Dear Oncology Fellows: We Must All Stand Up For Patients

Career aspirations must come secondary to research that always and only advances patient interests

By Aaron Goodman, MD and Vinay Prasad MD MPH

We are two practicing hematologist-oncologists, who care for people with a wide range of solid (VP) and liquid cancers (AG & VP), and we are concerned about the state of our field.

As trainees, we dreamed of becoming attending oncologists who took care of sick patients in their times of greatest need, while conducting meaningful research that advanced patient care.  We suspect most of our colleagues shared similar ambitions.

We doubt many of us dreamed of becoming a “thought or key opinion leader” running clinical trials— designed and written by the pharmaceutical industry—that fail to advance care, while simultaneously harming patients in the control arm.  Nearly no one lay in bed at night dreaming to be first author on manuscripts published in The Lancet or New England Journal of Medicine written by industry financed medical writers.   Yet, somewhere during our early career, these nightmare scenarios became what many began to aspire for or, at least, quietly accept.

We can only imagine what a younger version of ourselves would say if we presented clinical trial results on the plenary session stage at a major conference to a standing ovation where half of enrolled patients with a life threatening malignancy received a substandard treatment we wouldn’t dare to prescribe to our own mothers.

Just this week the New England Journal of Medicine published results of the latest $20,000 a month cancer drug to great fan-fare.  The drug, rucaparib, increased radiographic progression free survival against a ‘physician’s choice’ of treatment, and Twitter erupted in celebrations for the sponsor, the conference #GU23 and the doctors who worked on the study.

We read the paper closely, and wondered if we were talking about the same drug.  Overall survival– how long cancer patients lived was entirely unchanged– the curves superimposable. Patients didn’t live a day longer!

Vinay Prasad MD MPH @VPrasadMDMPH

Here are the issues with #TRITON3 #rucaparib #GU23 Brief 🧵 Follow @Plenary_Session for more 1 Overall survival unchanged This is pathetic 👇 PS we don't need surrogates when OS is readily measurable & null nejm.org/doi/full/10.10…

The control arm was called “investigator’s choice” but that was a misnomer. Investigators had to choose from a limited menu of 3 drugs, of which patients had already received 1, and some had even received 2!  These drugs are known for not working well in this scenario—when you have already gotten one or the other.  Useful drugs that are routinely used in prostate cancer were prohibited.  

Finally, what is radiographic PFS?  It is a mathematical endpoint that looks at the size of tumors on scans, declaring progression at arbitrary thresholds, but does not capture how long people live or how well they live.  Why was that the primary endpoint?  Twenty years ago in prostate cancer it was routinely the case that overall survival was the primary endpoint. Twenty years later, and our evidence is weaker. Is this progress?

We both agonized:  what if this were our own father?  Would we have enrolled him on this study?  Or, having read the paper, how can we take these results and advise him?

“But son, do I live longer or better?”

“I don’t know, Dad, I don’t know.”

This is hardly an isolated incident– there are dozens of flawed drugs and trials in recent years– selinexor (BOSTON), olaparib (POLO and PROFOUND), Lu177-PSMA (VISION), ibrutinib (SHINE), and the list goes on and on.  

Every week on twitter there is a new “practicing changing” trial and all the drugs are “game changers.”  But in clinic, patients often die with added toxicity, nearing bankruptcy– all based on inadequate data, and impossible conversations.

“Well, we do know your radiographic PFS will be longer than a flawed control…”

It’s time to stop the madness.

We know no medical student, no resident, no fellow in oncology who aspires to work on trials that use (a) substandard controls (b) have substandard post protocol therapies © unproven surrogate endpoints (d) informative censoring (e) unfair drug doses and more— and yet this is what we are given.

We have even seen recent commentaries try to defend the status quo, or even criticize us for not using a more pleasant tone in our critiques. “Pharma-scolds,” some pejoritively call us. We prefer the term “patient advocates”  We are sorry you don’t like criticism, but patient lives are on the line– forgive us for not thinking more about your feelings.

We urge fellows to take a simple pledge, as they become oncologists:

1.  I pledge to only enroll my patient on a clinical trial, if I would feel comfortable enrolling my own father or mother on the control arm

2. I pledge to only publish research that I believe in/ which I believe is true

3. I pledge to write my own manuscripts (declining pharmaceutical writer support)

When you dreamt of being a doctor, is the current system what you had in mind? 

If not, it is time to fight back.  We are not powerless. We don’t have to rationalize the system. We can acknowledge the tremendous financial and medical injustice that is modern oncology.  We can speak up, and air our voices.  

We can remember our goal was to enter oncology to do good, not stay to do well.

Pushing for change isn’t always easy. We have both endured insults, and been advised to take it easy on a specific company, specific drug or specific trial. A cancer center director once told one of us  “crawl into the hole from which we came from.”

Yet, Plenary Session— a critical podcast one of us hosts— has reached all time highs, getting tens of thousands of downloads per episodes, with thousands of trainees and junior colleagues eagerly awaiting the next episode to drop.  

Perhaps that’s because we have hit a nerve and are on the right track.  

PS:  For folks interested in the methodological issues in drug development, such a analyses of trials like the one mentioned, subscribe to developdrugs.substack.com, coming soon— a new venture by Vinay Prasad, and listen to Plenary Session podcast.