For many years, biomarker testing in ovarian cancer was not centered on immunotherapy selection.
Clinical decision-making relied primarily on:
- Histology and stage
- Platinum sensitivity vs resistance
- BRCA1/2 mutation and homologous recombination deficiency (HRD) status for PARP inhibitor use
Although PD-L1 expression could be measured in research settings, it did not meaningfully guide routine treatment, because:
- Checkpoint inhibitors showed low activity in unselected ovarian cancer
- No approved indication required PD-L1 testing
- Testing lacked clear clinical consequences
As a result, PD-L1 assessment remained optional, exploratory, and rarely practice-changing.
What the Newly Approved Test Is
The U.S. Food and Drug Administration has granted approval to PD-L1 IHC 22C3 pharmDx as a companion diagnostic assay for patients with:
- Epithelial ovarian carcinoma
- Fallopian tube carcinoma
- Primary peritoneal carcinoma
This approval formally integrates immune biomarker assessment into the therapeutic algorithm of platinum-resistant ovarian cancer, a setting historically characterized by limited precision-guided treatment options.
PD-L1 IHC 22C3 pharmDx is an immunohistochemistry-based assay designed to detect programmed death-ligand 1 (PD-L1) protein expression within tumor tissue and the surrounding immune microenvironment.
Unlike earlier exploratory PD-L1 measurements, this assay applies a standardized scoring methodology — the Combined Positive Score (CPS) — which quantifies PD-L1 expression across:
- Tumor cells
- Tumor-associated lymphocytes
- Macrophages
The CPS is calculated as the number of PD-L1–staining viable tumor and immune cells divided by the total number of viable tumor cells, multiplied by 100, providing a biologically integrated estimate of tumor–immune interactionrather than tumor-cell expression alone.
Within the regulatory framework established by the KEYNOTE-B96 trial, a threshold of CPS ≥ 1 defines the population considered eligible for pembrolizumab-based therapy in combination with paclitaxel, with or without bevacizumab.
Thus, PD-L1 expression measured by this specific assay functions as a predictive biomarker of therapeutic benefit, rather than a purely descriptive or prognostic feature.
Crucially, this distinction elevates PD-L1 IHC 22C3 pharmDx from a laboratory measurement to a treatment-directing regulatory tool:
- It is analytically validated
- Clinically correlated with survival benefit
- Required for therapy selection under FDA labeling
In practical terms, the assay operationalizes the transition from empiric chemotherapy sequencing toward biomarker-guided immuno-oncology in ovarian cancer—marking one of the first instances in this disease where immune checkpoint blockade is linked to a mandatory companion diagnostic.
Clinical Results Supporting Its Use
PD-L1 testing with the 22C3 assay was validated in the KEYNOTE-B96 randomized trial of:
Pembrolizumab + paclitaxel ± bevacizumab
vs
Placebo + paclitaxel ± bevacizumab
Among PD-L1 CPS ≥ 1 tumors:
- Median PFS:
8.3 months vs 7.2 months
HR 0.72 - Median OS:
18.2 months vs 14.0 months
HR 0.76
These data demonstrated a statistically significant survival advantage specifically in the PD-L1–positive population, establishing PD-L1 as a predictive enrichment biomarker in platinum-resistant disease.
FDA Approves Pembrolizumab with Paclitaxel for Platinum-Resistant Ovarian Cancer
What This Test Changes in Clinical Practice
This approval fundamentally shifts PD-L1 testing in ovarian cancer from:
Exploratory biology → Actionable precision oncology
The test now provides:
- A defined population with proven immunotherapy benefit
- A regulatory pathway to pembrolizumab-based treatment
- Integration of immune biomarkers into routine ovarian cancer care
- Movement beyond chemotherapy-only sequencing in platinum-resistant disease
Most importantly, PD-L1 testing transforms immunotherapy from a low-yield experimental option into a biomarker-guided therapeutic strategy.
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