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#133 - Vinay Prasad, M.D., M.P.H: Hallmarks of successful cancer policy — Whalespan

Content›Video›#133 - Vinay Prasad, M.D., M…

#133 - Vinay Prasad, M.D., M.P.H: Hallmarks of successful cancer policy

Peter Attia2h 12m · 2020-10-19

Claims Made

239

Claims Supported

117

Support Rate

49%

Support rate

117 of 239 claims supported

117 supported122 partial / not

Claims from this content

91

✓Well SupportedMetabolic diseases like fatty liver disease and type 2 diabetes increase the risk of cardiovascular disease, cancer, and dementia by 25-50%.✓Well SupportedCardiovascular disease is the most preventable of the major disease categories (atherosclerosis, cancer, neurodegenerative disease) due to better understanding of its pathology and more effective prevention tools.✓Well SupportedPatients with Lynch syndrome have a high number of mutations, making them candidates for checkpoint inhibitor trials.✕Not SupportedThe addition of a few months of survival for metastatic cancer patients represents a minimal and potentially insignificant improvement.

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Attia walks back the clinic protocol: too aggressive for healthy adults

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A. Volkovreader

4h

Bookmarking — the dossier-vs-overview split is the right call. Most of the time I want overview; sometimes I want receipts.

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✕Not Supported

Some cancer drugs may have a net downside, not improving survival and incurring opportunity costs.

◐Partially SupportedAvastin provided a survival benefit of about two months in its initial colon cancer indication.

◐Partially SupportedApproved liquid biopsy tests can identify mutations for which drugs exist, offering a less invasive alternative to tissue biopsy.

✕Not SupportedThe 30% tumor shrinkage cutoff for approving cancer drugs is an arbitrary measure not directly indicating efficacy.

◐Partially SupportedOpening a blocked artery in STEMI patients saves lives.

◐Partially SupportedCheckpoint inhibitors like Keytruda are highly effective when they work and ineffective when they do not.

✓Well SupportedHormone replacement therapy in postmenopausal women was found by the Women's Health Initiative trial to increase thromboembolic and cardiovascular events.

✓Well SupportedCancer is a broad category encompassing many distinct diseases.

◐Partially SupportedIn pancreas cancer patients with a germline BRCA mutation, olaparib provided a progression-free survival benefit but did not improve overall survival compared to placebo.

◐Partially SupportedThe survival benefit of sorafenib for unresectable liver cancer is approximately 3 months.

◐Partially SupportedBRAF mutations should be tested for in melanoma.

◐Partially SupportedCAR-T cell therapies costing $300,000-$400,000 are rationalized as one-time doses compared to annual drugs.

◐Partially SupportedWhen interpreting genetic test results for cancer, be cautious not to solely pursue findings that might lead away from treatments with better track records.

◐Partially SupportedTwo-thirds of cancer drugs are approved based on metrics like tumor shrinkage or delayed tumor growth, rather than survival or quality of life.

◐Partially SupportedA p-value cutoff of 0.05 in clinical trials may lead to positive results by chance alone.

◐Partially SupportedAvastin offers only a 1-2 month median survival benefit and does not cure patients.

◐Partially SupportedStents were widely used for chronic stable angina despite the Courage trial finding they did not lower heart attack rates or improve longevity.

◐Partially SupportedPatients often believe stenting improves survival or longevity, even when evidence suggests otherwise for chronic stable angina.

◐Partially SupportedProgression-free survival in cancer trials is the time from enrollment until death, new lesion development, a 20% increase in tumor size, or a 20% tumor shrinkage before growth.

◐Partially SupportedTumors can have different mutations in different metastatic sites, making precise therapy challenging.

◐Partially SupportedPolicy related to cancer treatment and regulation can be distilled into six essential hallmarks.

✕Not SupportedFor patients with chronic stable angina, stenting does not improve survival or reduce the rate of subsequent heart attacks.

✕Not SupportedStents can be overused in less severe situations, such as for individuals with minor arterial narrowing and mild angina.

?Limited ResearchOmitting Avastin from colon cancer treatment may result in only a very slight difference in outcomes compared to standard treatment.

◐Partially SupportedSham arthroscopic knee surgery yields no difference in outcomes compared to actual debridement surgery.

✕Not SupportedHealthcare interventions like consistent use of blood pressure medications have a higher return on investment than Avastin.

✕Not SupportedA drug that lowers a blood protein, causing ocular impairment and blindness in many users, was approved despite questionable data and significant healthcare costs.

✕Not SupportedClinical trial designs can be manipulated by curating patient populations and testing new drugs against less effective older drugs.

✕Not SupportedMany purported 'game-changer' cancer treatments lack substantive benefits upon critical examination.

◐Partially SupportedTargeted therapy inhibiting the BCR-ABL fusion can restore near-normal life expectancy for chronic myeloid leukemia (CML).

◐Partially SupportedVinay Prasad believes liquid biopsies warrant further study through rigorous clinical trials.

◐Partially SupportedSurgical procedures like the Whipple procedure and radical mastectomies have significantly lower mortality and morbidity rates today compared to 50 years ago.

◐Partially SupportedTrastuzumab, a breast cancer drug, was accessed by only 1% of eligible patients in India five years ago.

◐Partially SupportedRadiotherapy can offer a long-lasting cure for localized cancers.

◐Partially SupportedThe benefits of cancer drugs observed in clinical trials may not translate to the general population and can evaporate in real-world application.

◐Partially SupportedThe Women's Health Initiative study's finding of increased breast cancer risk has been abandoned.

◐Partially SupportedThe serial nature of liquid biopsies, allowing for tracking of disease over time, may be their most significant benefit.

◐Partially SupportedAccepting the risk of a medical procedure is only justifiable if the procedure offers a net benefit.

◐Partially SupportedHodgkin's lymphoma and widespread testicular cancer are curable with current drug combinations.

◐Partially SupportedNon-small cell lung cancer has numerous molecular categories, including EGFR mutation-driven and RAS-driven subtypes.

◐Partially SupportedMicrosatellite instability-high (MSI-high) status is a reasonable test for pancreatic cancer, regardless of tumor type, and has an approved drug.

◐Partially SupportedEGFR and ALK mutations are important to test for in lung cancer, particularly in younger, non-smoking individuals.

◐Partially SupportedLung cancer patients should be tested for at least six or seven mutations for which FDA-approved therapies exist.

◐Partially SupportedNext-generation sequencing can match patients with clinical trials.

◐Partially SupportedMSI-high status should be tested for in colon cancer.

◐Partially SupportedCell-based therapies like CAR-T show promise but their benefit across all conditions, such as in multiple myeloma, is still under investigation.

◐Partially SupportedDexamethasone showed a mortality benefit for hospitalized COVID-19 patients requiring oxygen or mechanical ventilation, but may have harmed or provided no benefit to hospitalized patients not requiring supplemental oxygen.

◐Partially SupportedGleevec provides a significant benefit for the cancers it treats.

◐Partially SupportedThe high cost of olaparib and the perception of new targeted drugs versus older chemotherapy can create a disconnect regarding treatment benefits.

◐Partially SupportedThe sensitivity of liquid biopsy tests and the need for tumor tissue biopsy vary by test and mutation.

◐Partially SupportedSurvival rates for heart attack are significantly better in 2020 compared to 1960 due to advancements in cardiac life support, cholesterol-lowering drugs, blood pressure management, and stent technology.

◐Partially SupportedLeukemia is often studied early in liquid biopsy development because it is readily accessible for volume tracking.

◐Partially SupportedSequencing different tumor sites within the same body can reveal different mutations, potentially leading to different drug choices for each site.

◐Partially SupportedA stent is a small, expandable metallic tube placed in a coronary artery to address blockages.

◐Partially SupportedSmart, well-intentioned people with plausible pathophysiology and compelling retrospective observational data can be wrong about medical interventions.

◐Partially SupportedFor localized cancer, surgical removal is generally a 'no regret' move.

◐Partially SupportedThe 'Hallmarks of Cancer' paper by Hanahan and Weinberg is highly influential and widely cited in oncology.

◐Partially SupportedMechanical interventions performed to alleviate subjective symptoms like angina, pain, dyspnea, or back pain are often no better than sham interventions.

◐Partially SupportedSham interventions are a useful method to differentiate the benefit derived from a specific medical procedure versus the benefit from patient reassurance and the placebo effect.

◐Partially SupportedTumor sample sequencing results can vary between different companies, raising concerns for precision therapy.

◐Partially SupportedDrugs that suppress premature ventricular contractions after a heart attack increased the risk of dying in the CAST trial.

◐Partially SupportedThe ORBITA study demonstrated that stenting for stable angina provided no significant improvement in exercise tolerance compared to a sham procedure.

◐Partially SupportedPharmaceutical companies tend to increase drug prices in lockstep, gradually over time, to avoid significant public backlash.

◐Partially SupportedThe UK's better life expectancy and lower healthcare spending suggest a potentially more effective overall healthcare system despite potentially worse cancer outcomes compared to the US.

◐Partially SupportedA new cancer drug that extended median survival from six months to eleven months was celebrated with standing ovations at a national oncology conference.

◐Partially SupportedNew cancer drugs reaching the market provide an average of a 2.1-month improvement in survival.

◐Partially SupportedNew cancer drugs can cost $100,000 to $200,000 per year, with patients potentially spending nearly $100,000 for a two-month survival benefit.

◐Partially SupportedMedical reversal describes interventions based on weak or contradictory evidence.

✕Not SupportedA drug that only improves progression-free survival without increasing lifespan or well-being may be problematic.

✕Not SupportedClass 1c antiarrhythmic drugs were abandoned due to studies showing they increased the risk of dying.

◐Partially SupportedA published protocol and statistical analysis plan can provide sufficient evidence to act on drug trial results before full paper release, especially during a pandemic.

◐Partially SupportedPembrolizumab (Keytruda) can lead to long-term remission in patients with Lynch syndrome and checkpoint mutations.

◐Partially SupportedClinical trial populations are often younger, healthier, and have fewer comorbidities than the average cancer patient, potentially inflating the perceived benefit of new drugs.

◐Partially SupportedPatients with rare tumor types or younger ages should look for fusion events in addition to common mutations with approved drugs.

◐Partially SupportedAverage clinic patients are less healthy than clinical trial participants, leading to reduced drug tolerance.

◐Partially SupportedVinay Prasad advocates for waiting for full published papers and more information before acting on trial results.

◐Partially SupportedCancer treatments with low toxicity or reversible toxicities, where benefits outweigh risks, are considered 'no-brainer' choices.

◐Partially SupportedPhysicians should help patients if toxicity is warranted and the patient desires it.

◐Partially SupportedMeasuring tumors on a CT scan is imprecise and can be subject to dispute regarding boundaries.

◐Partially SupportedCMS allows Medicare to pay for drugs for uses beyond their initial approval if expert doctors recommend them.

◐Partially SupportedCutting off a tumor's blood supply may stop its growth.

◐Partially SupportedAnti-VEGF compounds are a new class of cancer drugs targeting tumor blood supply.

◐Partially SupportedGleevec (imatinib) was approved around 2001 for gastrointestinal stromal tumors (GIST).

◐Partially SupportedPatient advocacy groups are often heavily funded by the pharmaceutical industry.

✕Not SupportedThe Women's Health Initiative (WHI) study is considered one of the worst studies ever conducted.

◐Partially SupportedThe perceived benefit from procedures like arthroscopic knee surgery, vertebral cement injections, shoulder procedures, and stenting for chronic stable angina is primarily due to the psychological stimulus of the intervention, not the intervention itself.

◐Partially SupportedThe Orbital trial showed stenting for chronic stable angina provided a statistically insignificant and clinically meaningless improvement in exercise duration compared to a sham procedure.