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Last Month in Oncology with Dr. Bishal Gyawali: January 2018

CONCORD shows Discordance in global cancer outcomes
The CONCORD Working group has published the global surveillance of trends in cancer survival for 18 common cancers from 322 population based registries in 71 countries between 2000-2014. Although the reliability of population based cancer registries in some of these countries can be questioned, the huge gulf in cancer outcomes between high income and low-and-middle income countries is beyond any doubt. It is unacceptable that in modern times, for all the talk of personalized therapies and moonshots, cancer survival rates are determined more by where a patient lives.  So the important question is: how do low and middle income countries bridge the gap? Of course, not by spending the limited resources in cost-ineffective interventions or copy-pasting what high income countries have done, but by working more on "cancer groundshot" approaches of which one of the first steps would be to develop a reliable population cancer registry that provides much needed data such as these for policy planning.

High time for HIPEC
The efficacy of intraperitoneal chemotherapy in ovarian cancer is not news. In this important study from the Netherlands, the investigators studied whether the addition of hyperthermic intraperiotenal chemotherapy (HIPEC) to the interval debulking surgery would improve outcomes in stage III ovarian cancer. The results are satisfying with the addition of HIPEC showing nearly a year of improvement in median overall survival, something we very rarely see in oncology. This advantage was achieved without any increase in side effects and a median of 2 more days in hospital. Health related quality of life didn't differ.  Sounds to me like exciting news in ovarian cancer, but the accompanying editorial is unusually pessimistic for NEJM. I can only imagine the noise, hype and optimism if this same advantage was shown by a drug called hipecizumab rather than HIPEC. Indeed, introducing HIPEC into routine care needs expertise and research building. So it might take a good amount of time before HIPEC gets introduced in LMICs like Nepal, but you know, a patient with ovarian cancer in Nepal can easily get bevacizumab if she is able to afford it (a course of bevacizumab in Nepal costs around $1000, Nepal's GNI per capita is $2520). Ultimately, it's a question of setting national priorities and agendas.

Gamechanger or just bankruptcy inducer?
A drug called brentuximab vedotin that costs more than $20k a month was tested in a phase 3 trial among patients with stage III-IV Hodgkin's lymphoma as first line therapy as a replacement for bleomycin in the ABVD regimen. A AVD (brentuximab) regimen provided similar overall survival to ABVD (bleomycin). Brentuximab is already approved for relapsed disease. Further, based on PET scan after 2 cycles, patients were allowed to change therapies for inadequate response. Surely, brentuximab doesn’t have the pulmonary toxicities that bleomycin is notorious for and thus might represent a good option for patients with preexisting lung disease and able to afford but the study claims that A AVD is a better regimen than ABVD  because the modified progression free survival ( an unvalidated surrogate endpoint used as the primary endpoint for this study and defined as the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) was slightly better (4.9% difference in 2 year modified PFS rates, HR 0.77, p =0.04). So without any improvement in OS and some improvement in an unvalidated surrogate, can A AVD be considered the new standard of care , especially considering higher rates of neutropenia, febrile neutropenia and peripheral neuropathy with brentuximab although with a lower pulmonary toxicity? Oh, how much I wish they actually collected and reported the quality of life data!

We have known for some time now that RECIST is not a good metric to evaluate response with immunotherapies in cancer. This new study shows that some patients may benefit with continuation of immunotherapies beyond progression, but a better conclusion would be that RECIST is not a good metric for immunotherapy. Also, the problem with using immunotherapies beyond progression is when do we stop? Search for a better response criterion and reliable predictive biomarkers are the billion dollar questions in immuno-oncology.

Over use of diagnostic modalities
Cancer recurrence is terrible, and naturally, everyone wants to detect the recurrence as early as possible. Hence, zealous use of imaging and tumour markers is common during follow up after primary treatment of cancer. In many cases, however, these are just expensive and futile exercises because either the modality doesn't detect early recurrences more than the standard follow up or that the early detection doesn't necessarily lead to better outcomes. We have already known that CA-125 and CT surveillance didn't improve outcomes in follow up of ovarian cancer. Last ESMO, we saw that frequent CT scan of lungs during follow up after surgery wasn't necessary. Now, a new study has shown that regular 6 monthly PET scans had no value to detect recurrence of colorectal cancers after curative surgery. Honestly, I have never recommended any patient for regular PET scans to detect colorectal cancer recurrence, but if there are some big fans of PET scans, please don’t use this expensive luxury during follow up after colorectal cancer surgery.

Let me take selfies
In our editorial published in ecancer last month, we ask if the oncology community has a rejection bias against repurposing drugs in oncology. Taking three case examples, we show that for similar results in trials by a repurposed and an expensive drug, the oncology community treats the expensive drugs favourably while the repurposed drugs are immediately rejected. We argue that all drugs should be held to the same standards.

In another study published in JAMA Oncology, with the help of meta-analysis we show that even in the modern era of novel agents for multiple myeloma, autologous stem cell transplantation remains the preferred therapy in transplant-eligible patients.

Some other mentions

  1. This study with probably the most expensive regimen one could ever think of in breast cancer showed that the use of pablociclib fulvestrant trastuzumab pertuzumab decreases…… the Ki-67!
  2. Speaking of trastuzumab, a new study has proven the equivalence of a new trastuzumab biosimilar to the original molecule. Having more biosimilars is welcome as we assume this will lead to competition and price reduction, although some recent trends have dampened the enthusiasm. Surely, there is no point in having a cost-similar biosimilar.
  3. Immune checkpoint inhibitors have now been approved in a variety of cancers with varying efficacy. However, these new class of drugs have a different side effect profile and managing those toxicities isn’t always easy. So this timely review on toxicities of checkpoint inhibitors and their management is very handy.

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.



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