Reviews & Analysis

Preoperative 5-fluorouracil-based chemoradiation with optimal surgery provides very effective local control in locally advanced rectal cancer. Does adding oxaliplatin as a radiosensitizer provide any additional benefit? Is more always better?

Patients with colorectal cancer with mutated PIK3CA, identified from two large observational cohorts, had increased cancer-specific and overall survival if they used aspirin regularly after diagnosis compared to non-users. No effect of aspirin was seen in patients with wild-type PIK3CA. Mutated PIK3CA might be a useful biomarker to select patients who would benefit from adjuvant aspirin therapy.

A phase II trial comparing dual MAPK pathway inhibition by combining BRAF and MEK inhibitors with BRAF inhibition alone showed increased progression-free survival and reduced incidence of secondary malignancies in patients with mutant BRAF V600 melanoma. This trial provides strong support for developing combinations hitting the same pathway in melanoma.

The large randomized study by Crook et al. demonstrated that intermittent administration of androgen deprivation therapy should be considered the standard of care when patients with moderate and well-differentiated localized prostate cancer are treated for rising PSA levels after definitive radiotherapy.

The VELOUR and VITAL studies recently demonstrated ziv-aflibercept improved overall survival in patients with metastatic colorectal cancer (mCRC), including those previously treated with bevacizumab, but did not improve overall survival in non-small-cell lung cancer. Thus, VEGF-directed agents might be useful throughout the continuum of care in mCRC, but biomarkers are needed to identify patients likely to benefit.

An update of the COU-AA-301 study confirms a survival advantage with abiraterone–prednisone compared to prednisone in post-docetaxel patients with metastatic castration-resistant prostate cancer. We place these data in the context of earlier disease states and other novel agents and explore practical issues concerning the future use of abiraterone.

Addition of aprepitant, an NK-1 receptor antagonist, to dexamethasone and a 5-HT3 receptor antagonist contributes substantially to emetic control in patients receiving 5-day cisplatin-containing chemotherapy, a new trial shows. Some needs in antiemetic therapy remain unmet, including control of emesis with multiple-day chemotherapy and control of nausea.

A retrospective cohort study has shown that pancreatic radiation is a risk factor for diabetes in survivors of paediatric cancer. This validates and refines prior epidemiological observations of diabetes after radiation to the abdomen and total-body irradiation, and will result in modification of surveillance recommendations in national survivor guidelines.

Two novel agents targeting the androgen receptor signalling axis, even after chemotherapy treatment, have been demonstrated to be effective in patients with metastatic castration-resistant prostate cancer (CRPC). Enzalutamide is the newest approved treatment that improves survival in this lethal and morbid disease.

The observational registry CaPSURE study reported that men with prostate cancer who were taking aspirin were less likely to die of prostate cancer than nonusers. This favourable effect seems to be stronger than that observed in a pooled analysis of randomized clinical trials of aspirin, and in other observational studies.

Convincing data have shown that human papillomavirus (HPV)-DNA testing predicts the development of high-grade cervical cancer better than cytology. However, for HPV-positive women, triage with cytology testing should be performed before colposcopy. The question on how to proceed if the cytology test in HPV-positive women is negative remains unclear.

The 8-year European Study Group for Pancreatic Cancer has determined that adjuvant chemotherapy for periampullary neoplasms prolongs survival compared with surgery alone. Is now the time to implement social networks or other web-based applications to assist investigators and clinicians to find the optimal treatment faster?

Compared with anastrozole alone, the combination of fulvestrant and anastrozole significantly improved time without disease progression and extended the median overall survival of women with endocrine-responsive metastatic breast cancer; offering a new standard-of-care for these women. Unfortunately, information about the efficacy of the combination in the adjuvant setting is not available.

Dabrafenib is the second agent in the therapeutic class of selective BRAF inhibitors, and has proven efficacy in a phase III trial (BREAK-3) with impressive improvements in progression-free survival and response rates. Differences in the safety profile exist compared with vemurafenib, but the future lies in combinatorial strategies and improved patient selection.

The small EVEREST trial has shown that the concept of guiding cetuximab dose escalation using the clinical parameter of acneiform skin rash is safe. However, as no significant increase of cetuximab efficacy could be observed, data from the ongoing EVEREST II trial must be awaited before dose escalation can be considered for clinical use.

The Affordable Care Act—the Obama administration's signature legislation designed to insure over 30 million currently uninsured Americans—was recently declared constitutional by the US Supreme Court. Although not perfect, the law contains provisions that will benefit patients with cancer, those at risk of cancer and those in remission.

The current definition of multiple myeloma is outdated. The diagnosis requires evidence of overt end-organ damage, preventing initiation of early therapy when the malignancy is at its most susceptible stage. We propose an evidence-based approach using more-sensitive and highly specific biomarkers to update the definition of this disease.

Suboptimal studies had established preoperative chemoradiation as the preferred strategy in the management of localized oesophageal cancer (LEC) and gastro-oesophageal cancer. The recent CROSS trial has now demonstrated considerable benefit from preoperative chemoradiation over surgery alone in patients with LEC. But, are these results only reinforcing advocates of the preoperative chemoradiation strategy?

Treatment of locally advanced non-small-cell lung cancer (NSCLC) in the elderly is challenging, with many available treatment options from radiotherapy alone to sequential chemoradiation. The latest phase III trial comparing radiotherapy alone with concurrent chemoradiation reported a survival improvement for the combination; however, this does not define a new standard treatment.

The PALETTE randomized phase III trial has reported a statistically significant benefit for the use of pazopanib compared to placebo in terms of progression-free survival for the treatment of soft-tissue sarcoma. However, no benefit in terms of overall survival was observed, the reasons for which might lie in the study design.