Table of Contents

Talazoparib [Episode 1.03–16:38]

• Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation

  • The hazard ratio for disease progression or death was 0.58

• This is a cookie cutter trial that is emblematic of poorly constructed studies

  • Very similar to the OympiAD study
    • The hazard ratio for disease progression or death was 0.58

• The statement that "competition lowers drug prices" may have some merit

  • But this is not true in the cancer drug space

• Primary endpoint

  • The primary endpoint, progression-free survival (PFS), is a surrogate endpoint
    • Overall survival was not improved

• Lethal condition

  • When these drugs cost a fortune, these trials and drugs should strive to make an improvement in overall survival
    • Especially in a lethal disease such as advanced breast cancer with a BRCA 1/2 mutation
  • Oncology seems to "accept" these results–clinicians need to raise their bar for approval of these drugs

• Bishal Gyawali's Commentary

  • PFS in first line metastatic breast cancer is a bad predictor for OS
    • Paper by Prasad and colleagues looked at the strength of association between surrogate end points and survival in oncology

  <aside> ⚕️ "However, whether the PFS benefit correlates with OS is a moot point here because the OS results (not surprisingly) are already available." - Gyawali ~ "Although olaparib seems to have won the Gold with OlympiAD, the patients probably have not. We need to stop celebrating a gold-plated bronze as a true gold so that one day our patients can finally get the gold they deserve." - Gyawali

  </aside>

• Lack of OS benefit

  • Dr. Prasad's response to critics on the lack of OS benefit was that only a small amount of patients on the control arm (~18%) got other PARP inhibitors

• Lack of Standard of Care

  • The control arm therapy was inadequate (capecitabine, eribulin, gemcitabine, or vinorelbine)
    • Platinum therapy was not an option

• Toxicity

  • The summary of adverse events showed that the talazoparib group had much worse toxicity than the STG
    • There were more hematologic side effects with the PARP inhibitor as well

• Exploratory end points

  • The study claimed that the experimental arm experienced an improvement in quality of life (QoL)
  • Exploratory end points tend to have selection bias
    • EORTC QLQ-C30 questionnaire

• Medical writers

  • "We thank ___ ___, and ___ ___, for medical writing and editorial assistance with an earlier version of the manuscript" - Litton et al.
    • Research scientists must write their own papers–enough with the medical writers

FDA Approval for Nivolumab in Small-cell Lung Cancer [Episode 1.03–30:30]

• CheckMate-032 Study
  • After 2 years 4 months and 24 days of having the data–approval occured based on a 12% RR
    • It seems as if this was a last ditch effort for an accelerated approval of a checkpoint inhibitor in this disease setting since the IMpower133 study was around the corner
• IMpower133 Study
  • Concluded that atezolizumab + chemotherapy in the first-line treatment of NSCLC resulted in sig. improvements in OS and PFS than chemotherapy alone
• Every approval in the future needs to specify MSI-high (MSI-H) v. MSI-low (MSI-L)
  • The paper by Luis Diaz et al. suggests that the RR are probably comparable