Trials and papersMelanoma

Shows why single stories cannot settle the question: a melanoma this immunogenic can wax and wane on its own, and the improvement did not last.

For patients with advanced melanoma, immunotherapy offers a realistic chance of long-term survival and probably cure, and the ten-year data show that patients who are alive and progression-free at three years rarely die of melanoma afterwards. Nivolumab plus ipilimumab gives the best long-term results but at a high price in serious side effects; nivolumab alone or nivolumab plus relatlimab are alternatives for patients at lower risk or with autoimmune concerns. The trial is also a caution about surrogate endpoints: the survival plateau took years to become visible.

The uninjected-lesion responses are the most important result any oncolytic virus trial has produced, because they are the first strong clinical evidence that the mechanism is systemic immunity rather than local lysis. The caution is the same as always: this is a single-arm cohort in a population with no standard option, and the randomised confirmatory trial has not read out.

For the first time a randomised trial suggests that a vaccine tailored to an individual's tumour can reduce relapse when combined with immunotherapy, which is a proof of concept for a field that had failed for decades. Nothing changes for patients yet: the trial was small, the confidence interval crossed one, and the phase 3 trial in melanoma (and parallel trials in lung and other cancers) must confirm it. If it does, personalised mRNA vaccines could become a routine adjunct to checkpoint inhibitors after surgery.

Patients with melanoma that has spread to palpable lymph nodes should now be offered immunotherapy before rather than only after surgery: two cycles of low-dose ipilimumab with nivolumab, then surgery, with the pathology result deciding whether any more treatment is needed. Most patients respond well and are spared a year of adjuvant therapy. Serious side effects are more common than with nivolumab alone, mostly endocrine, and the approach requires close coordination between oncologists, surgeons and pathologists.

This series is the standard reference for US cancer numbers and the source of most headlines about cancer in younger adults. The gap between falling mortality and rising incidence is the argument for both continued treatment advances and stronger prevention and screening.

Pancreatic cancer was thought to be immunologically inert because of its low mutation burden; this study showed that with the right vaccine platform its few neoantigens can still be targeted. It is the strongest human evidence so far that personalised cancer vaccines can generate durable, tumour-specific immunity, and it justifies the randomised trials now running in pancreatic cancer and melanoma. Benefit is not yet proven, because responders may simply have had more immunogenic tumours.

Rigvir is the field's clearest case of a product sold far ahead of its evidence: a national registration, international marketing to patients, and no randomised trial. This is the laboratory work that should have been done first. It is here because a field that produces striking single cases attracts exactly this, and readers deserve to know that an approval somewhere in the world is not the same as evidence.