Precision in Practice: Biomarker Testing and Treatment Selection in Primary Advanced or Recurrent Endometrial Cancer

Insights from Jennifer MacDonald, Oncology Clinical Pharmacy Specialist

This article is sponsored by GSK

As frontline treatment options and emerging data continue to reshape care in primary advanced or recurrent endometrial cancer, the next challenge is determining which patients may be more likely to benefit. That shift has made biomarker testing a critical component of treatment selection and positioned oncology pharmacists at the center of precision oncology in practice, helping ensure treatment decisions are informed by both biomarker insights and the available clinical evidence.

Molecular Classification Has Changed the Treatment Paradigm

Endometrial cancer was once defined primarily by histology and grade, but molecular classification now provides a deeper understanding of tumor biology and treatment responsiveness.¹ Among the most clinically meaningful distinctions is mismatch repair (MMR) status. Tumors that are mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI‑H) carry a higher mutational burden and are more immunogenic than mismatch repair-proficient/microsatellite stable (pMMR/MSS) tumors, which underlies their sensitivity to immune checkpoint inhibition.¹

Because of this, molecular testing—especially for MMR status—has become a foundational step in treatment planning. Approximately 30 percent of endometrial tumors are dMMR/MSI-H, making timely biomarker testing essential to identifying patients whose disease biology may influence treatment selection.¹ Guidelines now recommend universal MMR testing for all endometrial cancers, reflecting its importance not only for therapy selection, but also for providing valuable information that may inform broader patient care considerations.²

Why Biomarker Testing Is Non‑Negotiable

In primary advanced or recurrent endometrial cancer, biomarker status can directly inform treatment selection, yet real‑world barriers still limit timely and consistent testing.

Jennifer MacDonald, Oncology Clinical Pharmacy Specialist, describes the challenges as multifactorial: “Access to in‑house vs send‑out testing, staffing constraints in pathology, and inconsistent awareness of why testing needs to be done upfront—all of these contribute. Some providers still wait until recurrence to test, but that’s slowly changing as more therapies require biomarker confirmation.”

Even in well‑coordinated systems, delays can disrupt care. “Sometimes we start therapy and delay immunotherapy selection while waiting for results. It may also delay clinical trial enrollment.” Reporting workflows can add another layer of complexity. “Results may come back without the treating team being notified. We need more transparent reporting—not just waiting for uploads or checking old results to see if new ones populated.”

Despite these challenges, the need for MMR testing is unmistakable. “It requires standardization and collaboration across multiple departments, which can be hard with limited resources. But these results are crucial to the goal of optimizing outcomes in a disease with rising incidence and mortality.”

Oncology pharmacists play a pivotal role in closing these gaps by:

• Confirming biomarker status in endometrial cancer patients, especially in those with primary advanced or recurrent disease
• Ensuring pathology reports include MMR results, not just histologic findings
• Educating care teams on testing requirements and the implications of having dMMR/MSI‑H vs pMMR/MSS biomarkers
• Supporting prior authorization and reimbursement processes tied to biomarker‑dependent therapies
• Standardizing testing workflows and ensuring results are readily available to support timely treatment decisions informed by each patient's tumor biology

By ensuring testing is ordered correctly, completed on time, and clearly reported, pharmacists help guarantee that treatment decisions align with both tumor biology and the evidence guiding modern endometrial cancer care.

Using Biomarkers to Drive Evidence‑Based Therapy Selection

Once pathology results are available, pharmacists help colleagues make informed treatment decisions by ensuring biomarker results meaningfully shape the treatment plan. “I challenge treatment selection both before and after results come back,” says MacDonald. “These markers are important when choosing therapies.” This may require re-evaluating treatment plans, particularly for patients with high‑risk histologies such as serous or carcinosarcoma, where pharmacists must balance efficacy, toxicity, and cost.

While treatment approaches differ across molecular subgroups, biomarker status helps guide therapy selection and interpretation of clinical outcomes for both dMMR/MSI-H and pMMR/MSS disease. As treatment decisions become increasingly personalized, molecular testing is no longer strictly diagnostic, it is a tool for delivering more precise, individualized care.

The challenge is no longer whether molecular testing should be performed, but ensuring results are available, visible, and actionable when treatment decisions are being made. Pharmacists help teams interpret biomarker results in the context of evolving efficacy and safety data. “The clinical data can vary across subgroups,” MacDonald emphasizes.³ “And these therapies come with serious, sometimes life‑threatening immune‑related adverse reactions. If you take a one‑size‑fits‑all approach, can you justify those risks? Patients trust us to interpret the data responsibly.”

Biomarker Testing Enables More Personalized Treatment Decisions

For patients with endometrial cancer, advances in immunotherapy have reinforced the importance of timely biomarker testing and molecular classification.^2,3 As insights into molecular subgroups continue to evolve, understanding tumor biology has become an essential component of treatment planning.^2,3

“It's had an important impact on the treatment landscape,” MacDonald explains. “Recognizing the differences between molecular subgroups reinforces why obtaining biomarker results early is such an important part of treatment planning. These results help us make more informed treatment decisions and have better conversations with patients about their options.”

The growing role of biomarker-guided treatment in primary advanced or recurrent endometrial cancer is reflected in therapies such as JEMPERLI (dostarlimab-gxly) injection 500 mg, underscoring the importance of understanding tumor biology early in the treatment journey.^3,4

Indications

• JEMPERLI, in combination with carboplatin and paclitaxel (CP), followed by JEMPERLI as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC).
• JEMPERLI, as a single agent, is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced EC, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen in any setting and are not candidates for curative surgery or radiation.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

• Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue and can occur at any time during or after treatment with a PD-1/PD-L1–blocking antibody, including JEMPERLI.
• Monitor closely for signs and symptoms of immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. For suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

See full Important Safety Information below.

Practical Considerations for PD‑1–Based Regimens

Pharmacists play a central role in ensuring the appropriate use of PD‑1–based regimens across the care team. They design electronic medical record workflows that highlight biomarker results clearly so treatment decisions align with tumor biology.

“I work with seven attendings, and we meet frequently to standardize what treatment we offer and how it is used. I also run journal clubs and education sessions to keep the team aligned on evolving evidence,” MacDonald explains.

Beyond standardizing practice, pharmacists serve as key educators within the multidisciplinary team, translating emerging clinical evidence into practical treatment considerations for providers and staff. That shifts more responsibility onto pharmacists, who manage follow‑ups between visits, monitor for immune‑related toxicities, and coordinate care across specialties. “We’re often more accessible than physicians who may be in the OR,” MacDonald adds. Beyond treatment selection, pharmacists remain involved throughout the treatment journey, helping patients and care teams navigate monitoring, adverse event management, and evolving treatment decisions over time. This combination of operational design, clinical oversight, and accessibility makes pharmacists the steady point of contact throughout multiple courses of immunotherapy, ensuring continuity, monitoring, and timely intervention as treatment may extend over many months.

Supporting Management and Monitoring of Adverse Reactions Across the Care Continuum

Pharmacists also play an important role in monitoring for immune-related adverse reactions that may emerge during therapy or even after treatment discontinuation, helping ensure timely recognition and intervention.⁴ They are often the first to detect subtle changes in labs or symptoms that signal emerging toxicity and are central to educating patients on early warning signs, supporting steroid initiation and tapering, coordinating with endocrinology, gastroenterology, pulmonology, and ensuring smooth transitions between inpatient and outpatient care. “For women thrown into menopause, this could also include the proper mental health coordination,” MacDonald adds. “Early recognition and management of adverse reactions may help patients remain on therapy when appropriate and reduce unnecessary treatment interruptions. That's the key to supporting patients throughout treatment.”

Their role extends beyond toxicity management into improving access and standardization, particularly in community oncology. Pharmacists streamline testing workflows, ensure biomarker results are obtained and documented, and reinforce the importance of biomarker‑guided therapy in settings where providers manage many tumor types and may struggle to keep pace with rapidly evolving data.

“In the community, providers cover so many tumor types that keeping up with rapidly changing data is hard,” MacDonald explains. “If pharmacists standardize testing workflows, review results, and ensure documentation, we can dramatically improve outcomes. We’re trained for this—we should be at the center of these standardizations.”

Where Precision Meets Practice

Precision oncology succeeds only when evidence is operationalized. In primary advanced or recurrent endometrial cancer, biomarker testing can transform data into actionable care decisions.

As medication experts and key clinical partners, oncology pharmacists sit at the intersection of data interpretation, workflow execution, and patient safety, helping colleagues make informed treatment decisions and ensuring that the right patients are identified, treated, and supported throughout increasingly complex care pathways.

As treatment options continue to evolve, pharmacists can be key players in translating molecular insight into personalized patient care, turning precision science into precision practice.

Your treatment recommendations can make a real difference in your patients’ lives. To learn more about what possibilities pharmacists can dispense for appropriate patients, visit JEMPERLIHCP.com.

Important Safety Information

Severe and Fatal Immune-Mediated Adverse Reactions

• Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue and can occur at any time during or after treatment with a PD-1/PD-L1–blocking antibody, including JEMPERLI.
• Monitor closely for signs and symptoms of immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. For suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
• Based on the severity of the adverse reaction, withhold or permanently discontinue JEMPERLI. In general, if JEMPERLI requires interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) until improvement to ≤Grade 1. Upon improvement to ≤Grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroids.

Immune-Mediated Pneumonitis

• JEMPERLI can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Pneumonitis occurred in 2.3% (14/605) of patients, including Grade 2 (1.3%), Grade 3 (0.8%), and Grade 4 (0.2%) pneumonitis.

Immune-Mediated Colitis

• Colitis occurred in 1.3% (8/605) of patients, including Grade 2 (0.7%) and Grade 3 (0.7%) adverse reactions. Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis. In such cases, consider repeating infectious workup to exclude alternative etiologies.

Immune-Mediated Hepatitis

• JEMPERLI can cause immune-mediated hepatitis, which can be fatal. Grade 3 hepatitis occurred in 0.5% (3/605) of patients.

Immune-Mediated Endocrinopathies

• Adrenal Insufficiency
  • Adrenal insufficiency occurred in 1.2% (7/605) of patients, including Grade 2 (0.5%) and Grade 3 (0.7%). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
• Hypophysitis
  • JEMPERLI can cause immune-mediated hypophysitis. Grade 3 hypophysitis occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypophysitis occurred in 0.2% (1/605) of patients receiving JEMPERLI as a single agent. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
• Thyroid Disorders
  • Grade 2 thyroiditis occurred in 0.5% (3/605) of patients. Grade 2 hypothyroidism occurred in 12% (30/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypothyroidism occurred in 8% (46/605) of patients receiving JEMPERLI as a single agent. Hyperthyroidism occurred in 3.3% (8/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel, including Grade 2 (2.9%) and Grade 3 (0.4%). Hyperthyroidism occurred in 2.3% (14/605) of patients receiving JEMPERLI as a single agent, including Grade 2 (2.1%) and Grade 3 (0.2%). Initiate thyroid hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.
• Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis
  • JEMPERLI can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Grade 3 type 1 diabetes mellitus occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 3 type 1 diabetes mellitus occurred in 0.2% (1/605) of patients receiving JEMPERLI as a single agent. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.

Immune-Mediated Nephritis with Renal Dysfunction

• JEMPERLI can cause immune-mediated nephritis, which can be fatal. Grade 2 nephritis, including tubulointerstitial nephritis, occurred in 0.5% (3/605) of patients.

Immune-Mediated Dermatologic Adverse Reactions

• JEMPERLI can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD-1/PD-L1–blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently discontinue JEMPERLI depending on severity.

Other Immune-Mediated Adverse Reactions

• The following clinically significant immune-mediated adverse reactions occurred in <1% of the 605 patients treated with JEMPERLI or were reported with the use of other PD-1/PD-L1–blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.
  • Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy
  • Cardiac/Vascular: Myocarditis, pericarditis, vasculitis
  • Ocular: Uveitis, iritis, other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur
  • Gastrointestinal: Pancreatitis, including increases in serum amylase and lipase levels, gastritis, duodenitis
  • Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica
  • Endocrine: Hypoparathyroidism
  • Other (Hematologic/Immune): Autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection

Infusion-Related Reactions

• Severe or life-threatening infusion-related reactions have been reported with PD-1/PD-L1–blocking antibodies. Severe infusion-related reactions (Grade 3) occurred in 0.2% (1/605) of patients receiving JEMPERLI. Monitor patients for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion or permanently discontinue JEMPERLI based on severity of reaction.

Complications of Allogeneic HSCT

• Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after treatment with a PD-1/PD-L1–blocking antibody, which may occur despite intervening therapy. Monitor patients closely for transplant-related complications and intervene promptly.

Embryo-Fetal Toxicity and Lactation

• Based on its mechanism of action, JEMPERLI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after their last dose. Because of the potential for serious adverse reactions from JEMPERLI in a breastfed child, advise women not to breastfeed during treatment with JEMPERLI and for 4 months after their last dose.

Common Adverse Reactions

The most common adverse reactions (≥20%), including laboratory abnormalities, in patients with EC who received JEMPERLI in combination with carboplatin and paclitaxel were decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, decreased platelets, increased glucose, decreased lymphocytes, decreased magnesium, decreased neutrophils, increased AST, arthralgia, rash, constipation, diarrhea, increased ALT, decreased potassium, decreased albumin, decreased sodium, increased alkaline phosphatase, abdominal pain, dyspnea, decreased appetite, increased amylase, decreased phosphate, urinary tract infection, and vomiting.

The most common adverse reactions (≥20%) in patients with dMMR EC who received JEMPERLI as a single agent were fatigue/asthenia, anemia, nausea, diarrhea, constipation, vomiting, and rash. The most common Grade 3 or 4 laboratory abnormalities (>2%) were decreased lymphocytes, decreased sodium, increased alanine aminotransferase, increased creatinine, decreased neutrophils, decreased albumin, and increased alkaline phosphatase.

Please see full Prescribing Information, including Medication Guide.

Jennifer MacDonald is a board-certified oncology pharmacist and has been compensated by GSK for her participation in this article.

Intended for US healthcare professionals.
Trademarks are owned by or licensed to the GSK group of companies.
©2026 GSK or licensor.
PMUS-DSTCOCO260006 September 2026
Produced in USA.

References:

1. Makker V, et al. Nat Rev Dis Primers. 2021;7(1):88. doi:10.1038/s41572-021-00324-8.
2. Concin N, et al. Int J Gynecol Cancer. 2021;31(1):12-39. doi:10.1136/ijgc-2020-002230.
3. Powell MA, et al. Ann Oncol. 2024;35(8):728-738. doi:10.1016/j.annonc.2024.05.546
4. JEMPERLI. Prescribing Information. GSK; 2025.