What Have We Got to Lose?


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The ASCO Post is pleased to reproduce installments of the “Art of Oncology” as published previously in the Journal of Clinical Oncology (JCO). For information on how you can submit your own essay for consideration in JCO’s Art of Oncology, visit http://jco.ascopubs.org/site/ifc/determine-my-article-type.xhtml#art-of-oncology

Tuesday morning was the regular time for the departmental meeting—an opportunity to discuss cases, troubleshoot, debrief, and expedite the necessary allied health referrals. As usual, patient cases were being discussed in alphabetical order of the attending oncologist. We were already three quarters of an hour in, and we still had not got to my solitary inpatient.

I looked out through the window distractedly. The sandstone spires of the old medical school stood proud and defiant in the middle distance but were all but dwarfed by the neighboring glass and steel research institutes. The shiny new buildings were sleek and impressive, grand temples dedicated to medical progress and promise. The big old jacaranda tree in the quadrangle was in flower, heralding the start of university exams. Christmas was just weeks away.

My phone blipped. A text. “Hi, can you see one of my patients regarding anti–PD-1 [programmed cell death protein 1]? Not melanoma though. They will self-fund. Also, can you cover me? Off to Denver for a meeting for a few days.” The message ended with a grimacing emoji. I looked up. Dave sat on the other side of the meeting room table, his eyebrows raised expectantly. “Okay,” I replied. “You owe me a snow globe.”

Meet Pete

Pete was 37 years old when metastatic cancer was diagnosed. A commercial airline pilot, he had a pretty young wife, Amy, and two children, Jack and Lucy. Since his diagnosis, he had undergone several rounds of treatment with various combinations of chemotherapy, monoclonal antibodies, and experimental therapies, and now, Pete was dying.

Midafternoon, I stuck my head through the open door of Pete’s room. “Knock, knock” I said.

“Come in,” replied a woman’s voice. It was Amy.

“Hello,” I introduced myself. “Your oncologist has asked me to come and see you.”

Amy had been sitting by Pete’s bedside, tapping away at a laptop, but as I entered the room, she put it aside and stood up. “Hi—we are glad you came. We have been waiting to speak with you.”

Pete was lying semirecumbent in bed, swollen waxy limbs protruding from underneath a tangle of bedsheets and light cotton blankets. He seemed to be asleep, but as I began talking, one eye opened. On the bedside locker sat a framed picture of a fit-looking man, a young woman, and two kids aged maybe 8 and 6. The woman was clearly Amy. The guy in the photograph looked like Buzz Lightyear. I presumed that Buzz was in fact Pete, despite the lack of resemblance.

Pete’s room was on the southern side of the building, with views over the international airport and the Pacific Ocean. In the distance, 747s and A380s organized themselves for takeoff, a steady procession of bright red tails and flying kangaroos.

“You have a nice view here. I understand that you are a pilot.”

Pete closed his eye again. “I used to be a pilot. They don’t let people with advanced cancer fly planes.”

Awkward silence and a deep breath. “Your oncologist has asked me to see you to talk about immunotherapy with anti–PD-1.” I had already reviewed his history and his scans.

“Yes,” interrupted Amy, “we have been reading all about it,” before reaching into her oversized handbag to produce a plastic folder containing the results of her research. Amy began flicking through the plastic sleeves of the folder to find what she was looking for. Flick. Flick. Flick. The headlines were recognizable upside down. Flick. Flick. Flick. “New hope for melanoma sufferers.” Flick. Flick. Flick. “FDA [U.S. Food and Drug Administration] approves cancer breakthrough.” Flick. Flick. Eventually, she stopped at a printout from the Internet, the results of one of the early-phase studies: response rates somewhere between 10% and 20% for various cancers, small cohorts, highly selected patients, good performance status. The results were interesting and, as they say, hypothesis-generating. I knew the data already.


The mythology around going down fighting remains omnipresent, a false ideal romanticized in the celluloid imagery of countless war movies and the commentary of losing football teams.
— Catriona M. McNeil, MBBS, PhD, FRACP

“Pete would like to try the PD-1 drug,” said Amy. “It is his only chance. We will pay for it. We don’t care how much it costs.”

I looked at Pete. His eyes had remained closed since the pilot faux pas. Beads of perspiration had settled on the ridges of his forehead. Nasal-prong oxygen hissed quietly in the background. An examination would later reveal a tender craggy liver, the Technicolor bruising of anticoagulation, and edematous extremities leaking into a morass of increasingly sepia-colored bedclothes.

“Do you have any pain, Pete?” I asked. A review of the medical record had revealed refusal of his regular pain relief overnight.

“It’s okay. I don’t want to get too dependent on the morphine.” Pete kept his eyes closed.

“I think before we do anything, we should sort out your symptoms and ask the palliative care team to see you,” I said.

Amy interrupted. “We already had palliative care linked up, but we don’t really need it. We are not going to give up, so how soon can we have the PD-1 drug? What have we got to lose?”

Dilemma Oncologists Face Every Day

This story is, of course, a concoction, a patchwork of countless bedside interactions, representing the dilemma oncologists face every day. It is at once recognizable yet unidentifiable. Day to day, the faces change, as do the genders, the backgrounds, even the underlying malignancies. “Can we try this for end-stage sarcoma, perhaps?” “Pancreatic cancer?” “Mesothelioma?”

As a fellow, I learned some of the art around these delicate conversations—of the discourse surrounding the living and not the dying, of the balance between toxicity and negligible efficacy.1 I wish I could say that I applied these principles to the patient cases on which this story is based. For things seem different now. There are new drugs.

But are targeted therapeutics and immunotherapeutics really any different from cytotoxics when it comes to the heavily pretreated or poor performance status patient? Or in the situation of off-label use? The experiences at our institution and elsewhere would suggest not.2,3 And although single-agent targeted and immunotherapies have a different, if not kinder, spectrum of toxicities, the idea that any of these therapies is a silver bullet is a fallacy. Furthermore, when combination strategies are used, the military term of collateral damage springs to mind.4

As an oncologist who has stood upon the barricade of the immunotherapy revolution, I have felt the exhilaration of omnipotence, as patients who should have been dead long ago return to clinic years later and say, “Thank you for keeping me alive.” And yes, in my intoxicated state, I have waved the flag of medical progress. I have given presentations peppered with hyperbole, such as game-changing, breakthrough, and paradigm shift. It is little wonder then that patients trawling through media releases on their home computers, Internet literate yet unable to critique or contextualize the information they encounter, conclude that these new drugs offer benefit and perhaps cure.5

For oncologists facing desperate patients and their families, it seems easier to embark on some ill-fated folie à deux. “Perhaps they will be one of the lucky ones.” Those able to scrape together the thousands of dollars required for a few doses of off-label drug are now demanding access, regardless of whether there is any real likelihood of success. And for those patients accustomed to a socialized medical system, the very fact of having to pay substantial sums for treatment is changing the dynamic between physician and patient. “We will pay for this medicine, and because we will pay for it, you will give it to us.” The oncologist is seen as a mere functionary, mediating some transaction between drug company and patient. Meanwhile, hospice discussions are brushed off, palliative care nurses are turned away at the door, and we watch helplessly the inevitable decline and the revolving door of admit, discharge, admit, discharge, admit.

Confronting Our Mortality

It is difficult to navigate a humane way forward. The literature regarding quality of care clearly lists chemotherapy and recurrent admissions in the few weeks before death as indicators of a job badly done,6 whereas use of palliative targeted therapy in the last month of life has raised the question of whether such treatment might compromise or delay appropriate palliative care near the end of life.7 And yet, the mythology around going down fighting remains omnipresent, a false ideal romanticized in the celluloid imagery of countless war movies and the commentary of losing football teams.

It is interesting to note that there are several simultaneous and perhaps divergent discussions occurring in the medical, legal, and ethical literatures that seek to address what is essentially our common and often existential fear of death and suffering. At one extreme of the conversation is the dialogue concerning physician-assisted suicide; seemingly diametrically opposed is the discussion around the right to try unproven therapies.8,9 In reality, both discussions are reflections of our inability to confront our mortality and find dignity and purpose at the end of life.10

There is no easy way to come to terms with the death of a younger patient. There is nothing that can be rationalized in the demise of someone with his or her whole life ahead, with a bedside decorated in crayon drawings proclaiming, “I love you, Dad.” And there is a temptation to subject the young to much more aggressive therapies, even if futile. But beyond futility, there is the truthful answer to the question “What have we got to lose?” ■

References

1. Harnett PR, Moynihan TJ: “But doctor, what have I got to lose...?”. J Clin Oncol 19:3294-3296, 2001.

2. Lomax AJ, Beith J, Bhadri V, et al: Outcomes of patients with non-melanoma solid tumours receiving self-funded pembrolizumab at Chris O’Brien Lifehouse. Intern Med J 46:1392-1398, 2016.

3. Wong A, Williams M, Milne D, et al: Performance status as a predictor of response to anti-PD1 for advanced melanoma. 2016 Medical Oncology Group of Australia Annual Scientific Meeting.

4. Niraula S, Seruga B, Ocana A, et al: The price we pay for progress: A meta-analysis of harms of newly approved anticancer drugs. J Clin Oncol 30:3012-3019, 2012.

5. Davis C: Drugs, cancer and end-of-life care: A case study of pharmaceuticalization? Soc Sci Med 131:207-214, 2015.

6. Earle CC, Landrum MB, Souza JM, et al: Aggressiveness of cancer care near the end of life: Is it a quality-of-care issue? J Clin Oncol 26:3860-3866, 2008.

7. Soh TI, Yuen YC, Teo C, et al: Targeted therapy at the end of life in advanced cancer patients. J Palliat Med 15:991-997, 2012.

8. Gopal AA: Physician-assisted suicide: Considering the evidence, existential distress, and an emerging role for psychiatry. J Am Acad Psychiatry Law 43:183-190, 2015.

9. Cohen-Kurzrock BA, Cohen PR, Kurzrock R: Health policy: The right to try is embodied in the right to die. Nat Rev Clin Oncol 13:399-400, 2016.

10. Gawande A: Being Mortal: Medicine and What Matters in the End. London: Profile Books, 2015, pp 171-172.



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