Table of Contents:

Episode 4.01: IMpower- 010 [16:12]

• Study to Assess Safety and Efficacy of Atezolizumab (MPDL3280A) Compared to Best Supportive Care Following Chemotherapy in Patients With Lung Cancer [IMpower010]

  <aside> ⚕️ "This is a Phase III, global, multicenter, open-label, randomized study to compare the efficacy and safety of 16 cycles (1 cycle duration=21 days) of atezolizumab (MPDL3280A) treatment compared with best supportive care (BSC) in participants with Stage IB-Stage IIIA non-small cell lung cancer (NSCLC) following resection and adjuvant chemotherapy, as measured by disease-free survival (DFS) as assessed by the investigator and overall survival (OS). Participants, after completing up to 4 cycles of adjuvant cisplatin-based chemotherapy, will be randomized in a 1:1 ratio to receive atezolizumab for 16 cycles or BSC." - Source

  </aside>

  

  Source

• What is the real goal of adjuvant therapy?

  1. To increase the curative fraction
  2. Increase overall survival
  3. To increase quality of life

• Population

  • Patients all had to have gotten between one and four cycles of chemotherapy
    • This bothered VP, because he believes all people should have received four cycles of chemotherapy
      • By allowing the protocol to enroll people who just got one cycle of chemotherapy, you might inadvertently encourage people not to get proper adjuvant chemotherapy

• Question 1

  • Are they patients getting proper staging?
  • What does inadequate staging do?
    • If you don't do staging properly, there will be occult metastatic disease in the study

• Question 2

  • When patients progress, do they receive chemotherapy + IO?
    • Which leads to the next question
      • Is there a survival benefit to giving chemo + IO upfront versus giving it on the backend?
        • Cytotoxics + IO (not cytotoxics alone) has the ability to purge the body of metastatic disease

• DFS

  

  Source

  

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  • It will be important to see the adjacent subgroups for DFS

Episode 4.01: KEYNOTE-564 [30:00]

• Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (MK-3475-564/KEYNOTE-564)

  <aside> ⚕️ *"The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in the adjuvant treatment of adult participants who have undergone nephrectomy and have intermediate-high risk, high risk, or M1 no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component.

  The primary study hypothesis is that pembrolizumab is superior to placebo with respect to Disease-free Survival (DFS) as assessed by the Investigator in male and female participants with intermediate-high risk, high risk and M1 NED RCC." - Source*

  </aside>

Source

• Methods

  • Key inclusion criteria include age ≥18 years
    • histologically confirmed clear cell RCC of:
      1. Intermediate-high risk (pT2, grade 4 or sarcomatoid, N0 M0; or pT3, any grade, N0 M0)
      2. High risk (pT4, any grade, N0 M0; or pT any stage, any grade, N+ M0)
      3. M1 NED; no prior systemic therapy for advanced RCC

• DFS

  

  Source

  • DFS has a statistically significant benefit, but the curves come back together
    • Will this be the case when the data matures?
      • Is the therapy simply delaying DFS?

• Forest plot

  

  Source

  • M1 NED is doing the heavy lifting because metastatic patients who just had something excised are receiving treatment
    • Does this fall underneath the adjuvant umbrella?
      • We will want to see the effect on the real M0 patients

Episode 4.01: OlympiA [33:00]

• Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer

  <aside> ⚕️ "We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease–free survival."- Tutt et al.

  </aside>

• Issues

  <aside> ⚕️ "Those who were treated with neoadjuvant chemotherapy were required to have not had a pathological complete response with a CPS+EG score of 3 or higher. The CPS+EG scoring system estimates relapse probability on the basis of clinical and pathological stage (CPS) and estrogen-receptor status and histologic grade (EG); scores range from 0 to 6, with higher scores indicating worse prognosis" - Tutt et al.

  </aside>

  • This is an issue because the results of Xeloda were presented in 2015 at San Antonio

    "If you know before your trial runs that your control arm is a negligent standard of care. Or if you know, early on in a study, or if you know later on–you have got to upend the control arm." - Dr. Prasad

• Endpoints

  

  Source