Doubling-up on cancer immunotherapy shows promise, but side effects still a challenge

A combination of two immunotherapy drugs outperformed a single drug treatment in patients with a type of advanced lung cancer, according to ‘exciting’ early results presented at the world’s largest cancer conference. 

The findings led experts to say that doubling-up on immunotherapy is the ‘next step’ in the growing promise these treatments hold. 

But the trade-off in seeing more tumours respond to combined drugs was more severe side effects, said researchers presenting findings at the 2016 ASCO conference in Chicago.

Dr Scott Antonia, from the Moffitt Cancer Center in the US, is studying small cell lung cancer, which is difficult treat if it returns after chemotherapy.

“It has been a stubborn disease, and not for the lack of trying,” he told a packed room of scientists. 

“We’re still giving the same chemotherapy as 30 years ago. People respond, but many will relapse, and the response rates then plummet with next round of therapy,” he said.

“It’s quite hopeful that we’ll be able to change this with immunotherapy.”

Antonia’s combination approach centres on a group of immunotherapy treatments called checkpoint inhibitors, some of which release the ‘brakes’ on cancer-killing immune cells. Whether this works can depend on the amount of immune cells that are able to burrow into tumours. 

Other checkpoint drugs can boost the number of these cells present in a tumour by targeting a molecule called CTLA4. 

Tumours carrying lots of immune cells, such as some melanomas, have been shown to respond well when the immune brakes are released by targeting a molecule called PD-L1. Others, such as pancreatic cancers, which don’t carry many immune cells, don’t respond well at all. 

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Researchers call these different tumours ‘hot’ and ‘cold’ respectively, and Antonia described how small cell lung cancers fall into the latter category – indicating that combing the two types of immunotherapy may tip the balance.

In their study, also published today in the Lancet Oncology, the team split 216 patients with advanced small cell lung cancer that had already received chemotherapy into three groups. One group received the PD-L1-targeting drug nivolumab (Opdivo) alone, while the other two received a combination of nivolumab and the CTLA4-targeting ipilimumab (Yervoy) in different doses. 

In both cases, the combination treatment outperformed the single therapy. In one group, the combined treatment doubled the number of people who saw their tumour stop growing, compared to nivolumab alone. 

Professor Peter Johnson, Cancer Research UK’s chief clinician, called the results ‘exciting’, saying that treating these tumours is hard. 

“Small cell lung cancer that has come back after chemotherapy is extremely hard to treat,” he said. “So the finding that half of the patients who received two immunotherapy antibodies together had lived more than a year is exciting.”  

But these improved responses also came with more severe side effects.

“The side effects were greater with the combination,” said Johnson. “But this work means we can do larger trials with more patients to work out how much the combination might improve survival.”

In another type of lung cancer, called non-small cell lung cancer, this same combination of drugs also showed promise. In this case, the drugs were tested as the first treatments that patients received, so-called ‘first-line’ therapy. 

Dr Matthew Hellman, from the Memorial Sloan Kettering Cancer Center in New York, presented findings from a study of 129 patients with advanced non-small cell lung cancer. 

They found that combing the immunotherapy drugs almost doubled the number of patients who saw their tumours stop growing, compared to nivolumab alone. 

In some cases, such as a 54 year old man whose case was presented by Hellman, there were striking responses to these drugs. 

But Dr David Spigel, from the Sarah Cannon Research Institute, urged caution that it may be too soon to be sure of any survival benefit due to the small numbers of patients in the study.

And Cancer Research UK’s Professor Peter Johnson added that an important next step will be to work out why some patients’ tumours respond, and others don’t.

“This trial shows that, for some patients with lung cancer, using immunotherapy may be as good as chemotherapy, or even better,” he said. 

“Our challenge is to work out which patients will see this type of benefit, how to maximise the effectiveness and minimise the side effects.”  

Commenting more broadly on the move to combining immunotherapy drugs, Memorial Sloan Kettering’s Dr Jedd Wolchock said the approach was the ‘next step’ for several cancers.

However, Wolchock also added that the combination approach “is going to take some tinkering before we know what will work for each patient”.

But it’s not just immunotherapy drugs that can be combined.

Results were also presented showing that a mix of two different types of re-engineered immune cells may improve patient survival in a range of different blood cancers.

The treatment involves taking immune cells from a patient and engineering them so that they target cancer cells. These re-engineered cells are called CAR T cells.

Dr Cameron Turtle, from the Fred Hutchinson Cancer Research Center in the US, presented data showing that when a mix of ‘killer’ CAR T cells and ‘helper’ CAR T cells where given to patients with acute lymphoblastic leukaemia (ALL), over 90 per cent saw their disease disappear. 

The same approach resulted in cancer disappearing in almost half of patients with Non Hodgkin lymphoma and chronic lymphocytic leukaemia.

“With ALL we have hit a home run,” said Dr David Porter from the University of Pennsylvania. “I fully expect that in 5 years’ time CAR T cell therapy will be standard practice for this cancer. But for other blood cancer types, such as CLL, we have made progress, but still have some way to go,” he added.

“But waiting out in the stands are the other cancer types, such as ovarian or bowel cancer, where we have only just begun to consider how to target them with CAR T cells.” 

• Image credit: Wikimedia commons (public domain)