in patients with metastatic colorectal cancer: are the clinical implications so clear? The CRYSTAL study demonstrated an advantage in terms of objective response and progression‐free survival for the FOLFIRI–cetuximab combination compared with first‐line FOLFIRI for patients with metastatic colorectal cancer. The results of an ancillary biological study with screening for a KRAS gene mutation in 540 patients were reported at the 2008 American Society of Clinical Oncology congress. The analysis confirmed the value of adding cetuximab only in the absence of KRAS mutation. These results led to recommend restriction of the use of cetuximab in Europe to patients with a tumour bearing wild‐type KRAS. How should this apparent simplification be integrated into clinical practice? The FOLFIRI–cetuximab combination is certainly a useful supplementary first‐line option although its place in relation to other high‐dose regimens (high‐dose FOLFIRI, FOLFOXIRI or FOLFOX‐7), conventional chemotherapy plus bevacizumab, or even a fluoropyrimidine alone in the case of unresectable metastases, has yet to be specified. For subsequent lines, no study has prospectively assessed the value of the chemotherapy–anti‐epidermal growth factor receptor combination as a function of KRAS status. Should the absence of objective response constantly observed in retrospective analyses in patients with a tumour presenting a KRAS mutation definitively exclude these patients while stable disease (and potentially a slight gain in survival) may be obtained?     

Improving outcomes in colorectal cancer: Where do we go from here?

Colorectal cancer (CRC) places a considerable burden on individuals and society in Europe, being the second most common cause of cancer-related death in the region. While earlier diagnosis and advances in treatment have considerably improved survival in recent years, further progress is needed. One of the greatest challenges associated with the treatment of CRC is the fact that current therapies for advanced disease are not curative, necessitating treatment for many years and placing a significant healthcare burden on society. To reduce the burden of CRC, care delivery must be more efficient and cost-effective. In particular, development of adequate screening programmes is needed, along with chemo-preventative strategies and newer, more active therapies. Further challenges include the lack of optimal selection of patients for adjuvant therapy, identification of the most appropriate target populations for current treatments and the optimum sequence for new molecular targeted agents. This article outlines current developments and unmet needs in CRC, and provides a detailed vision for improvements in the management of the disease. Implementation of some of these strategies will go some way to improving outcomes for patients with CRC.     

Early detection of pancreatic cancer: Where are we now and where are we going?

Pancreatic cancer (PC) is one of the most lethal malignancies. Recent studies indicate that patients with incidentally diagnosed PC have better prognosis than those with symptoms and that there is a sufficient window for early detection. However, effective early diagnosis remains difficult and depends mainly on imaging modalities and the development of screening methodologies with highly sensitive and specific biomarkers. This review summarizes recent advances in effective screening for early diagnosis of PC using imaging modalities and novel molecular biomarkers discovered from various “omics” studies including genomics, epigenomics, non‐coding RNA, metabonomics, liquid biopsy (CTC, ctDNA and exosomes) and microbiomes, and their use in body fluids (feces, urine and saliva). Although many biomarkers for early detection of PC have been discovered through various methods, larger scale and rigorous validation is required before their application in the clinic. In addition, more effective and specific biomarkers of PC are urgently needed.     

Capecitabine versus 5-fluorouracil in colorectal cancer: where are we now?

Fluorouracil (5-FU) remains the most widely used agent for colorectal cancer. Capecitabine is a rationally designed 5-FU pro-drug developed to mimic the continuous infusion of 5-FU while avoiding complications and inconvenience of intravenous administration. Capecitabine is absorbed intact from the gastrointestinal tract, converted enzymatically to active 5-FU, and released directly into the tumor. Capecitabine’s efficacy and safety are shown in multiple phase III trials across different disease stages and therapy lines. Three randomized phase III trials demonstrated the equivalence of capecitabine plus oxaliplatin (XELOX) versus 5-FU/leucovorin (LV)/oxaliplatin (FOLFOX). The safety of capecitabine compared with 5-FU depends on the regimen of 5-FU used. The adverse event rate with oxaliplatin in combination with infusional 5-FU is similar to that of capecitabine plus oxaliplatin but is associated with more neutropenia and venous thrombotic events; capecitabine plus oxaliplatin-based regimens tend to be associated with more grade 3 diarrhea and hand-foot skin reaction. Combination therapy with capecitabine and irinotecan (CapeIRI) versus 5-FU/LV and irinotecan (FOLFIRI) had more variable results; some former schedules resulted in excessive treatment-related toxicity. More recent data show that lower capecitabine and irinotecan doses, different schedules, and combination with targeted agents (e.g, bevacizumab) have resulted in more favorable outcomes.     

Adjuvant treatment in non-small cell lung cancer: Where are we now?

Lung cancer is the most common cancer worldwide, accounting for 1.2 million new cases annually. Despite aggressive local management of patients diagnosed with early-stage disease (stages I-IIIA), more than half of patients who have undergone surgical resection will die from complications caused by recurrent lung cancer. Over the past 5 years, results from several large trials assessing the use of adjuvant platinum-based chemotherapy in non-small cell lung cancer have become available. This article reviews the data from the most prominent of these trials and focuses on how the combination of cisplatin and etoposide has been evaluated for use in the adjuvant setting. Cisplatin-based therapy has now been shown to provide a significant survival benefit in several trials and recent meta-analyses. These data have changed the paradigm for how early-stage lung cancer is managed.     

Ethnicity and breast cancer in the UK: Where are we now?

Outcomes from breast cancer for women in the UK have improved significantly over recent decades. These gains are largely attributable to a combination of earlier diagnosis and access to treatments delivered to patients by the National Health Service irrespective of cost. Ethnic minority groups make up almost fifteen percent of the UK population and there is concern however that these groups may have poorer outcomes from the disease. In this short report we seek to summarise what the current evidence tells us about the patterns of breast cancer incidence and outcomes in ethnic minority women in the UK in order to raise awareness about this topic and provide consideration for what future research is needed to address the gaps that may exist.     

Epigenetics in radiotherapy: Where are we heading?

Radiotherapy is an important component of anti-cancer treatment. However, not all cancer patients respond to radiotherapy, and with current knowledge clinicians are unable to predict which patients are at high risk of recurrence after radiotherapy. There is therefore an urgent need for biomarkers to guide clinical decision-making.     

Cervical cancer burden in Latin America and the Caribbean: Where are we?

In May 2018, the World Health Organization (WHO) called for the elimination of cervical cancer. To monitor this initiative, we examined cervical cancer incidence and mortality in the Latin America and Caribbean (LAC) region using GLOBOCAN 2018, Cancer Incidence in Five Continents Series, and the WHO Mortality Database. We estimated the number of cases and age-standardized rates (ASRs) for cervical cancer incidence and mortality for 2018. We also presented the ASRs for recorded cervical cancer incidence from the period 2008 to 2012. We calculated annual rates and analyzed trends in cervical cancer incidence and mortality for all ages combined and for the following age groups: 0–29, 30–49, 50–64 and 65+. Finally, we calculated the estimated average annual percentage change in incidence and mortality rates for the past 10 years. In 2018, an estimated 56,000 new cervical cancer cases and 28,000 cervical cancer deaths occurred among women in LAC with great variations between subregions and countries/territories. Overall, trends in cervical cancer incidence and mortality have decreased over the past decade; however, the rates are still above the elimination threshold of 4 per 100,000 in most LAC countries/territories. Despite the encouraging trends observed, achieving the elimination of cervical cancer in the region still requests substantial political commitment and economic effort. Population-based cancer registries are critical in monitoring the elimination initiative.