Memorial Sloan Kettering Cancer Center

Before 2011 median survival in metastatic melanoma was under a year; this trial shows that roughly half of patients treated with combination checkpoint blockade are now long-term survivors, effectively cured. It anchors first-line treatment of advanced melanoma and sets the benchmark for every new regimen, including nivolumab-relatlimab. The combination's toxicity means nivolumab alone or newer doublets remain reasonable for some patients.

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.

Young adults with a grade 2 IDH-mutant glioma who have had surgery can now take a daily tablet that slows or reverses tumour growth and defers radiotherapy and chemotherapy, both of which carry long-term cognitive costs, by years. It confirms that the IDH mutation is a driver that can be targeted, not just a marker. Whether it improves survival or cognition over the long term, and whether it helps in higher-grade or previously treated tumours, is unknown.

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.

Cercek's dostarlimab study is the clearest demonstration that immunotherapy can replace surgery in a solid tumour: patients with dMMR rectal cancer can keep their rectum and avoid the permanent effects of pelvic radiotherapy and surgery. Non-operative management after PD-1 blockade is now in guidelines for this group, and MMR testing before treatment of rectal cancer is essential. The approach applies only to the 5-10% of rectal cancers that are dMMR.

Patients with rectal cancer whose tumour is mismatch-repair deficient (about 5-10% of rectal cancers) can now be offered immunotherapy alone with the realistic expectation of avoiding surgery, radiotherapy and a permanent stoma. This requires mismatch repair testing on the diagnostic biopsy, close endoscopic and MRI surveillance, and treatment in an experienced centre. It does not apply to the 90% of rectal cancers that are mismatch-repair proficient.

Patients with newly diagnosed advanced stomach or oesophageal adenocarcinoma whose tumour is HER2-negative and PD-L1 positive (CPS 5 or more, or at least 1 in some regions) should receive chemotherapy with nivolumab (or pembrolizumab, from KEYNOTE-859), which adds about three months of median survival and doubles the chance of being alive at three years. The benefit in PD-L1-negative tumours is doubtful, and these patients may be better served by chemotherapy alone or by trials.

Routinely asking patients how they feel between visits, and acting on the answers, is a treatment in itself. It catches problems early, keeps people on effective therapy longer and appears to extend life. Cancer centres now build symptom monitoring into electronic records, though implementation is uneven.