Last Month in Oncology with Dr. Bishal Gyawali: October 2017

2 Nov 2017
Last Month in Oncology with Dr. Bishal Gyawali: October 2017

Why should you be interested in global oncology?

This was one of the questions a participant asked at the 2nd Royal Society of Medicine meeting on cancer control in low-and middle-income countries. Why should I, someone from a HIC, be interested in cancer control in LMICs? The answer seems obvious to us working in global oncology/global health and the question might seem stupid to some; but in today's world of "stupid is wise, narrow is wide", I guess it is important to state the obvious. In October, there were a couple of important publications that directly addressed this question. One is a rather technical report published in NEJM, but the other, published in JAMA, is an emphatic personal story from an oncologist who has left the luxuries of US life to make a difference in cancer care and research in Malawi, Africa. The JAMA piece is a must read for everyone, irrespective of your interest in global oncology. But here comes the embarrassing part: this powerful answer to "global health: what's in it for us?" is behind the paywall at JAMA!

If you gather enough interest in global cancer care by reading these pieces, the question that comes to mind is: so how? How can we improve cancer care in LMICs? What can we do? What's the way forward? The way forward, in my opinion, is to focus on what I call the "cancer groundshot" where we invest on implementation of knowledge we already know works, as well as co-developing cheaper innovations locally that are of equal importance to HICs. I have talked about this in detail in this interview, in case you are interested.

This point was also poignantly made in this Nature commentary appropriately titled "Cancer patients need better care, not just more technology" to which we have added "Cancer care: Tap latent source of frugal cancer ideas". 

Hidden in plain abstract

Follicular lymphoma is a relatively indolent lymphoma, the treatment of which has been transformed with the introduction of rituximab. In a phase 3 trial, a newer anti CD-20 antibody obinutuzumab was compared versus rituximab during induction as well as 2 years of maintenance in patients with follicular lymphoma. Conclusion: obinutuzumab improved PFS versus rituximab. The results section of the abstract reveals that the 3 yr PFS rate was higher with obinutuzumab (80% v 73.3%, HR 0.66, p = 0.001), but so were severe adverse events (74.6% v 67.8%), serious adverse events ( 46.1% v 39.9%) and although not mentioned, cost of the drugs. What has not been mentioned at all in the abstract is the data for overall survival. Can you guess why? OS was similar for both the drugs and the Kaplan Meier graphs run nearly collinear. The 3 yr OS rates remain over 90%( 94% v 92.1%, p =0.21) . But why should they tell you that in the abstract, right?

Pitfalls of tissue agnostic approval based on response rates

In NEJM, the FDA has published a self-congratulatory piece on the cancer site agnostic approval of pembrolizumab.  Although I believe that this is an important landmark in the history of oncology and FDA approvals, certain issues deserve special mention. First, this is appropriately an accelerated approval with the intent to provide early access to drugs for people with high unmet need. But the FDA should ensure that follow up studies are duly conducted with hard endpoints and if the benefits don’t hold, take appropriate measures. This is important because this approval was based on data from only 149 patients, and only based on response rates. A look at the table shows how weak the data are: 2 out of 2 responses provide a 100% response rate for breast cancer, and 1 of 2 responses in prostate cancer patients provide a rate of 50%. Can we be confident of MSI high prostate cancer benefiting from pembrolizumab based on these data? Furthermore, the ranges for the duration of responses are very wide. So, should we be looking for a finer biomarker even within the subset of MSI high tumours? 

ATTRACTIVE? Depends on the eyes of the beholder

In the phase 3 ATTRACTION trial, the median OS was statistically significantly improved with nivolumab versus placebo as the last line therapy for gastric or gastro-esophageal cancer. Sounds attractive? The gain in median OS was only 1.2 months- patients on placebo lived for a median of 4.1 months while those who took nivolumab lived for a median of 5.3 months (HR 0.63, p < 0.0001). I am not sure that a patient with less than 6 months to live would be happy to undergo treatments and toxicities to live a month longer. 

The POINT of prophylactic antiemetics while starting opioids

The use of prophylactic prochlorperazine to prevent nausea and vomiting while starting opioids is common practice, at least in Japan as our group has previously shown. Opioid-induced nausea and vomiting (OINV) is a common problem in palliative care but without any evidence based guidelines regarding prophylactic treatment. Our group conducted probably the first phase 3 RCT (the POINT study) to test whether prophylactic antiemetic (prochlorperazine) would be effective in preventing OINV and found that it wouldn't.  So now we have evidence that it is pointless to prescribe prophylactic antiemetic to a cancer patient while starting him/her on opioids.

Cost of cancer drugs: it's not just the launch price

Most of the discussions on the high cost of cancer drugs are centered on the exorbitant launch prices the modern drugs come with. However, price hiking after the launch of these drugs is another strategy cleverly exercised by the industry that usually escapes attention. An important analysis has shown that the mean percent change in the cost for all drugs was 18%, after adjusting for inflation, and over a 8-year follow up period. Figure 1 of this paper is worth a hundred words to which I refer my readers.

Let me take a selfie

It is well known that cancer drug prices are cheaper in low and middle income countries (LMICs) compared with those in high income countries. However, it is important to emphasize that these drugs, despite being priced lower, are still unaffordable for patients in LMICs. This was recently highlighted in an important analysis which I discuss in this editorial.

Bishal Gyawali, MD, PhD completed his training in medical oncology at the Graduate School of Medicine, Nagoya University, Japan, and obtained a PhD as a Japanese government scholar. He works as a medical consultant at the Anticancer Fund, a not-for-profit organization based in Belgium as well as holding an affiliation at the Institute of Cancer Policy, UK. His areas of clinical and research interests include evidence-based oncology practice, global oncology, cancer policy, cancer management in resource-limited settings, financial toxicities of cancer treatment, clinical trial methods and supportive treatment of cancer. He has no conflicts of interest to declare. Dr Gyawali tweets at @oncology_bg. Read his previous blog posts here.