January, 2018

The Year In Rear View

By Michael J. Katin, MD

It is remarkable that the year 2017 has already come to an end. This was a year which earned the designation of the Year of the Resistance, the International Year of Sustainable Tourism for Development, the Year of Milk Tea, and, most importantly, the Year of Chatbots. What happened in oncology, or even medicine in general, to distinguish this year?

Buckminster Fuller originated the concept of Knowledge Doubling time, going from 1800 years to get from the amount of knowledge in 100 BC to the year 1700, 10 years from 1970 to 1980, and less than 12 months (and decreasing rapidly) currently. This is in contrast to the number of cat videos, which doubles every 14 minutes. A decreasing doubling time in knowledge Is much better than for PSA, and this means that our ability to deal with cancer has probably changed dramatically in the past year....well, at least in some ways. What were the ten biggest developments in oncology this past year?

Multiple news articles were released, followed by a rise in Spectrum Pharmaceutical stock, about the success of an EGFR inhibitor, poziotinib which had been rediscovered as a treatment for a subset of non-small cell lung cancer after it had previously not been effective against small cell lung cancer. Granted, this was only for a subset with EGFR exon 20 insertions, making up two percent of all non-small cell lung cancers, but two percent of a large number can still be a large number (2% of 80-85% of 222,500 ) and probably much better than the chance of winning the lottery. As if that weren't good fortune enough for the Spectrum Pharmaceutical company, it may also be effective in patients with metastatic HER-2 positive breast cancer who have already progressed despite at least two previous anti-HER-2 directed treatment programs.

Another blockbuster discovery is that a PARP inhibitor, olaparib, may be more effective than chemotherapy in with patients with advanced HER-2 negative and germline BRCA-positive breast cancer. Again, this represents a small percentage of a large number of patients, but expands the recognition of the value of PARP inhibitors, possibly for other types of cancer as well, including types of ovarian cacer, prostate cancer, and pancreatic cancer. When a major article about this comes out in research publication, Forbes,, there must be something going on.

For patients not fortunate enough to have a rare but responsive tumor type, as of the end of 2017 availability of medical marijuana has become a reality in 29 states plus the District of Columbia. Now that the majority of states allow marijuana as therapy, one can refer to the January, 2017, publication of the National Academies of Sciences, Engineering, and Medicine, The Health Effects of Cannabis and Cannabinoids, with the conclusion that there are no known therapeutic benefits but further research is needed. This would be at odds with other expert evaluations, but, fortunately, the conflict will have its denouement in the upcoming (although, of course,it would have to be) May, 2018, column.

Immune checkpoint inhibitors were again a big topic in 2017, particularly with no fewer than four drugs in this category approved by the FDA for use in treating urothelial carcinoma -- atezolizumab, avelumab, durcalumab, and pembrolizumab. Increasing approval of drugs in this category appears probable, also increasing stress on pharmaceutical companies and focus groups to come up with catchy proprietary names for them.

Recognition needs to be given to a major advance in quality of life maximization, published in the August 1, 2017, issue of the International Journal of Radiation, Oncology, Biology, and Physics. This randomized phase II study clearly demonstrated a benefit to the yoga vs. no yoga group of patients at the University of Pennsylvania undergoing external beam radiation therapy for treatment of carcinoma of the prostate, with many of these also receiving androgen deprivation therapy. Sixty-eight patients were willing to be randomized, and 35 were randomized to yoga twice a week and 33 to no yoga. Thirteen of the 35 did not go ahead with the yoga program and 5 of the 33 dropped out of the no yoga program (????). Only 17 of the remaining 22 attended more than 70 per cent of the sessions. The type of yoga was Eischens yoga, previously known as High Energy Yoga. This would seem pertinent, since the patients were treated with high energy x-rays or protons or both. Those who finished the program (only a cynic would say the best conditioned patients had self-selected) had a decrease in cancer-related fatigue and stability of erective dysfunction scores compared to the no yoga group. This clearly mandates the need for yoga sessions to be a part of all radiation therapy courses. It is also to be noted that a man seeking the title of "world's oldest man" attributes his being 120 years old to yoga....and two other things.

In June, an abstract presented at the Annual Meeting of the American Society of Clinical Oncology changed management of patients with advanced prostate cancer. The Systemic Therapy of Advancing or Metastatic Prostate Cancer (STAMPEDE ) study documented improved overall survival and failure-free survival in patients who received abiratirone and prednisone at the start of androgen deprivation therapy compared to those with androgen deprivation therapy alone. Ironically, while newly-created pharmaceuticals dominated the presentations, it was a drug, derived from ketoconazole, that has been around since the early 1990s that might have the biggest impact on the largest number of patients.

Perhaps an identical impact was made by the statement by the American Society of Clinical Oncology on November 7 that alcohol consumption is bad. In an era in which "medical marijuana" has been accepted as a tool for management (can't wait to see the May, 2018, column!) it is now indicated to deprive everyone of alcohol because of risk of causing cancer and also interfering with treatment. Of special interest is ASCO's comments against "pinkwashing," the practice of advertising products such as alcohol while displaying pink ribbons to show solidarity with breast cancer research and support organizations. Presumably Pabst Beer is still safe.

What should have been the most important development of 2017 has seemed to vanish from view. In May it was reported that a byproduct in the production of Trump Wine, trumpotinib, was capable of producing complete remission in 98% of all types of cancer. This information was briefly carried on Breitbart and not mentioned at all by the AP, CNN, NBC, CBS, or MSNBC. Further studies are planned through Trump University, with attempts to control the major side effects of excessive hair growth and shrinkage of distal appendages.

In the meantime, cancer research otherwise progresses at a speed which is impressive but still not as rapid as we would like. As if to call attention to this, a publication in February described the role of Snail, otherwise known as zinc finger protein SNA/1, in allowing cancer cells to switch between aerobic glycolysis and the pentose phosphate pathway in order to escape damage from treatment and metabolic stress in general. If that weren't enough, Slug (SNAI2) is a similar protein which can protect cancer cells. The obvious puns will be avoided but perhaps this explains why the snails and slugs in the research community have not made more progress.

Finally, there is the topic that has been ranked as the #1 oncology advance of 2017 in every survey up until this one. When an unemployed T cell is suddenly transformed into a Chimeric Receptor Antigen T cell it now has the ability to attack anything with that particular antigen. In August, the FDA approved this method for treatment of relapsed or refractory B cell precursor acute lymphoblastic leukemia, given the name Kymriah (tisagenlecleucel). A huge number of articles in the media followed, without reference to the fact that Provenge (sipuleucel-T), sensitizing antigen-presenting cells (APCs) to prostatic acid phosphatase antigen to then present (hence the name) this to T-cells, had been approved in 2010. Interestingly, in August Besponsa (inotuzumab ogozamicin) was also approved for this indication. To this date there have not been any protocols launched for combined treatment with tisagenleleucel and inotuzumab ogozamicin although the havoc this would wreak with spell check systems would be phenomenal. The CAR T Cell therapy technique has achieved public awareness and is being promoted as the potential cure for all types of cancer beyond B-cell ALL, and whether this materializes does not minimize the this is the most popularly recognized cancer treatment development and worthy of the designation Magna.

Now, on to 2018. It has been designated by the United Nations as the International Year of the Periodic Table of Chemical Elements. CoUld thiS Be tHe YeAr of eveN BiGgEr dIScOVErIEs? I HaVe a PReMoNiTiON It Will.

Emanuel Countdown: Dr. Ezekiel Emanuel's biographies list his birth year as 1957 but, interestingly, do not list a birth date. He has expressed that he does not wish to live past his 75th birthday. Giving him every benefit of the doubt, he will have his 75th birthday no later than December 31, 2032. Including January 1, 2018, this leaves 5,479 days to his goal.