Can a short burst of radiotherapy help immunotherapy work better?

A small clinical trial has produced encouraging results from combining the immunotherapy drug pembrolizumab (Keytruda) with an unusual form of short-course radiotherapy for people with recurrent, unresectable or metastatic head and neck squamous cell carcinoma.

The approach is called Quad-Shot radiotherapy.

Rather than delivering radiotherapy every weekday for several weeks, as many head and neck cancer patients will be familiar with, Quad-Shot delivers four low-dose treatments over just two consecutive days. The treatments are given twice a day.

Researchers wanted to find out whether these short courses of radiation could work alongside pembrolizumab and potentially help the immune system attack the cancer more effectively.

Why combine radiotherapy and immunotherapy?

Pembrolizumab works by removing one of the “brakes” that cancer can place on the immune system, allowing immune cells to recognise and attack cancer cells.

Radiotherapy, meanwhile, does more than simply kill cancer cells in the area being treated. When cancer cells are damaged by radiation, they can release tumour material and signals that may make the cancer more visible to the immune system.

This has led researchers to investigate whether radiotherapy might effectively help prime the tumour for immunotherapy.

What happened in the trial?

The study involved people with advanced head and neck cancer who were receiving pembrolizumab and had a tumour in the head or neck that could safely receive Quad-Shot radiotherapy.

Of the 15 patients who could be assessed for tumour response, 47% responded to treatment.

Among all 20 patients who received treatment, the median progression-free survival was 9.2 months. This means half of the patients went at least this long before their cancer progressed.

Median overall survival was 14.9 months.

These results were encouraging enough for the researchers to conclude that the combination deserves further investigation.

What about side effects?

This is an important question for people with head and neck cancer, particularly those who have already undergone radiotherapy.

Many participants in this study had already received significant cancer treatment: 14 of the 15 patients assessed for response had previously received systemic treatment, and 11 had previously undergone radiotherapy.

Serious side effects did occur. Among the 20 treated patients, six experienced Grade 3 adverse events and two experienced Grade 4 events.

However, when patients themselves reported their symptoms and side effects, these did not substantially worsen over the course of the study.

The researchers concluded that combining pembrolizumab with Quad-Shot radiotherapy was feasible.

Why is this research interesting?

There is an important difference between this approach and simply giving more conventional radiotherapy.

Quad-Shot is deliberately short and relatively low-dose. A complete course consists of four treatments delivered over two days, and courses can be repeated between cycles of pembrolizumab.

For people with recurrent or metastatic disease—some of whom have already received extensive radiation to the head and neck—finding ways to use radiotherapy strategically rather than embarking on another long course of treatment could be valuable.

There is also a bigger scientific question being explored:

Can radiation help turn a tumour into a better target for immunotherapy?

If it can, the two treatments may potentially achieve more together than either treatment achieves alone.

But there is an important caution

This was a small Phase 2 trial without a randomised comparison group.

Only 15 patients could be evaluated for the study's main measure of tumour response.

That means we cannot conclude from this research that adding Quad-Shot radiotherapy to pembrolizumab is better than pembrolizumab alone.

The researchers are clear about this. Their results provide preliminary evidence of possible benefit, but the combination now needs to be tested in larger randomised clinical trials.

What does this mean for our community?

For people living with recurrent, unresectable or metastatic head and neck cancer, research into better ways of using treatments we already have is just as important as research into completely new drugs.

This study suggests that a very short course of carefully targeted radiotherapy may potentially enhance the effects of immunotherapy.

That possibility is particularly interesting for head and neck cancer, where many people with recurrent disease have already undergone radiotherapy and treatment options can become increasingly limited.

As with much of the research we have been sharing recently, this is promising rather than proven.

But it is another example of researchers looking beyond simply finding the next cancer drug and asking a more sophisticated question: how can we make our existing treatments work better together?

LInk https://jamanetwork.com/journals/jamaotolaryngology/article-abstract/2850118

The takeaway: Combining pembrolizumab with short-course Quad-Shot radiotherapy produced a 47% response rate in a small study of people with advanced head and neck cancer. The results are encouraging, but larger randomised trials are needed before we know whether adding Quad-Shot radiotherapy really improves outcomes compared with immunotherapy alone.