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For cancer therapies to succeed, induction of an anticancer immune response is required. Immuno-oncology approaches are shaping the treatment landscape for patients with advanced-stage melanoma and other solid tumours. These new approaches may enhance immune system activity to improve outcomes, including the potential to achieve long-term survival benefits in many patients.

New treatment options for patients with resected stage III melanoma have been established with the publication of the results of four pivotal randomized clinical trials, resulting in three drug approvals, with a forth expected, all within only 4 years. Herein, we put these advances into context.

Melanoma has emerged as the paradigm tumor for drug development through mutation-targeted therapies (inhibitors targeting BRAF, MEK, and c-KIT) and immunotherapy. Exploring the combinations of both approaches is a challenge that will require scientific rationale and the cooperation of the pharmaceutical industry. But, with these challenges comes another opportunity to change the paradigms in drug development.

The final analysis of the MSLT-1 trial confirms that sentinel lymph node biopsy (SNLB) does not improve survival in patients with melanoma >1 mm thickness. Subgroup analyses remain inconclusive. SNLB provides prognostic information for adjuvant therapy decisions, as recent data indicate that adjuvant therapies are effective in patients with positive sentinel nodes with an ulcerated primary.

In this Viewpoint, four of our Advisory Board members discuss the key challenges in clinical cancer research that need to be overcome to achieve tangible progress in the next decade. The issues and challenges include clinical development and testing of multiple agents in combination, design of clinical trials, tumour heterogeneity, drug development and trial design, and funding for cancer research. What have we learnt over the past 10 years and how should we progress in the next decade?

Immune-checkpoint inhibitors and BRAF-targeted therapy have revolutionized the treatment of advanced-stage, unresectable melanoma and have been successfully transitioned into the resectable disease setting as (neo)adjuvant treatments. The expanding range of treatment options available for resectable high-risk melanoma raises questions over selection of the optimal therapeutic strategy and agents for each individual. Furthermore, the use of perioperative therapy has potentially important implications for the management of patients who have disease recurrence. In this Viewpoint, we asked four expert investigators who have been involved in the key studies of perioperative systemic therapies for their perspectives on the optimal management of patients with high-risk melanoma.

Isolated limb perfusion (ILP) combined with melphalan and TNF-α produces striking response rates for the treatment of bulky melanoma metastases, soft tissue sarcomas and various other tumors. TNF-α-based ILP is a well-established treatment that helps to avoid amputations, and this represents an important approach that is now widely practiced in Europe.

Immune checkpoint inhibition is a novel approach to cancer treatment with enormous potential to improve the outcomes of patients with a range of malignancies. However, owing to this novel approach, a range of adverse events have emerged with different aetiologies to those of more conventional cancer treatments. In this Review, the authors describe the occurrence, and optimal management of adverse events resulting from use of immune checkpoint inhibitors.