She is grunting from the work of breathing. Perched at the edge of a chair, she hunches over her walking frame in order to find a comfortable position to speak the few sentences she can manage. Having watched her decline, I estimate she has weeks to live. Slowly and painstakingly, she removes a paper buried in her bag. I can’t help noticing that this task consumes so much of her energy that her son has to unfold the newspaper article.
“This immune medicine, can I get it?” she huffs.
“I’m afraid not.”
“But it looks amazing!”
“It’s not quite the miracle cure it’s made out to be”, I say and watch her face crumple in disappointment. I wish I didn’t feel so bad for telling the truth. This is the moment she will remember when I extinguished her hope. She accepts my lengthy explanation but the next patient refuses, insisting that I either prescribe him immunotherapy or find someone that will. His liver is failing and his blood sugars are wildly abnormal — even if there were a trial available, he would not meet the strict entry criteria. Yet, feeling foolish, I make a round of calls to ease his concerns. Everywhere, the answer is the same — there is no evidence to treat his cancer with immunotherapy and even if there were a trial available, he would not qualify. Unfazed, he finds an oncologist willing to prescribe him the drug so long as he self-funds it. Some weeks and many thousand dollars later, the patient dies amid a storm of side effects unleashed by the new drug. Tragically, the unconventional toxicities go initially unrecognised, adding to his suffering. When his wife rues his inability to accept his mortality, I remind her that he was not the first patient to take the battle metaphor to heart.
Every oncologist recognises the eagerness of patients to access immunotherapy, the latest class of anticancer therapy to make their mark. After all, barely a week passes without another account of this revolution in cancer.
The immune system defends the body from all sorts of attacks. It’s the reason why cuts heal, colds improve and a myriad other bodily threats are neutralised without us even knowing. But powerful brakes also prevent the immune system from attacking normal cells and causing unwanted damage. Cancer cells cleverly manipulate these same brakes to evade recognition by the immune system. Very simply, immunotherapy drugs release these brakes, instigating immune cells to attack and destroy cancer. The process is as elegant as it is fascinating and I will never forget being in the crush of oncologists who turned up for long-forgotten immunology lectures when these drugs first captured our imagination a few years ago.
In clinic, facing a patient who wants “everything done”, it’s hard not to be seduced by the promise of immunotherapy, exalting at the hostage turned avenger. It can’t hurt to try, the desperate patient pleads, and it’s tempting to further that hope with the rejoinder, “you’re right, what’s there to lose?” But the very next week you discover just how much there is to lose when the emergency doctor calls with panic in her voice.
The beauty of immunotherapy is that some patients experience an impressive, even a lasting response. For the doctor and patient exhausted by the search for options, the sight of melting tumours can feel almost ecclesiastical. Immunotherapy provides good reason for optimism and even awe, but what it is not is a panacea. Unfortunately, it does not work in the majority of patients. Studies show a response rate of roughly 20%, with a variable survival benefit. Some patients get to live long and productive lives but many don’t. Frustratingly, immunotherapy works well in some cancers and not at all for others and we are still finding ways to distinguish the two.
Chasing another elusive cure
Meanwhile, an immune system gone awry poses serious consequences for organs, including the liver, lungs, heart, bowel and vital glands including the pituitary and thyroid. These organs can develop severe, even fatal inflammation, with two-drug combinations proving particularly toxic. Patients can quickly go from feeling okay to being profoundly unwell — and since the side effects are as novel as the drugs, they may not be quickly identified or treated in many places. To deliver immunotherapy safely means having not only oncologists but also a range of other specialists ready to anticipate and treat serious toxicities. This infrastructure has been slow to come together, with doctors and patients learning tough lessons simultaneously.
In medicine, choosing the right patient is as important as selecting a great drug. Over a thousand immunotherapy trials are under way but researchers fear that they are fuelled less by promising evidence than by the urgency of drug companies to produce the next blockbuster. Duplicated and wasted efforts aside, oncologists are realising that sidestepping the discussion about financial toxicity is becoming harder in an era where cancer treatment can cost more than a house.
In clinic, it’s poignant to witness terminally ill patients hold out for the magic of immunotherapy. They vex over how to qualify for it, where to find it, and how to afford it. Loved ones find themselves caught in a bind when they sense the end of life but the patient does not. Ultimately, chasing after yet another elusive cure deprives many patients of precious time to confront their mortality. The existential questions that weigh on us all are given a wide berth again in the hope that a new day will bring a new drug. Broaching end of life care can feel at odds with the rosy promise of immunotherapy. Patients feel aggrieved that they have been “denied” immunotherapy but what they and their loved ones actually end up losing is the opportunity for sensitive discussions about palliative care, emotional welfare, and all the other things that matter when cure is not possible. How to do both well is an ongoing challenge for oncologists.
The good news is that the advent of immunotherapy has undoubtedly changed the landscape of cancer medicine. The curiosity and enthusiasm are well deserved. Thanks to the dogged determination of scientists, we can dream of a day when such therapies will be available, affordable and safe not just for the exclusive patient, but sufferers all over the world. But for now, immunotherapy is not, and should not be portrayed as, a miracle cure for the vast majority of cancer patients. Instead of nourishing hope, the hype destroys it.
It is entirely understandable that vulnerable patients want to leave no stone unturned in the quest for cancer treatment. But the responsibility belongs squarely to oncologists to balance hope with reality, and the media for resisting the pull to illustrate a complex, nuanced and often sad situation with breathless stories of miracle cures. There are many more stories of immunotherapy to be told but in telling them, our common mission ought to be primum non nocere — first do no harm.
— Guardian News & Media Ltd
Dr Ranjana Srivastava is an oncologist and an award-winning author.
