My Liver Cancer Blog

Hat tip to my husband for the title of this post. Each time I go get an infusion it does feel like I have to summon all my gumption and grit and fortitude. Not that it’s been awful. In fact, the worst part of the zenocutuzumab treatment is the infusion of Benedryl I have to have to prevent possible allergic reactions to the Zeno (e.g. very rare but possible is pneumonitis, a swelling and inflammation of lung tissue). The Benedryl makes me so antsy that I feel like I’m crawling out of my skin and need to move around, which is impossible when you are hooked up to an infusion machine. But, even though the infusion experience is totally fine, each time it still feels like I need to gather my courage to make myself go up that elevator, into that room, and sit my butt on that chair.

Only to be spit back out! By which I mean, Provis, the private infusion clinic I’ve been going to for the Zeno, is closing. Is, in fact, now closed. (As I say to my husband in my more cynical moments, “It wouldn’t be Canadian cancer care if there wasn’t something. There’s always something..”) It’s a private business, after all, with no obligation to stay open or to provide a service. And the owner is retirement age and has run the clinic for 21 years, and they were raising the rent on his space, and much of his business now was iron infusions (not oncology-related infusions), and there are now too many other private clinics offering iron infusions. (Why iron infusions when patients should be able to receive these free of charge from a public hospital? Because of months-long wait lists, apparently. https://careand.ca/blog/iron-infusion-toronto-cost-ohip-coverage)

So, yesterday was my final infusion there. I was their very last patient. (My infusions take much longer than iron infusions, so I’ve been the first to arrive and the last to leave each time). In fact I think they kept the clinic open until yesterday specifically so they could give me my infusion because otherwise they would have one dose of Zeno left in their fridge, and they would have to give me back $36,000.

I can’t say I was surprised by the closing of the clinic. I had been quietly wondering when it might happen. I could see it in the owner’s eyes that this was coming. And, of course, the clinic was only open on Tuesday afternoons, which I imagined was not the case in its hayday. What did take me by surprise was the short notice about its closing. We arrived for an infusion 2 weeks ago, and were told that the next infusion would be the last. So now it’s a bit of scramble to transition to a new private clinic, Inviva, especially nerve wracking since ordering the Zeno from the US has been a somewhat complicated process, and so the order basically needs to be put in now, today, for it to arrive in time for my next dose two weeks from now. But, with this new clinic, which is owned by McKesson, the largest pharmaceutical distributor in Canada, I get a “patient navigator,” and so for the first time I feel like I don’t have to deal with these problems on my own. I don’t have to be the person sending 10 emails a day trying to figure out who is now responsible for ordering the drug and trying to get them to confirm that they have done so. So far my patient navigator seems to be on top of it, and he assures me that everything will be in place for my next dose on Aug. 5. Cross your fingers for me that the transition is smooth.

But back to my last day at Provis and the situation that is very like mine, but made me even more furious than my own situation. I was the first patient there. They were only expecting 5 patients, and I could see from reading the list upside down that all of them were receiving cancer-related infusions. (Yes, you come to be able to recognize cancer-related drug names, even if they aren’t for your kind of cancer, and yes, you are absolutely right that I should not be reading a list of patients and their treatments, whether it is upside down or not. But they shouldn’t leave it lying on a desk like that.) I snagged my favorite infusion chair (it reclined more than the others) and got myself situated for the infusion (iPad, headphones, blanket, and slippers all at hand). I suddenly realized that the second patient to arrive was speaking loudly from across the room, trying to get my attention. I’d seen her come in. She was very thin, frail-looking, arrived in a wheel chair and with an oxygen tank. Her husband was with her, and she was a bit snappish with him. I couldn’t tell whether this was the nature of their relationship or if pain and discomfort was making her dissatisfied with everything he did and said to try to help her.

Patients pretty much never have conversations. Maybe we share a laugh or exchange glances if a nurse says or does something funny, but the chairs are too far apart for chatting, and everyone is on their phone or iPad anyway. And a few people nap. So at first I didn’t realize this patient was trying to talk to me. But I wasn’t hooked up yet, so I went over to her chair. And she launched immediately into her story. Which was that she was a non-small cell lung cancer patient who had gone through chemotherapy, and then moved on to a targeted therapy, which had been working well, but then stopped working. So her oncologist took her off it, and taking her off it had what she called a “boomerang effect” — the cancer came back worse than ever. She lost her appetite, she lost a lot of weight, and breathing became more difficult, necessitating the wheel chair and the oxygen tank. “A month ago I wasn’t like this. I didn’t need all this,” she said. So now her oncologist had put her on a different targeted therapy, “even more precise to my cancer,” she said. (This made me wonder if her previous treatment was, in fact, a targeted therapy because I haven’t heard one targeted therapy being described as “more precise” than another. Each one is targeted to a specific mutation. But anyway…)

This new targeted therapy, she said, was approved for breast cancer in Canada, but not approved for non-small cell lung cancer. Thus, she was paying for it herself and receiving it at the private infusion clinic. The tumor mutation — HER2 — is the same in both cancers, but the targeted therapy that treats it, Enhertu, would be covered in Ontario if she had breast cancer, but is not covered because she has lung cancer. This is crazy. First, I’ve looked up the efficacy of Enhertu for lung cancer patients with HER2, and it has a 50% response rate and a median progression-free survival of 10 months. (These are great numbers for targeted therapies). Second, Enhertu was approved for non-small cell lung cancer patients with HER2 mutations in the USA in 2022, in Europe in 2023, and in Australia in 2025. Non-small cell lung cancer is the most common kind of lung cancer in Canada — there are approximately 27,000 new cases each year (comparatively, there are approximately 500 new cases of cholangiocarcinoma in Canada each year). Only 3% of those cases will have the HER2 mutation, but that’s still 800 patients per year that could benefit from Enhertu.

Patients in the UK are in the same situation – Enhertu is approved for breast cancer, but not for lung cancer. In both cases, the manufacturer has declined to apply for approval. So who to blame in this situation – the manufacturer or the country? The country can’t approve the drug if the manufacturer doesn’t apply, but the manufacturer has declined to apply because the regulatory bureaucracy is too onerous, and in both cases they worry they won’t pass the cost-effectiveness test or that the time to approval will take too long. Meanwhile, Europe recently approved Enhertu as a “tumor agnostic” drug – meaning that it doesn’t matter what kind of cancer you have. If your cancer has the HER2 mutation, and you have experienced disease progression after first-line therapy, you are eligible for Enhertu.

So, I find myself infuriated again. At least in my situation I kind of understand why the manufacturer won’t seek approval in Canada: given the very small number of cases of cholangiocarcinoma per year, and the 1% of these that will have the NRG1 fusion mutation, there would probably be 5 patients per year who might benefit from zenocutuzumab. And maybe only 2 or 3 of these would even know they could benefit from the drug because the other 2 or 3 will never get the thorough genomic testing they would need to identify the mutation. And, given the current price, provinces would never adopt it for their formularies even if the drug were approved at the federal level. So, it’s not worth it to the company to bother. But Enhertu has clear benefit for a significant number of lung cancer patients. The only thing that makes this situation somewhat acceptable in my opinion is that the manufacturer is AstraZeneca, and they do have a compassionate use program, so possibly the patient I met is paying a reduced amount for her treatment. And I looked up common mutations for non-small cell lung cancer, and targeted therapies are approved for all 5 or 6 of them in Canada and have been adopted by provincial formularies. Still, I am convinced that the future of cancer care is precision oncology – therapies that are specific to tumour mutations. How and whether Canada’s regulatory apparatus will come to terms with this future remains to be seen.