1. New England Journal of Medicine. June 23, 2022. Andrea Cercek, M.D., Melissa Lumish, M.D., Jenna Sinopoli, N.P., Jill Weiss, B.A., Jinru Shia, M.D., Michelle Lamendola-Essel, D.H.Sc., Imane H. El Dika, M.D., Neil Segal, M.D., Marina Shcherba, M.D., Ryan Sugarman, M.D., Ph.D., Zsofia Stadler, M.D., Rona Yaeger, M.D., J. Joshua Smith, M.D., Ph.D., Benoit Rousseau, M.D., Ph.D., Guillem Argiles, M.D., Miteshkumar Patel, M.S., Avni Desai, M.D., Leonard B. Saltz, M.D., Maria Widmar, M.D., Krishna Iyer, M.D., Ph.D., Janie Zhang, M.D., Nicole Gianino, M.S., Christopher Crane, M.D., Paul B. Romesser, M.D., Emmanouil P. Pappou, M.D., Ph.D., Philip Paty, M.D., Julio Garcia-Aguilar, M.D., Mithat Gonen, Ph.D., Marc Gollub, M.D., Martin R. Weiser, M.D., Kurt A. Schalper, M.D., Ph.D., and Luis A. Diaz, Jr., M.D. PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer.
Smallpox, tuberculosis and polio were once three of the most dreaded maladies facing humanity. But today, for all practical purposes, they are extinct.
Unfortunately, as vaccines and antibiotics have conquered once-deadly infectious diseases, we are more likely to encounter dementia, heart disease and cancer because average lifespan has dramatically increased.
Heart disease is becoming increasingly manageable, while dementia remains the ¡°great white whale¡± of medical research.
On the other hand, cancer represents an entirely different challenge. That¡¯s largely because it¡¯s a diverse class of diseases whose members share a few common characteristics. As such, there is no single cure for cancer, but rather sets of treatments which may be effective against one or more types.
Fortunately, just as the mid-20th century came to represent ¡°the golden age of antibiotics and vaccines,¡± the mid-21st century is likely to become ¡°the golden age of cancer treatment.¡±
Why?
Because science is finally developing a detailed understanding of the biochemical processes that trigger, promote and ultimately kill cancer cells. And this opens up paths to early detection and to turning the body¡¯s natural defenses against cancer. This enables scientists to develop highly targeted solutions that are both effective and minimally disruptive to the patient¡¯s quality-of-life.
Consider the results of a recent clinical trial of the GlaxoSmithKline drug Dostarlimab for colorectal cancer. Amazingly, the cancer vanished in every single patient! It was undetectable by physical exam, endoscopy, PET scan or M.R.I.
Dr. Luis A. Diaz Jr. of Memorial Sloan Kettering Cancer Center, who led the research said he knew of no other study in which a treatment completely obliterated a cancer in every patient. Other experts agree that this is the first documented case in the history of cancer when this has happened.
That¡¯s a big deal since roughly 150,000 Americans are diagnosed with colorectal cancer each year. And NIH estimated the annual cost at $25 billion or about $167,000 per patient. Better yet, the Dostarlimab study involved patients with a mutation called MMRD, which makes them more difficult and expensive to treat than the typical patient.
Dostarlimab is a type of immunotherapy called a monoclonal antibody, or more specifically, a checkpoint inhibitor. It works by attaching to a protein called PD-1 on the surface of cancer cells. This helps the immune system to recognize and attack the cancer. A 500mg dose of the drug is administered into the blood stream through a drip into a vein over a 30-minute period.
At current prices, nine Dostarlimab treatments delivered over 6 months costs about $100,000.
The treatment can trigger mild side-effects, including a rash, dry and itchy skin, fatigue and nausea. Three to five percent of patients taking other checkpoint inhibitors report more severe side-effects like muscle weakness and trouble swallowing. However, this is a small price to pay given the benefits recently reported in the New England Journal of Medicine.
The rectal cancer patients in the study had faced grueling treatments including chemotherapy, radiation and most likely, life-altering surgery that could result in bowel, urinary and sexual dysfunction. Some would even need colostomy bags.
Yet, for every patient in the study, no further treatment was warranted. The implications for quality-of-life are enormous!
In an editorial accompanying the main research paper, Dr. Hanna K. Sanoff of the University of North Carolina¡¯s Lineberger Comprehensive Cancer Center, observed that we still need to determine whether the observed ¡°clinical remission¡± after one year equates to a ¡°permanent cure.¡± That requires tracking the patients for at least five years total.
Furthermore, Dr. Kimmie Ng, a colorectal cancer expert at Harvard Medical School, says that while the results were ¡°remarkable¡± and ¡°unprecedented,¡± they would need to be replicated. And that¡¯s exactly what Dr. Diaz and his team at Memorial Sloan Kettering Cancer Center are in the process of doing.
More importantly, the team now plans to investigate whether dostarlimab can tackle other cancers in the same way. They are currently enrolling patients with stomach, prostate, and pancreatic cancers. If similar results can be replicated for these cancers, this would be a watershed moment for GlaxoSmithKline and a gamechanger for cancer treatment.
Such breakthroughs portend a coming era of enormous cancer-related opportunities. Patients, investors and researchers will all benefit.
Given this trend, we offer the following forecasts for your consideration.
First, as dostarlimab becomes widely used, it¡¯s price will come down making it more cost-effective.
Even at $100,000, dostarlimab would be cost-effective in treating a disease whose treatment now costs $167,000. However, the fact that GlaxoSmithKline has already discounted the price they charge the UK¡¯s National Health Service to roughly $61,000, indicates that the U. S. price could soon fall into that range.
Second, checkpoint inhibitors will become blockbuster drugs in the 2020s.
U.S. revenue from colorectal cancer treatment alone could be $10 billion a year. U.S. revenue related to prostate cancer could theoretically be another $10 billion. And global revenues could be several times that total.
Third, checkpoint inhibitors and other immunotherapies will dramatically improve the survival rate for cancer patients with far reaching benefits for healthcare costs, economic growth and quality-of-life.
Reducing the threat posed by life threatening cancer will deliver benefits similar to eliminating smallpox and polio. More people will have more productive years to devote to jobs and families. Healthcare dollars now spent on expensive surgery and radiation treatments will be reallocated to other applications. Happiness will also increase as people have one less thing to fear. And,
Fourth, as with many technological gamechangers, checkpoint inhibitors will be just one boulder in a ¡°technological avalanche.¡±
If replicated, this discovery represents a huge biomolecular breakthrough, which promises to change our lives for the better. But it certainly won¡¯t be the last! As we learn more about the body¡¯s complex cellular machinery, we¡¯ll be able harness other mechanisms to eliminate maladies that have plagued mankind for eons. And eventually, we¡¯ll look back from 2100 and wonder how we ever lived without these ¡°medical miracles.¡±
Resource List :
1. New England Journal of Medicine. June 23, 2022. Andrea Cercek, M.D., Melissa Lumish, M.D., Jenna Sinopoli, N.P., Jill Weiss, B.A., Jinru Shia, M.D., Michelle Lamendola-Essel, D.H.Sc., Imane H. El Dika, M.D., Neil Segal, M.D., Marina Shcherba, M.D., Ryan Sugarman, M.D., Ph.D., Zsofia Stadler, M.D., Rona Yaeger, M.D., J. Joshua Smith, M.D., Ph.D., Benoit Rousseau, M.D., Ph.D., Guillem Argiles, M.D., Miteshkumar Patel, M.S., Avni Desai, M.D., Leonard B. Saltz, M.D., Maria Widmar, M.D., Krishna Iyer, M.D., Ph.D., Janie Zhang, M.D., Nicole Gianino, M.S., Christopher Crane, M.D., Paul B. Romesser, M.D., Emmanouil P. Pappou, M.D., Ph.D., Philip Paty, M.D., Julio Garcia-Aguilar, M.D., Mithat Gonen, Ph.D., Marc Gollub, M.D., Martin R. Weiser, M.D., Kurt A. Schalper, M.D., Ph.D., and Luis A. Diaz, Jr., M.D. PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer.