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    From research to clinic

8 Gennaio 2019

From research to clinic

Prioritization in oncology: going global before going to the moonBishal Gyawali – [Read the italian version]

Prioritization in oncology: going global before going to the moon

Bishal Gyawali, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School.

La Terra vista dalla Luna

In theory, the concept of prioritization must be the most “common sense” approach to any public policy, including health but several real life examples show that this simple concept has often been ignored, sometimes with disastrous consequences to public health and economy. Being an oncologist, my examples will be more cancer specific but I am sure that the audience can draw similar conclusions across the health-care system.

Most of us are aware of the many “cancer moonshot” campaigns launched in the US and other similar campaigns in some high income countries focusing on artificial intelligence, big data, genomics and other modern interventions-none of which have evidence of saving lives- while very few funding, if any, is available to implementation of strategies that we already know to work well. For example, rather than focus on cervical cancer screening and HPV vaccination which would help eliminate cervical cancer, we are more focused on finding new genomic targets of advanced cervical cancer with the hope of targeting it with a modern therapy that will improve the survival by a couple of months. Common sense dictates that the priority should be the other way round-to focus more on implementing high value interventions that achieve cure than to chase marginal gains at high costs. I call this “cancer groundshot” approach which will probably save more lives at a fraction of the cost of “cancer moonshot” and is a nice example of the need to realign our priorities [1].

Sadly, most LMICs don’t have access to curative cancer therapies such as surgery or radiotherapy. I recently read a news in BBC which showed that there were fewer radiotherapy machines for people in Nigeria than they had for dogs in US [2]. But then, I also read a journal article about the use of Watson for Oncology in another LMIC India [3]. While there are many people without access to basic surgery in India [4], focusing on artificial intelligence seems not only a lack of prioritization but also an example of waste especially given the fact that there is no data to suggest that AI improved outcomes even in any HIC [5].

We also seem to have forgotten our priorities in treating cancer patients, and thereby our priorities in trials and approvals of cancer drugs. Why does a cancer patient accept to take a cancer drug that comes with numerous toxicities? The patient ideally wants to have a longer as well as better life as a result, or at least either one of them if not both. That’s the ground reality. Whenever I prescribe an anticancer therapy, I believe the drug will make patients live longer or feel better so that the toxicities are worth the benefits..but do these drugs actually make patients live better and/or longer?

A 2017 study showed that most trials leading to drug approvals don’t use survival or quality of life endpoints but surrogate endpoints such as response rates or PFS [6]. A 2015 systematic review showed that the correlation of these surrogate endpoints with OS was low-moderate for most settings [7]. So most cancer drugs don’t seem to improve survival. But do they improve quality of life? This is an important question that we tried to answer in our recent study. Of the 352 phase 3 RCTs published in topmost journals, nearly half didn’t include QoL as an endpoint, of those that did a quarter didn’t report on QoL despite it being an endpoint and finally, the correlation between positive QoL and positive PFS was poor [8]. No wonder we don’t have a single drug approved on the basis of improved QoL.

This begs the question what exactly are we achieving from these drugs if we don’t know that they are improving lives quantitatively or qualitatively. Shouldn’t we be asking more from these drugs that are both financially and physically toxic? Speaking of toxicities, our recent work also showed that most trial publications falsely downplay toxicities of cancer drugs [9]. This looks alarming, but again when we look at our priorities we find the answer. Because the trials are conducted by the industry that can literally make millions of dollars from a single blockbuster cancer drug, we can’t act surprised when they use surrogate endpoints, don’t report quality of life or downplay the toxicities. The only mechanism to put some control here is regulatory approvals, but we see that the recent trend is to rather lower the bar and approve more and more of these drugs based on lower bars for efficacy. The priority is neither efficacy nor safety, but speed of approval. Sure, cancer patients want drugs fast but do they really want unhelpful and toxic drugs fast?

The issue of cancer drugs has now become not only a public health issue but also an economic one. Cancer drugs are one of the most expensive drugs we have with average monthly cost of cancer drugs in US now around $15,000 [10]. Shouldn’t we be asking more from these drugs rather than just improving some tumor size?

References

[1] Gyawali B, Sullivan R, Booth CM. Cancer groundshot: going global before going to the moon. Lancet Oncol 2018;19:288-90.
[2] Do US dogs have better access to radiotherapy than Nigerian people? Bbc News, 12 ottobre 2017.
[3] Somashekhar SP, Sepúlveda MJ, Puglielli S, et al. Watson for Oncology and breast cancer treatment recommendations: agreement with an expert multidisciplinary tumor board. Ann Oncol 2018;1;29:418-23.
[4] Roy N, Khajanchi MU. A hospital too far – access to surgical facilities in India. Lancet Glob Health 2015;3:e587-8.
[5] Gyawali B. Does global oncology need artificial intelligence? Lancet Oncol 2018;19:599-600.
[6] Davis C, Naci H, Gurpinar E, et al. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13. BMJ 2017;359:j4530.
[7] Davis C, Naci H, Gurpinar E, et al. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13. BMJ 2017;359:j4530
[8] Hwang TJ, Gyawali B. Association between progression-free survival and patients’ quality of life in cancer clinical trials. Int J Cancer 2018; Oct 29.
[9] Gyawali B, Shimokata T, Honda K, Ando Y. Reporting harms more transparently in trials of cancer drugs. BMJ 2018;363:k4383.
[10] Harding A. As cancer drug prices climb, value not keeping pace. Reuters, 12 aprile 2018.

december 2018

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