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Peter Attia MD#121 – Azra Raza, M.D.: Why we’re losing the war on cancer
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CHAPTERS
- 0:11 – 9:56
Intro and Why Azra Raza Wrote The First Cell
Peter Attia introduces Dr. Azra Raza and her book, then asks why a self-described non-writer wrote it. Raza explains that friends urged her, she has seen oncology as clinician, lab researcher and cancer widow, and that the death of her daughter's friend Andrew from glioblastoma drove her to write.
- •Attia describes the book as a critical look at the models used in cancer research and the poor return on spending
- •Raza brings three perspectives: oncologist, basic researcher with a lab, and cancer widow
- •A literary agent friend and his wife pushed her to write the book
- •Andrew, 22, was diagnosed with a nine-centimeter glioblastoma and the oncologists could do nothing
- •Attia frames the book's theme as poor return on investment despite money and effort
- 9:56 – 19:27
Why Raza Chose Oncology
Raza describes her childhood fascination with nature and her path into medicine in Pakistan. A first patient in medical school and the advanced tumors she saw in Karachi drew her to oncology. Attia shares memories of his own first oncology patients.
- •She was drawn to science from age four and medicine was the only route to science in Pakistan
- •Her first patient, a young woman with acute myeloid leukemia, set her thinking about liquid tumors as easier to study
- •Advanced tumors in Karachi gave her both an emotional and an intellectual hook
- •Attia and Steve Rosenberg's story show how early patients shape physicians
- •She teaches first-year students at Columbia and quotes Emily Dickinson on telling truth slant
- 19:27 – 35:00
Oncology Then and Now: Same Mortality as 1930 and Slash, Poison, Burn
Raza describes how cancer was seen when she began and argues that age-adjusted mortality today equals that of 1930, with the recent decline tracking reduced smoking. She traces the history of treatment from surgery in 500 BC to wartime chemicals and radiation, and says 68% of cancers are cured by those same tools.
- •Age-adjusted cancer mortality in 2020 is the same as in 1930, according to Raza
- •The recent decline in mortality parallels the decline in smoking
- •Breast surgery, chemical-weapon-derived drugs and radiation are essentially the same approaches used for generations
- •68% of new cases are cured by surgery, chemotherapy and radiation, while advanced disease is not
- •Attia and Raza agree that disease burden matters and that metastatic disease remains largely untreatable
- 35:00 – 39:45
Oncology's Celebrated Successes and Their Limits
Attia asks how much Gleevec and other successes have dented cancer mortality. Raza argues that CML, APL, lymphomas and melanoma are rare successes that together account for under 10% of cancers, and that they reinforced a paradigm of combining drugs that has held the field back.
- •Gleevec works in CML because it is caught in an early, chronic phase and is a rare disease
- •APL was cured with retinoic acid after Chinese clinicians showed it worked, with the mechanism found later
- •Hodgkin's success led to a paradigm of finding the right drug cocktail for other cancers
- •All of these successes together cover less than 10% of cancers
- •Attia raises checkpoint inhibitors as the optimistic counterargument
- 39:45 – 47:37
Immunotherapy, CAR T and Progression-Free Survival
Raza asks whether the quarter of a trillion dollars invested is reflected in a few checkpoint inhibitors, and criticizes CAR T cells for being unable to distinguish normal from cancer cells. She then says 95% of experimental cancer agents fail and that progression-free survival has replaced overall survival as the measure.
- •Raza questions whether progress reflects about a quarter of a trillion dollars spent
- •CAR T works for B cell cancers because B cell function can be replaced, but not for organs like the pancreas
- •Attia notes case studies of unique antigens and the autoimmune toxicities of checkpoint inhibitors
- •95% of experimental agents fail and the 5% that succeed extend survival by months for a minority
- •Progression-free survival has taken the place of overall survival
- 47:37 – 1:03:01
The Economics of New Cancer Drugs
Attia uses Avastin and the QALY concept to raise the cost of small survival gains. Raza gives the example of a liposomal seven-and-three AML regimen costing $45,000 versus $5,000 for a median 3.7-month gain, and links this to FDA standards, legal pressure, and patient financial ruin.
- •Attia explains Avastin's roughly four-month median gain and the QALY debate
- •Seven-and-three has been the AML backbone since 1977, with better supportive care raising five-year survival from 10% to about 26%
- •The $45,000 version is approved on a 3.7-month median survival improvement
- •Raza says oncologists fear lawsuits if they don't prescribe, and the FDA has lowered its bar under advocacy pressure
- •42% of patients are financially ruined by year two, and Attia calls the US a subsidizer of drug development
- 1:03:01 – 1:10:51
Good Intentions, Monetization and the Role of Pharma
Raza recounts her widowhood and the Ballad of Reading Gaol to explain how good beginnings turn self-destructive, then criticizes monetizing ideas before early trials. Attia lays out how funding is split between NCI and pharma and asks whether shareholder incentives can ever put patients first.
- •Raza uses Oscar Wilde's refrain to describe a field that changes the evidence rather than its concept
- •She objects to companies being formed before phase one trials
- •Attia describes NCI's large share of funding and pharma's outsourcing of early R&D to biotech
- •Attia questions whether shareholder-driven companies can prioritize patients and notes the cost to everyone else's resources
- •Raza uses the boiling frog analogy for a system that slowly became broken
- 1:10:51 – 1:19:13
Why 95% of Cancer Drugs Fail: Flawed Preclinical Models
Raza argues that cell lines and mouse models are artificial, with cell lines drifting transcriptionally away from their tissue of origin. Attia clarifies the point that killing cancer is easy but killing it selectively is hard, and Raza adds that up to 90% of high-profile papers are irreproducible.
- •Cell lines such as HeLa are immortalized and express similar genes irrespective of tissue origin
- •Findings in these models may not be relevant to human cancer
- •Attia notes killing cancer cells is easy, but doing so without harming the patient is the challenge
- •Raza says up to 90% of papers in top journals are irreproducible
- •NCI and philanthropic funding of roughly $12 billion a year still support the same platforms
- 1:19:13 – 1:22:37
The Academic–Industry Pipeline and Misaligned Incentives
Raza describes how academic grants fund only limited work while taking a drug to market costs billions, making academia and industry dependent on each other. Attia adds that publishing incentives are similarly skewed and says he is discouraged about the path from bench to bedside.
- •Academic grants of a few hundred thousand dollars support study of a single gene or pathway
- •A phase I trial costs about $30 million and approval about $2.5 billion, which only industry can fund
- •Young faculty are asked mainly how many clinical trials they will open
- •Attia says publication incentives produced a cottage industry of low-quality papers
- •Attia says he is discouraged about the bench-to-bedside process
- 1:22:37 – 1:40:04
Raza's Solution: Early Detection and Human-Based Research
Raza says early detection is the only thing that has worked and calls for continuous monitoring with biomarker chips, genomics and AI. She argues for drug development in human tissue rather than animals, and Attia agrees, adding a prevention, screening and early-treatment framework and describing liquid biopsy efforts.
- •Raza cites Peter De Vries's 1961 line comparing leukemia treatment to a local train, with the same run and a few more stops
- •She opposes using animals for drug development and efficacy and notes the FDA's phase zero approach
- •She describes the FDA-approved M-chip for PSA and a company claiming detection of 13 cancers from a drop of blood
- •Attia's three rules: avoid cancer, screen smartly, treat when cells number millions rather than billions
- •Raza says cancer risk is largely random mutation accumulating with age, like grains of sand in a pile, and wants 50% of spending on prevention and early detection
- 1:40:04 – 1:46:06
Omar's Story and the Need for a New Paradigm
Attia asks why Raza included Omar in her book, and she describes a young man's osteogenic sarcoma and the helplessness of oncologists. She then criticizes nonprofit hospitals and higher education alike and says that, following Kuhn, a better paradigm of early detection must be shown.
- •Omar was the son of her best friend, diagnosed at 38, with a tumor that could not be fully resected
- •Raza chose patients of different ages and cancer types for the book
- •Nonprofit hospitals earn large profits and spend them on administrators and acquisitions
- •Raza says patients and doctors have the skin in the game while businessmen run the show
- •She predicts a shift from 2020 to 2030 toward early detection and prevention, and Attia is optimistic about liquid biopsies
- 1:46:06 – 1:54:54
Coping with Loss and an Optimistic Close
Attia asks how Raza coped with her husband Harvey's death from cancer. She describes anger and grief, Harvey's own acceptance, and a Dickinson poem, then closes by describing her large tissue repository and her optimism that it can help find the first cell.
- •Raza went through every emotion, including anger and crying fits, while Harvey reached acceptance
- •Harvey said he was glad the diagnosis was his rather than his wife's or daughter's
- •She quotes Dickinson on having no time to hate or love beyond a little toil of love
- •Her repository since 1984 holds over sixty thousand samples from patients followed over time, all collected by her
- •She says she is very optimistic about the future of cancer research
