Small studies get big headlines at ASCO 2017

Nearly 40,000 cancer specialists have converged in Chicago for the world’s largest cancer meeting.

The American Society of Clinical Oncology (ASCO) meeting — which began last Friday and runs through tomorrow — traditionally draws international media attention. As our deputy managing editor, Joy Victory, reported last week, it has become a perennial exercise in spotting trends as well as separating hope from hype.

How did journalists covering the conference do this year? While we can’t possibly keep up with all the coverage, we did take a close look at three studies that were spotlighted by ASCO and thus seemed likely to generate a lot of media attention.

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Fulfilling the “promise of precision medicine”

It’s hard to know who coined the term ‘precision medicine’ … doctors or marketers. In the high stakes world of cancer therapy ‘precision’ means a treatment based not on the tumor’s location in the body (which has been the traditional approach) but on its specific genetic make-up. (We reported last month on the first such precision drug to gain US approval.)

But it’s still an emerging technology with mostly preliminary results. So the question remains: how precise is precision medicine?

An example from this weekend’s conference is a drug called larotrectinib which received Breakthrough Therapy Designation from the FDA one year ago. Preliminary results presented at ASCO this weekend showed that 76 percent of 50 patients had tumor shrinkage across 17 different types of tumors. Of those with tumor shrinkage, nearly 80 percent did not have the original tumors rebound — or any new tumors grow — after a year of therapy.

This prompted principal investigator, David Hyman — an oncologist who heads the early drug development program at Sloan Kettering Cancer Center — to claim the drug “fulfills the promise of precision medicine … this is a real breakthrough.”

But these are unpublished, preliminary results with an experimental drug using a surrogate marker as an endpoint: tumor shrinkage. As rightly pointed out by Reuters:

“Researchers have yet to determine other key benchmarks of performance, including median overall survival, progression-free survival, or duration of response.”

While shrinking tumors is a good thing, it may not ultimately lead to a benefit that patients care about such as extended life or higher quality of life.

Dr. Matt Katz is a radiation oncologist based in Massachusetts. He finds the gene targeting approach exciting, but says there are some things to bear in mind:

“From a scientific standpoint larotrectinib looks very promising for continued research. But that doesn’t mean it warrants FDA approval without some evidence that the surrogate marker is linked to improved survival. We need better safety data and also some projections of financial costs.”

Forbes magazine, in this well-researched article by Matthew Herper, was right to bring up the following:

• it is unknown how long the tumors will continue to respond
• treatment cost is also unknown but most drugs of this type start at $100,00 per year
• the mutations targeted by larotrectinib (TRK mutations) are involved in only about 0.5 percent of cancers
• the genetic tests needed to identify these TRK mutations are highly specialized and not widely available

One thing we found quite encouraging is that, although the lead investigator did use the term “breakthrough,” most of the coverage we encountered was more tempered than sensational.

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“Groundbreaking” results … tumor shrinkage (again) in 7 out of 15 women

Another targeted or precision therapy — this time an ovarian cancer drug called ONX-0801 — generated a fair amount of coverage in England (where the research was done at the Institute of Cancer Research, or ICR, in London).

Both The Guardian and the BBC did well to point out the trial was small, the treatment experimental, and the surrogate marker of tumor shrinkage did not necessarily equate to extended life. They also explained how the drug works (mimics the ability of folic acid to latch on to cancer cells) as well as contextual statistics on ovarian cancer.

The Telegraph, on the other hand, opted to err on the side of hype with “groundbreaking … gives months of extra life without side-effects … biggest breakthrough in a decade.”

This “breakthrough” claim – along with mention that the drug “should add upward of six months of extra life without side effects” – are attributed to researchers in the Telegraph article.

Given the size of this study, the lack of long term follow-up, and the reliance on surrogate markers as an endpoint, these comments are speculative. Including them borders on hype and has the potential to mislead readers.

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And now for something a bit more pragmatic

A study addressing whether it is safe for women who have been treated for breast cancer to get pregnant — including women with estrogen-sensitive (so-called ER-positive) cancer — shows that it’s just not the high-tech or dramatic that makes it from the ASCO meeting to the front pages.

A Brussels study of 1,200 breast cancer survivors under the age of 50 showed that those who became pregnant did not have a higher risk of cancer recurrence and death — when followed for a decade — compared to women who did not become pregnant. This even held true for the women who’d had ER-positive tumors (some breast cancers are stimulated by estrogen and pregnancy raises estrogen).

I spoke with Dr. Deanna Attai, who frequently contributes to this blog and was at ASCO, who thought the coverage she saw by Reuters and the Philadelphia Inquirer & Daily News was thoughtful and carefully worded. I asked Dr. Attai if this preliminary study would change how she talked about pregnancy with her cancer survivors.

“Historically we have discouraged women from attempting pregnancy after breast cancer but now we have this 10-year follow-up that shows no adverse outcomes. Yes there are limitations to this study: it’s not possible to undertake a randomized trial of breast cancer after pregnancy, and the number of women followed was small. Also, we know that some patients with ER-positive cancer may experience late relapses well past 10 years.

But this is a first step. I can not tell every patient that pregnancy after breast cancer is safe in their situation. But this abstract provides some reassurance and also reinforces the importance of discussing childbearing and fertility issues prior to starting breast cancer treatment.”

Of note, there is an ongoing clinical trial looking for women who are considering getting pregnant after breast cancer treatment. It’s called the POSITIVE trial and there is more information HERE.

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Every year the ASCO meeting serves as a barometer for many things. A shortlist would include emerging technologies, politics, research funding, and the big money that big companies invest in their intense marketing and public relations campaigns.

The financial stakes are high. A report published last week by the independent QuintilesIMS Institute showed that global spending on cancer drugs (including supportive medications like those used to treat nausea) reached $113 billion last year. That’s a jump of $22 billion since 2012.

But the emotional stakes are even higher.

Cancer patients often face daunting physical, mental, and financial burdens. Many peruse the mainstream media eager for any new information that might offer new hope. That’s precisely why we follow this conference so closely. Scientific research — and cancer research is a superb example — by necessity, moves forward cautiously and self-critically. Those of us who write about this research serve our readers best when we do the same.

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Here is our associate editor Kathlyn Stone’s coverage of the remainder of the ASCO conference:

High drug costs (and stock values) take center stage at final day of ASCO