Preface – ASCO 2015

Dear Colleagues,

As for many other oncological diseases, the management of lung cancer has undergone major changes in the last few years with the rise of targeted therapies, and more lately, of immunotherapy. These advances are reflected in the results of experimental research and clinical trials that were presented at the Annual Meeting of the American Society of Clinical Oncology that took place in Chicago, from 29th May to 2nd June, 2015.

Patient improvement is of paramount importance, especially with respect to lung cancer, and particularly in the second-line setting, considering the poor prognosis that is still linked to this disease. The majority of patients are diagnosed at advanced stages. Not too long ago, there was little left to offer them except for chemotherapy of mediocre activity in terms of prolongation of life and sometimes even symptom relief. Nowadays, the physician faces a vast range of available therapies to choose from. Many of these agents have proven to be highly effective, giving hope to both patients and physicians even in settings in which the decline of the patient’s condition used to be inevitable. Time and again, cases are being reported at meetings and congresses that demonstrate disease control in the metastatic situation. The abbreviation “NED”, which stands for “no evidence of disease”, is slowly but surely making its way into the files of oncology patients.

However, quite a few of the new drugs require genetic testing prior to use, as only certain subsets of patients can be expected to benefit. Even therapies that are not restricted to particular groups frequently do not work alike in all patients, as they might greatly improve the course of the disease in one patient but not in another, without any recognizable features to explain these differences. Moreover, specific toxicities need to be kept in mind, thus massively increasing the complexity of side-effect management. Thus, in modern practice, a considerable proportion of the time used on patient care is dedicated to this aspect of treatment.

The chapters presented in this publication summarise the recent findings in the fields of metastatic non–small-cell lung cancer (NSCLC), immunotherapy, SCLC, biomarkers, and local and regional lung cancer. Naturally, targeted agents are the ‘stars’ of the coverage, but other long-standing strategies, such as chemotherapy and radiotherapy, enter the stage as well.

In metastatic NSCLC, EGFR tyrosine kinase inhibition has become a mainstay of treatment in patients with activating EGFR mutations, although resistance frequently develops. This need is addressed by the development of mutant- selective EGFR inhibitors, which show promising activities. Other genetic anomalies that constitute therapeutic targets include RET and ALK rearrangements as well as BRAF mutations, with the prevailing armamentarium being constantly expanded. However, a second- generation platinum compound that offers reduced toxicity has also been found to provide advantages when tested in patients with squamous-cell carcinoma.

Research in immunotherapy is currently proceeding beyond the first PD-1 antibody nivolumab, which has shown highly favourable effects. New agents are already being tested with success. Great hopes in the treatment of SCLC are also being pinned on immunotherapy, as this disease responds poorly to standard approaches. No final answers have yet been found to the question of biomarker expression in the context of immunotherapy. So far, various analyses have generally revealed conflicting results on the predictive power of biomarkers. More research is called for in this field.

For local and regional lung cancer, in terms of overall survival, chemoradiotherapy followed by pemetrexed consolidation was not superior to commonly used chemoradiation regimens followed by consolidation regimens of choice, although at the same time it showed higher tolerability. BRCA1 expression is gaining importance as a prognostic and potentially predictive factor in the adjuvant setting. Customisation of chemotherapy according to BRCA1 levels has been demonstrated to be feasible in nodepositive resected NSCLC.

All of these findings will hopefully contribute to further improvements to our daily management of lung cancer patients. Although the defeat of cancer remains a long-term goal, the progress that has been made is truly encouraging, making us look forward to further data that will be presented at the upcoming congresses.

We are going through an exciting time in lung cancer.

Author: Barbara Melosky, MD, FRCPC, University of British Columbia and British Columbia Cancer Agency, Vancouver, Canada