Three in four patients with head and neck cancers that surgery cannot remove responded to a red-light treatment, with disease control reaching 95 per cent. Median overall survival was 26.9 months in a multicentre Japanese study of 40 patients.

Photoimmunotherapy uses red light to destroy tumour cells. The treatment received insurance coverage in Japan in 2021 for unresectable locally advanced or recurrent head and neck cancer.

Rakuten Medical chief executive Minami Maeda hopes it will become a fifth pillar of cancer treatment, saying it asks surgeons to 'put down their knives, and pick up this lightsaber'. He wants to treat all solid tumours, not only head and neck cancers.

Head and neck cancer accounts for more than 900,000 new cases a year worldwide. Many are unresectable at diagnosis or after recurrence, when the prognosis is poor.

How Red Light Targets Tumours

The drug Akalux, generically called cetuximab sarotalocan sodium, binds to the epidermal growth factor receptor on cancer cells and tags them with a light-activated dye. Red light is then applied to destroy the tagged cells.

The dye, called IR700, absorbs 690 nm red light. The conjugate then changes shape and stresses the cell membrane, letting fluid rush in until the cell ruptures.

Patients receive an intravenous infusion, followed 20 to 28 hours later by laser illumination under general anaesthesia. Up to four cycles can be given if needed, at least 28 days apart.

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What the Japanese Studies Found

The multicentre, retrospective study covered patients treated from January 2021 to August 2024. The objective response rate was 75 per cent, with median time to treatment failure of 6.0 months and progression-free survival of 6.2 months.

An earlier US phase I/IIa trial reported an unconfirmed response rate of 43.3 per cent and median overall survival of 9.3 months. Response was measured differently in the two studies.

The Japanese study's authors suggested that earlier treatment of local recurrence and subsequent therapies may help explain the longer median survival. PD-1 inhibitors were frequently used after photoimmunotherapy, although the retrospective study cannot establish whether the treatment sequence improved survival.

A separate single-centre study of 19 patients at Aichi Cancer Center Hospital found complete responses only in local lesions. Seven of 14 patients with local lesions achieved one, while regional neck lesions did not, even with repeat cycles.

Smaller, thinner tumours were more likely to achieve a complete response. Thinner lesions were also more likely to achieve a complete response after one cycle, while intermediate-thickness tumours sometimes required multiple cycles at shorter intervals.

Side Effects and Safety Risks

Side effects were common in the 40-patient study. Pain affected 92.5 per cent of patients and mucositis, an inflammation of the mucous membranes, 80 per cent. Haemorrhages occurred in 77.5 per cent, none at grade III or above.

Laryngeal oedema, or swelling of the voice box, affected 42.5 per cent, with grade IV in four patients. Overall, 17.5 per cent had a grade III or higher adverse event.

Laryngeal oedema can block the airway. Two patients needed emergency tracheotomy, after which preventive airway management was introduced for all patients except those with a permanent tracheostoma or nasopharyngeal cancer.

Two patients developed sepsis, at grades IV and V. The fatal case involved a patient whose mucositis was initially mild.

The study authors recommended close monitoring for one to two months, until mucositis resolves, because patients' conditions can deteriorate rapidly after discharge. Average hospital stay after treatment is about two weeks.

Limits of the Evidence

The 40-patient study did not formally assess quality of life because of its retrospective design. Prospective studies with objective quality-of-life measures are needed.

A phase III trial, NCT06699212, is testing pembrolizumab with the therapy as first-line treatment for recurrent head and neck squamous cell carcinoma. Rakuten Medical is running US phase III trials, targeting an FDA submission in 2028.

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