Publications Update # 91
Non-Medical Article of the Week
Why Walmart’s warning may have more to do with weight-loss drugs than tariffs
Walmart's earnings were lower than expected this week. I found it very surprising when I read this article suggesting that GLP-1 blockers might be the culprit. The idea that Walmart's profits were tied to feeding people excessive food (perhaps junk food) - and now the loss of earnings linked to GLP-1 drugs — felt oddly satisfying. 🤪
HER2 Testing in Gyn Cancers
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Featured Paper Accompanying the Video - SPECTRUM STUDY
HER2 expression in a molecularly defined cohort of endometrial cancer patients: The SPECTRUM study - PubMed
This study highlights the distribution of HER2-low across EC molecular subtypes, with endometrial criteria proving more sensitive for identifying HER2-low cases, though HER2 status had no prognostic value in this cohort.
Alfonso Cortés-Salgado
HER2 Staining Criteria
| Criteria | Score 0 | Score 1+ | Score 2+ | Score 3+ |
|---|---|---|---|---|
| Endometrial | No staining observed | Incomplete membrane staining that is faint/barely perceptible in any proportion of cells or weak complete staining in <10% of tumor cells | Intense complete or basolateral/lateral membrane staining in ≤30% of tumor cells or weak to moderate staining in ≥10% of tumor cells | Intense complete or basolateral/lateral membrane staining in >30% of tumor cells |
| Breast | No staining or faint incomplete staining ≤10% of tumor cells | Incomplete membrane staining that is faint/barely perceptible and within >10% of tumor cells | Weak to moderate complete membrane staining in >10% of tumor cells or complete membrane staining that is intense but within ≤10% of tumor cells | Complete membrane staining that is intense and >10% of tumor cells |
| Gastric | No reactivity or membranous reactivity in <10% of cancer cells | Faint or barely perceptible membranous reactivity in ≥10% of tumor cells; cells are reactive only in part of their membrane | Weak to moderate complete, basolateral or lateral membranous reactivity in ≥10% of tumor cells | Strong complete, basolateral or lateral membranous reactivity in ≥10% of cancer cells |
IMPORTANT REFERENCE PAPERS
- DESTINY-PanTumor02 Phase II trial
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 pretreated patients with HER2-expressing tumors receiving T-DXd. Greatest benefit was observed for the IHC 3+ population. These data support the potential ro …
Funda Meric-Bernstam
- Fader et al.- Phase II trial
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 pretreated patients with HER2-expressing tumors receiving T-DXd. Greatest benefit was observed for the IHC 3+ population. These data support the potential ro …
Funda Meric-Bernstam- GY-026 trial
Testing the Addition of Trastuzumab or Trastuzumab/Pertuzumab to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma - Full Text View - ClinicalTrials.gov
Testing the Addition of Trastuzumab or Trastuzumab/Pertuzumab to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma - Full Text View.
- Gynecologic Pathology Paper by Dr. Buza
HER2 Testing and Reporting in Endometrial Serous Carcinoma: Practical Recommendations for HER2 Immunohistochemistry and Fluorescent In Situ Hybridization: Proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual Meeting - PubMed
Anti-HER2 therapy has recently emerged as an effective targeted treatment approach for patients with advanced stage and recurrent endometrial serous carcinoma, resulting in significantly prolonged progression-free and overall survival when combined with the standard chemotherapy regimen. Consequentl …
Natalia Buza- Breast CANCER study
Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer - PubMed
In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician’s choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, N …
Shanu Modi
Clear Cell Carcinoma
Pembrolizumab in Patients With Advanced Clear Cell Gynecological Cancer: A Phase 2 Nonrandomized Clinical Trial - PubMed
ClinicalTrials.gov Identifier: NCT03425565.
Rebecca Kristeleit
Year of Publication:
- 2025
Hypothesis:
- Pembrolizumab monotherapy provides clinical benefit in patients with previously treated advanced clear cell gynecological cancers (CCGC).
Inclusion Criteria:
- Histologically confirmed advanced CCGC
- PD-1 inhibitor–naive patients
- Prior chemotherapy (≥1 course)
- ECOG performance status 0-1
- Radiological progression of disease
Exclusion Criteria:
- Prior anti–PD-1/PD-L1 therapy
- Active autoimmune disease
- Central nervous system metastases
- Grade 2+ hypercalcemia
- Recent hospitalization for bowel obstruction
Primary End Point:
- 12-week progression-free survival (PFS) rate
Experimental Arm:
- Pembrolizumab 200 mg IV every 21 days (up to 2 years or until progression, discontinuation due to toxicity, or patient decision)
- Retreatment allowed for stable disease, partial response, or complete response at 2 years
Control Arm (or Standard Therapy):
- None (Single-arm trial)
Results:
| Outcome | Experimental (Pembrolizumab) |
|---|---|
| 12-week PFS rate | 42% (95% CI, 28-57) |
| Objective response rate (ORR) | 25% (95% CI, 14-40) |
| Median PFS | 2.7 months (95% CI, 1.3-5.4) |
| Median OS | 14.8 months (95% CI, 6.7-28.2) |
| Grade ≥3 TRAEs | 9 (19%) |
| Grade 4 or 5 TRAEs | 0 |
Conclusions:
- Pembrolizumab demonstrated clinical benefit in heavily pretreated advanced CCGC with a tolerable safety profile. Further evaluation in a randomized trial is warranted.
Limitations:
- Single-arm, non-randomized design
- Moderate sample size (48 patients)
- Lack of direct comparison to chemotherapy
- Biomarker analysis was exploratory and limited by small subgroups
GOOD REVIEW PAPER
Neuroendocrine cervical carcinomas: genomic insights, controversies in treatment strategies, and future directions: a NeCTuR study - PubMed
Neuroendocrine cervical carcinomas are rare, aggressive tumors with a high risk of early metastasis and poor survival outcomes. Despite existing therapies, over half of patients experience recurrence or progression after primary treatment, and survival after recurrence remains limited. Survival rate …
Gloria Salvo
For those of you studying for the board exams, this is a great review paper to download and read.
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