Rare driver mutations: BRAF- and HER2-mutant NSCLC

BRAF driver mutations in NSCLC are rare at 2 %, but tumours with BRAFV600E mutations have histological features suggestive of aggressive biology. When treated with platinum-based chemotherapy, these patients showed less favourable outcomes.  The multi-cohort, non-randomised, phase II BRF113928 study investigated a targeted approach using the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib in patients with advanced BRAFV600E-mutated NSCLC.

ALK-positive NSCLC: updates on crizotinib and alectinib

PROFILE 1014 was the first study to define the role of the ALK inhibitor crizotinib in the first-line treatment of patients with ALK-positive lung cancer. It compared crizotinib 250 mg twice daily (n = 172) with pemetrexed plus cisplatin (n = 171) in patients with ALK-positive, locally advanced, recurrent or metastatic non-squamous NSCLC in the first-line setting.

Characteristics and outcomes for SCLC arising from transformation

A low but significant proportion of EGFR-mutant adenocarcinomas transforms to SCLC at the time of acquisition of resistance to EGFR TKI therapy. Moreover, cases of de novo SCLC harbouring EGFR mutations have been reported. As the clinical characteristics and clinical course of SCLC-transformed EGFR-mutant lung cancer are largely unknown, Marcoux et al. retrospectively reviewed the records of 16 patients with EGFR-mutant SCLC treated between 2006 and 2017.

Reaching unprecedented outcome dimensions in malignant mesothelioma

Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer with poor prognosis. While combination chemotherapy with platinum and pemetrexed with or without bevacizumab is a standard in first-line treatment, no approved second-line strategies have been established to date. Gemcitabine or vinorelbine are often used in this situation, but these only show limited activity.

Interview: “Survival is the result of multiple treatment lines”

FLAURA is a positive trial, as its results favour osimertinib over gefitinib and erlotinib. Now we have to consider this among the multiple options that are available for the first-line treatment of EGFR-mutant lung cancer. Besides osimertinib, there are the first-generation TKIs erlotinib and gefitinib and the se­cond-generation TKI afatinib, but maybe sometime soon also dacomitinib, for which data were presented at the last ASCO Meeting.

EGFR-mutant lung cancer: sequencing as a major topic in light of new data

The first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) erlotinib and gefitinib as well as the second-generation EGFR TKI afatinib are the recommended first-line options for patients with EGFR-mutant NSCLC. Regardless of the extent of initial response, however, more than 60 % of patients develop the T790M resistance mutation.

Randomised findings on CT-based follow-up after resection of early NSCLC

Regarding the optimal follow-up after surgery for early-stage NSCLC, the ESMO guidelines recommend patient surveillance every six months for 2-3 years with visits including history, physical examination and preferably contrast-enhanced spiral chest CT at 12 and 24 months. Thereafter, annual visits including history, physical examination and chest CT should be performed to detect second primary tumours (SPCs).

Immunostimulation as a promising approach in SCLC

There is a high unmet medical need regarding extensive-disease small-cell lung cancer (SCLC) that shows poor outcomes with median OS of 9 to 11 months. First-line chemotherapy usually evokes marked responses, but responders typically experience only limited periods of disease control.  Based on the hypothesis that activation of the immune system might prolong disease stability in these patients, thus ultimately affecting their survival, Thomas et al. assessed the activity of the toll-like receptor 9 (TLR9) agonist lefitolimod.

Immunotherapy: once more at the cutting edge of progress

Approximately one third of patients with non–small-cell lung cancer (NSCLC) presents with stage III, locally advanced disease. For those with good performance status and unresectable tumours, the standard of care is platinum-based doublet chemotherapy with concurrent radiotherapy. As no major advances have occurred in this setting over several years, there is a significant unmet need for novel therapeutic approaches to boost survival.

Preface – ESMO 2017

Remarkable data in the field of lung cancer with potentially practice-changing impact have been presented at this year’s ESMO Congress that took place in Madrid, Spain, from 8th to 12th September, 2017. Immunotherapeutic approaches again constituted a major topic, as clinical researchers are tirelessly exploring the multitude of conditions and limitations determining the optimal use of these drugs.

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