Recent story for news writers from Health News Review:

Six tips for writing accurately about cancer immunotherapy drugs

POSTED BY Joy Victory

Immunotherapy drugs that stimulate the immune system to fight cancer are a hot news topic, buoyed in part by high-profile apparent success stories like that of U.S. President Jimmy Carter who was diagnosed last year with metastatic melanoma.

As evidenced by some recent headlines, these stories tend to focus on the positive outcomes:

• TIME: A new cancer therapy leads to remissions
• The Guardian: Immunotherapy: the big new hope for cancer treatment
• Kansas City Star: For some KU cancer patients, altered immune cells give new hope
• ABCNEWS.com: The remarkable cancer treatment that helped Jimmy Carter combat brain tumor

The excitement around immunotherapy is understandable–for a small number of people, they work. These powerful patient stories often overshadow the reality that for most people, they aren't very effective and carry significant drawbacks.

Drawing upon several of our reviews on this topic, we've put together the following tips to help journalists balance out their coverage on these drugs:

1. Discuss the steep costs

We always advocate for costs to be included in news stories looking at health interventions. This is especially important for pricey checkpoint inhibitors like Keytruda, the drug Carter used. As we point out in our review of a Reuters story looking at trial results for Opdivo, another checkpoint inhibitor, a year's worth of treatment costs about $250,000. Even with insurance, the out-of-pocket costs for these drugs are sending some patients into bankruptcy.

The pricetag alone is a staggering detail that readers deserve to know. And so are the fascinating unintended consequences that impact all of us.

And what about when drugs are still experimental? The Washington Post handled this well in a recent story about a t-cell immunotherapy for kids, as we note in our review of their story, because they give a cost estimate based on similar drugs already available.

2. Know your endpoints

In cancer trials, many studies rely on what are known as "surrogate endpoints" to measure the success of a treatment, instead of primary endpoints like overall survival rates, which require a big, long trial to reach statistically significant findings.

It varies, but these surrogates usually include how long the treatment kept the cancer from spreading ("progression-free survival"), or how much it shrunk or reduced tumors ("objective response rate").

For journalists, what matters here is that you explain how positive results related to surrogate endpoints are no guarantee of a longer, healthier life compared to standard treatment (see this chart for a very easy-to-understand explanation).

"Surrogate markers such as PFS and ORR are valuable in drug development; however, their utility and need for longer follow up need to be acknowledged," said oncology researcher Mike Thompson, MD, PhD, of Aurora Healthcare in Milwaukee.

This means if you are writing about a surrogate endpoint like tumor shrinkage, be specific and use actual numbers. And, as we discuss in our review of a Boston Globe story about a modified herpes virus treatment for cancer: Remind readers that surrogates often don't tell the whole story.

The Globe story indicates that the treatment caused some tumors to shrink for at least six months, particularly in those whose cancer had not yet spread to internal organs. But the overall discussion of benefits is lacking some important details. What does "shrink" mean? And when it says that 16% "responded," what exactly does that mean? (Of course, 84% did not respond — a statistic that also was worthy of comment in our view.)

Finally, important outcomes, such as length of survival, are not presented nor compared with alternatives. One study reported that median survival was 23.3 months with the new drug vs. 18.9 months with the comparison treatment — a finding that would have been easy to include. The FDA also had cautioned in a news release that Imlygic, the drug under study, "has not been shown to improve overall survival."

3. Ask: Does this drug extend life? Improve quality of life?

Lack of evidence around survival benefits is far more widespread than just the drug written about in the Globe piece. As a Milwaukee Journal Sentinel/MedPage Today analysis found, of 54 new cancer drugs approved in the last decade, "the FDA allowed 74% of them on the market without proof that they extended life. Seldom was there proof of improved quality of life, either." When extended survival was shown, their analysis found it usually only amounted to a just a few extra weeks or even days.

In the above example from the Boston Globe, the FDA disclosed that the drug had not been shown to improve overall survival. But, often news releases from the FDA, drug industry and medical research centers don't clearly explain what the limitations were, as we saw in our news release review on the drug Tecentriq.

In this case, the FDA news release notes that a Tecentriq trial measured tumor shrinkage as the main outcome. Survival isn't addressed. Yet–and our hats off to them for doing so–the New York Times wrote about Tecentriq and wisely pointed out that it is unknown whether the treatment makes a difference in survival.

4. Don't assume these drugs are easier on the body

The oncologist goes deep with publisher Gary Schwitzer on many of these issues, from surrogate endpoints to the flailing promise of precision oncology. Take a listen here.

Immunotherapy drugs are often described as "lifesavers" and "game changers." A recent Pittsburgh Post-Gazette story described how the side effects may even "pale" in comparison to chemotherapy.

And for some people, that's true. But the reality is these drugs have severe side effects, and can produce disabling conditions, including severe colitis and widespread arthritis.

"These are treatments that have toxicities, and they may be different (and in some cases worse) than the toxicities from standard chemotherapy," said Deanna Attai, a breast surgeon and assistant clinical professor of surgery at the David Geffen School of Medicine.

Also important to know is that our understanding of immunotherapy's full impact is still unfolding, something hinted at in this Medpage Today story about the "novel" emergence of inflammatory arthritisamong immunotherapy patients at a cancer center affiliated with Johns Hopkins.

Some of this is because these drugs are relatively new and therefore carry unknown risks, and some of this is because, as this systematic review concluded, reporting of immune-related adverse events in research trials involving immunotherapy is suboptimal and "often incomplete."

5. Understand how these drugs fit (and don't fit) into "precision oncology"

Immunotherapy should not be confused with precision oncology, which is the notion that genetic sequencing can reveal mutations that help optimize treatment. Instead of focusing on the type of cancer (lung or breast or colon, for example), treatment is targeted based on the type of genetic mutation seen. In some cases, an immunotherapy drug might be used, but mostly it involves other types of cancer drugs.

What immunotherapy and precision oncology have in common is a lot of hype over relatively lackluster results, notes Dr. Vinay Prasad, a hematologist-oncologist and Assistant Professor of Medicine at the Oregon Health and Sciences University, who wrote about the "precision-oncology illusion" in Nature.

"Data from some 2,600 people enrolled in a sequencing programme at the MD Anderson Cancer Center in Houston, Texas, showed that just 6.4% were paired with a targeted drug for identified mutations. Similarly, the Molecular Analysis for Therapy Choice (NCI-MATCH) trial at the US National Cancer Institute has enrolled 795 people who have relapsed solid tumours and lymphoma, but as of May 2016 it had only been able to pair 2% of patients with a targeted therapy."

And, even in the rare cases where a drug is found to be a good match for the patient's biological markers, this doesn't guarantee blockbuster results. Prasad reports that only about 30% of these patients see any improvement.

"At best, we may expect short-lived responses in a tiny fraction of patients, with the inevitable toxicity of targeted therapies and inflated cost that this approach guarantees," he says in the Nature review.

6. Determine if your patient interview is with an 'exceptional responder'

And yet, even though they do not represent the typical scenario, it's this "tiny fraction" of patients who have exceptional results– from immunotherapy or precision oncology treatments–who often make their way into news stories, Prasad says.

"When you read the lay public coverage of cancer medicine today, you would walk away with the idea if only you could get your tumor sequenced, you could be almost assured of finding out something we already have that could give you a tremendous lease on life," he said in a podcast interview with us. "That's the narrative that's been put out over and over in anecdotal news stories about the one person who does really well."

Yet, more often than not, that one person is what oncologists like Prasad call a "super responder."

"In reality, many people profiled are unusual before they took the drug: They already lived far beyond expectations," Prasad said.

This is why it's important to interview a variety of patients, and not just the ones with incredible results. (That said, stories that only profile one patient can be done well, as we saw in our review of a Philadelphia Inquirer story about one man's ups and downs of using a type of immunotherapy for leukemia.)

To make sure that an exceptional patient isn't misleadingly portrayed as a typical patient, Prasad offered tips on how to sift them out. His advice included asking the following:

1. Before the super-responder patient got the "new" drug, had their course been average? Or were they already beyond average? Did they respond wonderfully to early therapy?
2. Did they already outlive life expectancy?
3. How many prior treatments had the super-responder gotten? How many treatments does the average person get? (Because people with naturally slow growing cancers live long enough to get many treatments.)
4. What was the best response to therapy (did the cancer shrink or just grow slower)?

Bottom line: There is understandable excitement surrounding these drugs that extend life for some patients who've run out of options. But as journalists, we have a responsibility to not let this enthusiasm run beyond what the evidence can support–what Prasad calls fostering false optimism.

"People who are suffering from cancer have one of the most challenging…experiences any of us can have," Prasad said in the podcast interview with us. "We do them a service if we can do better by covering cancer therapies for what they are, by being more accurate about the use of new drugs."

Wow- very valuable information. Hopefully she has found a good treatment now, and I agree its critical that they tell you whether or not it was the drug that likely caused her liver problems!

I've been on the Sandpiper trial for 18 months now. Initially I had mouth sores and diarrhea and rash throughout my body. My oncologist decreased taselisib to 2 mg 1 tablet instead of the 2. I continue to have mild diarrhea and am on loperamide to help control it. The target mass initially reduced in size but my last 2 ct scans show that it is stable or slightly bigger but not enough to be removed from the study.

Nnc-

Thank you so much for sharing your experiences with this clinical trial! We wish you success on the remainder of your trial!

The Mods

NNC - You had a great run on the sandpiper trial. Good luck on Exemestane. I appreciate so much that you share your experience with us.

Ask you doctor for the clinical trial results supporting the use of Affinitor, particularly the ones that have looked at overall survival as an endpoint. From what I have read, Affinitor doesn't help much with the endpoint I am really concerned about, Overall Survival, and the side effects are bad.

Praying for your complete healing.

>Z<

Great article Cure-ious. The answer, I believe, is going to be a cocktail of drugs. It's just a matter of which ones for whom and when at what doses.

>Z<

Tarheel, you may want to consider Cymbalta for AI-related joint pain. It worked wonders for me when I was on hormone therapy with no noticeable side effects.

I am on cycle 22 with Sandpiper phase III. Last blood test shows increase of marker CA-15-3 to 45. CT and bone scans scheduled in 3 weeks. Pain in spine is increasing. I believe my course is coming to end.

Not a flare up unfortunately. Am off the trial due to progression. Awaiting appointment for liver biopsy.😥.

This trial does not release information if it was a placebo or not but in the few weeks of the drug my glucose has dropped. Increase levels of blood sugar was a known SE.

On Tamoxifen as of June 13Th.