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Legislators in the USA have been discussing reforms to reduce the high cost of brand-name drugs, which are much higher in the USA than in other industrialized countries. One solution is to actively negotiate prices based on drugs’ clinical benefits. We discuss two important complexities from such an approach: drugs that have been approved for multiple indications and as part of a combination regimen.
Daratumumab is an anti-CD38 monoclonal antibody that has transformed the landscape of treatment both for transplant-eligible and -ineligible patients with newly diagnosed multiple myeloma. Addressing important ongoing questions, such as when to de-escalate therapy, will be an important step forward in delivering patient-centred care for those with newly diagnosed multiple myeloma.
Efforts are being made to incorporate immune-checkpoint inhibitors into therapy for early stage non-small-cell lung cancer. The IMpower010 trial of adjuvant atezolizumab has recently become the first study to demonstrate that this strategy can improve disease-free survival in a subset of patients. This trial opens a new area of research in the quest for the optimal perioperative strategy to increase overall survival.
Fluorescence-guided surgery (FGS) using tumour-targeted imaging agents has emerged over the past decade as a method of intraoperative cancer detection; however, the clinical implementation of tumour-targeted FGS remains in the early stages. The authors of this Review discuss how target selection, imaging agents and detection systems could enable real-time intraoperative visualization to benefit patients with cancer.
The MYC proto-oncogenes are among the most commonly activated proteins in human cancer, yet the clinical efficacy of MYC-targeted agents remains to be demonstrated. The authors of this Review describe how activation of the MYC pathway affects cancer cells as well as the tumour microenvironment and propose strategies for the therapeutic targeting of MYC-driven cancers.
Immune-checkpoint inhibitors have dramatically improved the outcomes in patients with advanced-stage cancers, although the majority of patients will not respond to these agents. Here, the authors describe the potential of targeting emerging immunomodulatory pathways, with a focus on alternative immune checkpoints and tumour metabolism as approaches that might enable further improvements in the outcomes of patients with cancer, either as monotherapies or in combination with existing agents.
EGFR exon 19 deletions and exon 21 mutations, and HER2 amplification and/or overexpression, are predictive of response to matched molecularly targeted therapies that have greatly improved patient outcomes. However, insertion mutations in exon 20 of either EGFR or HER2 generally do not confer sensitivity to these therapies. In this Review, the authors discuss the prevalence of EGFR and HER2 exon 20 insertions across cancers, their biology and detection, and associated responses to current molecularly targeted therapies and immunotherapies. In addition, they focus on new therapeutic strategies that are being developed to target tumours driven by these non-classic EGFR and HER2 alterations.
