Highly cited articles Original research De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017 G Curigliano, H J Burstein, E P Winer, et al. 3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3) F. Cardoso, A. Costa, E. Senkus, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab A. M. Menzies, D. B. Johnson, S. Ramanujam, et al. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials D. Arnold, B. Lueza, J.-Y. Douillard, et al. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial L. Paz-Ares, E.-H. Tan, K. O

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Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy

Neoadjuvant chemotherapy (NAC) is a commonly utilized strategy for the treatment of early-stage triple-negative breast cancer (TNBC). A major advantage of this strategy is the ability to observe the tumor response to chemotherapy. Pathologic complete response (pCR) is a well-established end point of NAC clinical trials, and serves as a useful prognostic marker as pCR is independently associated with improved survival outcomes compared with patients without pCR [2].

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Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge

Patients with KRAS/NRAS (RAS) wild-type metastatic colorectal cancer (mCRC) have improved survival when treated with anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies. However, these agents do not benefit patients with oncogenic RAS mutations [1–4]. Though less common, alterations in BRAF/HER2 and MAP2K1 (MEK) are additional biomarkers of primary resistance to anti-EGFR [5–7].

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REVERCE: a randomized phase II study of regorafenib followed by cetuximab versus the reverse sequence for previously treated metastatic colorectal cancer patients

The treatment of metastatic colorectal cancer (mCRC) has evolved considerably over the past two decades [1, 2]. Two randomized trials in the first-line setting compared chemotherapy with bevacizumab versus anti-epidermal growth factor (EGFR) monoclonal antibodies for patients with wild-type (WT) KRAS exon 2 mCRC [3, 4].

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OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer

Human papillomavirus (HPV)+ oropharyngeal squamous cell carcinoma (OPSCC) is a distinct entity with RTOG 0129 reporting long-term overall survival (OS) of 71% for stage III/IV HPV+ disease compared with 30% for HPV-negative tumors after concurrent chemoradiotherapy (CRT) [1]. Since full-dose CRT imparts considerable toxicity, [2, 3] de-escalation for favorable HPV+ OPSCC represents a rational strategy.

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Paclitaxel with or without trametinib or pazopanib in advanced wild-type BRAF melanoma (PACMEL): a multicentre, open-label, randomised, controlled phase II trial

Although substantial progress has been achieved in the management of unresectable and metastatic melanoma, it remains a fatal disease. Impressive anticancer activity has been shown by kinase inhibitors, which target aberrant signalling in the 50% of melanomas with BRAF mutations, and antibodies that bind to the immune checkpoints cytotoxic T-lymphocyte antigen 4 (CTLA-4) or programmed death 1 (PD1) [1–3].

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Larotrectinib in adult patients with solid tumours: a multi-centre, open-label, phase I dose-escalation study

Oncogenic NTRK gene fusions encoding constitutively activated TRK tyrosine kinases occur across a wide range of tumours. Larotrectinib is a first-in-class potent and highly selective inhibitor of TRK kinases. In this first-in-human, phase I dose-escalation study, we showed that larotrectinib was well tolerated and provided consistent and durable antitumour activity in adults with TRK fusion cancer.