'This is not experimental anymore': How immunotherapy is being used for some lung cancer and melanoma patients

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Last Monday headlines announced some encouraging cancer news — Lung cancer patients live longer with immune therapy.

Yet just 10 days earlier, different headlines reported that another experimental treatment didn't work — Incyte-Merck trial failure deals a blow to cancer immunotherapy.

A major success and a big failure in less than two weeks? It's the sound of science unfolding in real time.

For decades, scientists have been trying to manipulate the human immune system to attack cancer. It's called immune therapy (or immunotherapy) and if it works it will harness the body's own natural killing cells to eliminate tumours.

But how much of the immune therapy hype has translated into real change for Canadian cancer patients?

This week we asked some experts and they told us that, for some lung cancer and melanoma patients, immune therapy is already "game changing."

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"This is real. This is not experimental anymore," said Dr. Frances Shepherd, lung cancer oncologist at Princess Margaret Cancer Centre in Toronto. "This is a sea change for us in lung cancer."

It has been astounding this new class of drugs has been so successful.- Dr. Frances Shepherd

"It's very clear we're seeing long-term survival. It's really changed things dramatically," said Dr. David Hogg, a melanoma specialist at Princess Margaret Cancer Centre. He says for patients with advanced melanoma the survival five years ago — before the dawn of immunotherapy — was only about five per cent.

"The survival now is well over 50 per cent at five years so that's an increase in one order of magnitude so this is why we're sort of excited about it."

Immunotherapy is emerging — slowly — as a distinct form of cancer treatment. It joins surgery, radiation and chemotherapy, becoming a fourth pillar of oncology therapy.

When Canadian doctors talk to their patients about immunotherapy now, they're usually talking about one class of drugs, called "checkpoint inhibitors," which have been approved to treat a few cancer types at specific stages, including metastatic melanoma, lung cancer, lymphoma, and some forms of kidney, liver, bladder and head and neck cancers.

The checkpoint inhibitors are infused into the blood where they find the body's natural cancer-killing immune cells and keep them switched on so they can attack tumours.

"It has been astounding this new class of drugs has been so successful," said Shepherd. She said the drugs have in some cases doubled the response rate — the rate that the drugs are able to shrink tumours. They've also extended the time before cancer progresses and in some cases are allowing patients to live longer.

Sometimes they're used after chemotherapy has failed to stop the cancer from progressing. But for some patients with specific types of tumours — ones with markers that indicate they're especially susceptible to immunotherapy drugs — it could be the first treatment they're given.

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Patients avoid the common side-effects of chemotherapy, including nausea and hair loss.

"Chemotherapy knocks your immune system down and conversely immunotherapy activates it," said Hogg. "It's almost the direct opposite."

But it also means there's a risk of new adverse effects if the highly activated immune cells start attacking healthy tissue. It can lead to inflammation of the lungs, liver and most dangerously, the heart.

Cost of these drugs is 'unconscionable'

And while the clinicians are excited about progress after years of disappointment, even daring to talk about "cures" where there used to be no hope, they are wary of raising patient expectations too high.

"There is a lot of hype in the media and patients expect a lot," said Shepherd. "It's always a disappointment when they don't respond."

"But when patients come back over a year later and they're healthy and not dragged down by the side effects of ongoing chemo it's wonderful to see," she said. "We're turning lung cancer into a chronic disease."

That means patients could be on the immune therapy drugs for years — coming back to the hospital for infusions every few weeks.

And that raises the controversial issue of cost. The drugs can cost more than $10,000 per month, over $100,000 per year. It means provinces are forced to decide which drugs to pay for, based on which patients are most likely to benefit.

"These drugs are extremely expensive and in fact I think the cost of these drugs is unconscionable," said Hogg. "They're set based on what the market will bear."

"In terms of cancer and in terms of societal resources, I'm not sure that's justifiable."

The main immunotherapy drugs used in Canada now are ipilimumab (Yervoy), pembrolizumab (Keytruda), nivolumab (Opdivo), durvalumab (Imfinzi) and atezolizumab (Tecentriq), but there are other checkpoint inhibitors poised to come into wider use soon.

The term immunotherapy includes other approaches to stimulate the immune system currently in development, including the much publicized CAR-T therapy where a patient's immune cells are removed and activated in a lab and then re-infused into the patient. Researchers are also using viruses to invade cancer tumours.

"There's many parts to the immune system. It's extraordinarily complex. We know a lot more about it now than we did a decade or two ago, but I think our understanding is still relatively primitive," said Hogg.

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