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Azra Raza, M.D.: Why We’re Losing the War on Cancer | The Drive with Peter Attia #121

Key Takeaways

  • “Do the advances really reflect the quarter of a trillion dollars we’ve invested in research?” – Dr. Azra Raza
  • We have spent a lot of money and made limited progress but by any objective metric the return on investment in cancer research has been paltry – it’s time to try something else  
  • We have falsely become convinced of a paradigm that we just have to find the right cocktail of drugs for each type of cancer  
  • Medicine has perfected the art of prolonging disease
  • “We are living in an era of the most sophisticated technological advances possible, and yet the treatment of cancer is paleolithic.” – Dr. Azra Raza
  • We need to refocus our energy into what has worked: Early detection
  • “Mark my words, the coming decade of 2020-2030 will see this shift from treating disease to trying to detect early and prevent the disease from becoming established.” – Dr. Azra Raza

Introduction

Dr. Azra Raza (@AzraRazaMD) is the Chan Soon-Shiong Professor of Medicine and Director of the MDS Center at Columbia University in New York and an outspoken advocate for reconfiguring the way we treat cancer.

Dr. Azra Raza has experienced cancer from three paradigms: as a practicing oncologist, a researcher, and a cancer widow. Her experiences led her to author the book, The First Cell: And the Human Costs of Pursuing Cancer to the Last.

Host: Peter Attia (@PeterAttiaMD)

Cancer: Then & Now  

  • We have found evidence of cancer in mummies, so we know it has been around a long time in human history
  • Previously, it was almost a stigma to have cancer because it was associated with genetic or environmental toxins and adverse behaviors like smoking
  • Stigma led to people hiding tumors or presenting with advanced cancer by the time they showed up at the hospital
  • Today, we recognize the correlation between genetics, pathogens, and environmental exposure but there is no obvious reason we can identify for most people who get cancer
  • The vast majority of cancers are random mutations which means cancer is more common with age as the body becomes unstable because of errors in cell copying

The Basics of Cancer Treatment Really Haven’t Changed

  • The first treatment of cancer was in 500 BC when Persian queen felt a lump in her breast and eventually had a slave slash her breast off
  • In the early days, when there was a physical tumor, we would cut it out; when there was a liquid tumor, we would find a way to poison it and kill it
  • What have we changed? Today we use lumpectomy, mastectomy, chemotherapy, radiation
  • The first three chemical weapons used against cancer are still in use today – we’re still slashing, burning, and radiating the same way
  • Apart from targeted therapies and antibodies, we’re using the same methods  
  • Supportive care measures are better: we have better antivirals, quality of transfusions is better, etc. but the backbone of treatments hasn’t changed drastically
  • “We are living in an era of the most sophisticated technological advances possible, and yet the treatment of cancer is paleolithic.” – Dr. Azra Raza

Problems with Measurement of Cancer Outcomes

  • “The only good news you can give to a cancer patient is, ‘we caught it early, we can get rid of it’” – Dr. Azra Raza
  • Success of treatment in cancer is measured by age adjusted mortality (the death rate that controls for the effects of differences in population age distribution)
  • In 2020, the age adjusted mortality for cancer is the same as it was in 1930
  • People often point to a 27% decline we’re seeing in overall mortality but that is following a 30 year increase in mortality following the peak of smoking
  • All we’re seeing is the incidence decline in mortality from cancer paralleling the decline in smoking, we’re really at square one
  • We talk about progression-free survival now, not flat out survival
  •  “We don’t really have therapy that works for systemic disease – you are no better off today than you were 50 years ago. That’s a sobering and outright depressing statistic.” – Peter Attia

Impact of Higher Costs & Monetization of Cancer Drugs

  • We have falsely become convinced of a paradigm that we just have to find the right cocktail of drugs for each type of cancer
  • We’re monetizing trials and forming new companies before Phase 1 trials even start
  • Advocacy groups seeking to tout advancements are demanding more drugs for cancer patients at any cost
  • Our models fall short: “95% of drugs we bring to the bedside fail because pretesting platforms are so artificial.” – Dr. Azra Raza
  • Newer drugs that have been developed cost 9x as much as the originals and only have the potential to increase lifespan by a median of 3.7 months in otherwise healthy individuals
  • Only 30% of patients will experience these additional months of life
  • Physicians feel forced to prescribe these expensive treatments though efficacy is unlikely because of the potential of lawsuits by families who feel slighted
  • Decisions are no longer unilaterally made by oncologists, but rather heavily influenced by key opinion leaders and governmental institutions under pressure
  • “FDA has lowered its bar of approving drugs to laughable criteria. It would be laughable if it wasn’t so tragic.” – Dr. Azra Raza
  • 42% of cancer patients who are diagnosed today will be financially ruined by the second year of their diagnosis
  • Book: “The Price We Pay: What Broke American Health Care – And How To Fix It” by Marty Makary, MD
  • “Do the advances really reflect the quarter of a trillion dollars we’ve invested in research?” – Dr. Azra Raza

Big Pharma, Academia, and Clinical Trials are Failing Us

  • Pharmaceutical companies are the easiest target but are the symptom of a broader issue
  • Pharmaceutical companies have outsourced R&D which is switching to venture investors and private entities
  • Research progress is largely funded by private or governmental agencies such as NIH
  • More than half of total research dollars in the world in oncology are funneled through the National Cancer Institute (NCI)  
  • The systems of research and development in America are broken
  • Academics develop the biologic insight needed to develop targets but don’t have the bandwidth to take it to the patient
  • Clinical trial patients represent the upper limit of what we see in the real world – patients are the best of the best with fully functioning and healthy organs and metabolic systems
  • “Up to 90% of papers published in the highest-profile journals of science are irreproducible” – Dr. Azra Raza
  • “I have brought patients back front and center. Everything I look at is through patient, human anguish. Our problem is 90% of researchers never see a cancer patient because they are scientists and study tumors they grow on their own in labs. They don’t see a disease they are trying to develop treatment for.” – Dr. Azra Raza

Immune Therapy Advances in Cancer

  • The two treatments that are most celebrated are treatments of chronic myeloid leukemia and acute promyelocytic leukemia
  • For both diseases, we have a magic bullet but still only effective when caught early
  • We have seen a dramatic difference in survival of melanoma and myelomas but this only accounts for about 10% of cancers
  • Two main advances in immune therapy: cell therapies and checkpoint inhibitors
  • Cell therapies: take the body’s immune cells and engineer in a way to selectively kill cancer
  • Checkpoint inhibitors: target checkpoints so the body’s immune cells recognize cancer as being alien to the normal function of body and must be eliminated
  • “CAR-T cells have been proclaimed as revolutionary and the science is beautiful, but it has actually done very little for patients because CAR-T cells can’t distinguish between healthy and cancerous cells – they kill indiscriminately as well.” – Dr. Azra Raza
  • “There are whole industries sprouting up to deal with the symptoms of CAR-T cell therapy.” – Dr. Azra Raza

How Can We Course Correct Cancer Treatment?

  • We’ve spent a lot of money and made limited progress but by any objective metric the return on investment in cancer research has been paltry – it’s time to try something else  
  • What you learn in drug development testing on animals is only correct for animals – it does not automatically extrapolate to humans
  • We need to study human tissue
  •  “We began with good intentions but have immortalized invitro cultures that are so skewed they no longer represent humans” – Dr. Azra Raza
  • Early detection has worked – we need to stop trying to reinvest the drug discovery wheel, coming up with new cocktails and instead refocus our energy
  • “Instead of spending 5% into early detection and prevention, let’s spend 50%” – Dr. Azra Raza
  • We should take advantage of cutting edge genomics, scanning and imaging devices, artificial intelligence, etc to identify biomarkers and monitor the human body continuously
  • For each cancer we should develop the earliest monitoring and detection which can be done with just a drop of blood and provide results within hours
  • “Mark my words, the coming decade of 2020-2030 will see this shift from treating disease to trying to detect early and prevent the disease from becoming established.” – Dr. Azra Raza
  • For more information, see companies such as GRAIL
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