Subscribe

Publications Update # 34

Last updated on 
Publications Update # 34
Photo by Aaron Burden / Unsplash

Non-Medical Article of the Week

The World Is Going Blind. Taiwan Offers a Warning, and a Cure
So many people are nearsighted on the island nation that they have already glimpsed what could be coming for the rest of us.
WIREDCondé Nast
The Myopia Generation
Why do so many kids need glasses now?
The AtlanticSarah Zhang

The journey of scientific discovery often hinges on our willingness to adapt our understanding when faced with new evidence. A sudden rise in nearsightedness among kids, which nudged experts to challenge the old belief that bad eyesight was a genetic inheritance, exemplifies that. The curiosity and subsequent investigations highlighted how our modern lifestyle, dominated by screens and lacking in outdoor adventures might be ruining our eyesight. This whole scenario underscores the essence of staying open to changing narratives in science. So, as you read these articles, think about our daily understanding of the malignancies we manage. What can you challenge and create a new narrative?

Ovarian Cancer

DESTINY-PanTumor02

Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial - PubMed
Our study demonstrates durable clinical benefit, meaningful survival outcomes, and safety consistent with the known profile (including ILD) in pre-treated patients with HER2-expressing tumors receiving T-DXd. Greatest benefit was observed for the IHC 3+ population. These data support the potential r…
PubMedFunda Meric-Bernstam

Summary:

Phase II study evaluating the role of HER2-directed ADC Trastuzumab deruxtecan (T-DxD) in several cancers.

Enhertu is the trade name for this ADC.

  • deruxtecan - Topoisomerase I inhibitor
  • HER2 testing is done via IHC - 3+ and 2+ allowed
  • Prior HER2-directed therapy allowed
  • Primary endpoint - Objective response rate (ORR)
    • Uterus - in 2+ IHC -->47% (n=17); in 3+ IHC --> 84.6% (n=13)
    • Cervix - in 2+ IHC --> 40% (n=20); in 3+ IHC patients --> 75% (n=8)
    • Ovary - in 2+ IHC --> 36.9% (n=19); in 3+ IHC patients -->64% (n=11)
  • Toxicity
    • Risk of pulmonary adverse events - primarily interstitial lung disease (10%, 28 patients in the entire study), 1 grade 3 and three fatal events (1.1%) due to ILD
    • 35% of patients in endometrial, 47% in cervical, and 42% in ovarian cohorts with grade 3 or more toxicity. 2 deaths in endometrial (7.55%, 3/40).
    • 1/3 of patients in the gyn cohort were hospitalized during therapy due to complications
    • 50% need dose modifications needed
💡
Excellent response rates, but it's a phase 2 study. Confirmatory phase III trials will be needed. Toxicity management is going to be critical in making sure patients can handle this drug.

Endometrial Cancer

Isolated Vaginal Recurrences

Isolated vaginal recurrence in women with stage I endometrial cancer - PubMed
Isolated vaginal recurrences in stage I endometrial cancer are detected earlier than non-vaginal recurrences. Surgical approach does not appear to impact recurrence. Adjuvant VBT after primary surgery carries a 1%-2% risk of isolated vaginal apex recurrence.
PubMedEric Rios-Doria

An excellent study from the combined MD Anderson and MSKCC endometrial cancer database. Can someone calculate the number need to treat our surveillance visits for endometrial cancer vaginal recurrences?

Ovarian Cancer

Immunotherapy in Ovarian Cancer

Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100 - PubMed
ClinicalTrials.gov, NCT02674061.
PubMedJonathan A Ledermann
Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032) - PubMed
The study was terminated due to the observed ORR at the interim futility analysis. This highlights a need for effective therapies in treating patients with recurrent BRCAwt PROC.
PubMedLeslie M Randall

Two more trials in ovarian cancer showed no benefit of immunotherapy. Add these to the list of the two I sent out in Publications Update # 29

Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39) - PubMed
Current evidence does not support the use of immune checkpoint inhibitors in newly diagnosed OC. Insight from this trial should inform further evaluation of immunotherapy in OC.
PubMedKathleen N Moore
Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial - PubMed
ATALANTE/ENGOT-ov29 did not meet its coprimary PFS objectives in the ITT or PD-L1-positive populations. OS follow-up continues. Further research on biopsy samples is warranted to decipher the immunologic landscape of late-relapsing OC.
PubMedJean-Emmanuel Kurtz

However, there is one exception - a single phase II study of 40 patients that is driving the use of Cytoxan, Avastin, and Pembro in ovarian cancer. No comparative arm. Given the cost of this regimen, I think a confirmatory trial is desperately needed with a control arm getting cytoxan and Avastin alone.

Efficacy and Safety of Pembrolizumab in Combination With Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Ovarian Cancer: A Phase 2 Nonrandomized Clinical Trial - PubMed
ClinicalTrials.gov Identifier: NCT02853318.
PubMedEmese Zsiros
💡
Phase II studies should not change practice - especially when the cost of care is becoming a major crisis in the US. This combination should be studied in the Phase III trial with the appropriate control arm.

That's it for today