What Oncology Pharmacists Should Know About the Evolution of Frontline Treatment in Primary Advanced Endometrial Cancer: Perspectives from Jennifer MacDonald, Oncology Clinical Pharmacy Specialist

This article is sponsored by GSK

Treatment decision-making in endometrial cancer is becoming increasingly nuanced given meaningful shifts in the frontline setting. As the most common gynecologic malignancy in the U.S. and with incidence and mortality rates that continue to rise,^1,2 there remains a clear need to improve patient outcomes.

While carboplatin plus paclitaxel (CP) has long served as the standard frontline regimen for primary advanced or recurrent endometrial cancer, the emergence of immunotherapy-based combinations has begun to reshape expectations.³

This shift is supported by the underlying biology of endometrial cancer, which has a relatively high prevalence of mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) tumors. PD-1/PD-L1 immune checkpoint inhibitors, which work by restoring antitumor immune activity, have demonstrated significant activity in dMMR/MSI-H tumors compared with mismatch repair proficient/microsatellite stable (MMRp/MSS) tumors. However, the majority of patients with endometrial cancer have have the MMRp/MSS biomarker, which is often less responsive to immunotherapy alone. This has driven the development of combination strategies, such as pairing checkpoint inhibitors with chemotherapy, to extend clinical benefit to an overall population of patients with MMRp/MSS and dMMR/MSI-H biomarker status.^4,5

As the landscape evolves, oncology pharmacists play a central role in translating clinical evidence into real-world decisions — helping guide regimen selection, formulary use and multidisciplinary discussions across care teams.

Interpreting Clinical Endpoints in the Evolving Frontline Landscape

As frontline treatment options expand in primary advanced or recurrent endometrial cancer, oncology pharmacists are increasingly tasked with interpreting a more complex evidence base, including understanding the strengths and limitations of different clinical endpoints. Response rates and progression-free survival (PFS) can provide earlier indications of potential treatment benefit. However, they do not necessarily predict improvements in overall survival (OS).⁶ This distinction has taken on even greater relevance as immunotherapy-based combinations introduce the potential for additional clinical benefit.⁷

“Overall survival is one of the more meaningful endpoints we have and is critical for guiding treatment selection,” said Jennifer MacDonald, PharmD, BCOP, Oncology Clinical Pharmacy Specialist. “I frequently discuss with both providers and patients the OS results from clinical studies and whether the endpoint was adequately powered to detect a treatment difference with the comparator.”

As these considerations guide frontline treatment decisions, emerging OS data are helping to further shape expectations for immunotherapy-based combinations in this setting.

Phase 3 Data May Help Inform Frontline Treatment Considerations

Among immunotherapy-based combinations, JEMPERLI (dostarlimab-gxly) injection 500 mg, a programmed death receptor-1 (PD-1)-blocking antibody, has been evaluated in combination with CP in the phase 3 RUBY trial in patients with primary advanced or recurrent endometrial cancer.

Indications

• JEMPERLI, in combination with 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 Oncology Pharmacists

• Dosing: 500 mg every 3 weeks during combination therapy with JEMPERLI + CP, transitioning to 1,000 mg every 6 weeks as monotherapy with JEMPERLI.
• Administration: Administer JEMPERLI prior to CP when given on the same day.
• Monitoring and management of adverse reactions: Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1–blocking antibodies. Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Dosage modifications for specific adverse reactions can be found in Section 2.3 of the JEMPERLI Prescribing Information.

A phase 3, randomized, double-blind trial of patients with primary advanced or recurrent EC
(N=494, all-comers) who were randomized 1:1 to JEMPERLI + CP or placebo + CP every 3 weeks for 6 cycles, followed by JEMPERLI or placebo every 6 weeks, respectively, until disease progression, unacceptable toxicity, or up to 3 years. Major efficacy endpoints were investigator-assessed PFS by RECIST v1.1 in the dMMR/MSI-H and all-comers populations, and OS in all-comers (dMMR/MSI-H: n=122/494; MMRp/MSS: n=372/494).⁸

Results from RUBY demonstrated statistically significant improvements in both PFS and OS with JEMPERLI plus CP vs placebo plus CP in all‑comers. Median PFS was 11.8 months (95% CI: 9.6, 17.1) vs 7.9 months (95% CI: 7.6, 9.5), translating to a 36% reduction in the risk of progression or death (HR: 0.64; 95% 0.51, 0.80; P<0.0001). Median OS was 44.6 months (95% CI: 32.6, NR) vs 28.2 months (95% CI: 22.1, 35.6), corresponding to a 16.4‑month improvement and a 31% reduction in the risk of death (HR: 0.69; 95% 0.54, 0.89; P=0.002).

Clinical outcomes varied across the dMMR/MSI-H and MMRp/MSS subgroups. In the dMMR/MSI-H subgroup, median PFS was 30.3 months (95% CI: 11.8, NR) with JEMPERLI + CP vs 7.7 months (95% CI: 5.6, 9.7) with placebo + CP (HR: 0.29; 95% CI: 0.17, 0.50, P<0.0001). In a prespecified exploratory analysis of the dMMR/MSI-H subgroup, median OS was not reached with JEMPERLI + CP vs 30.8 months (95% CI: 18.7, NR) with CP alone (HR=0.34; 95% CI: 0.18, 0.62). Prespecified exploratory analyses in the MMRp/MSS subgroup showed a median OS of 32.5 months (95% CI: 28.6, NR) with JEMPERLI + CP vs 28.2 months (95% CI: 21.9, 36.1) with placebo + CP, and a median PFS of 9.8 months (95% CI: 9.0, 12.6) vs 7.9 months (95% CI: 7.6, 9.8), respectively. These exploratory analyses were not powered to detect treatment differences, and results are descriptive.

“One important aspect of RUBY was the intentional inclusion of patients with challenging histologies such as carcinosarcoma as well as individuals with advanced-stage disease who did not have measurable disease,” said MacDonald. “Approximately 9% of trial participants had carcinosarcoma, which speaks to the diversity of disease characteristics included in the study. Additionally, the inclusion of patients without measurable disease is a scenario commonly seen in clinical practice following surgery.”

These findings have informed regulatory decisions, including expansion of the FDA approval in 2024 of JEMPERLI in combination with CP from use in patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer to use in all adult patients with primary advanced or recurrent endometrial cancer, regardless of biomarker status.⁸

In primary advanced or recurrent endometrial cancer, JEMPERLI + CP is the only FDA-approved immuno-oncology regimen that was proven with a statistically significant overall survival benefit for all-comers compared to CP alone. It also has the longest median follow-up for an FDA-approved immunotherapy combination in primary advanced and recurrent EC for the all-comers and dMMR/MSI-H populations to date. These results help enable more informed decision-making regarding the use of immunotherapy-based combinations, such as JEMPERLI + CP, as first line treatment in this setting.

“Having a frontline option approved regardless of biomarker status can be impactful," said MacDonald. "It means we don't have to wait for biomarker testing results before initiating treatment.”

JEMPERLI plus CP offers a well-established safety profile. In patients receiving JEMPERLI and CP, 19% permanently discontinued JEMPERLI due to adverse reactions and 37% required treatment interruptions, reflecting the need for ongoing monitoring and management of adverse reactions.⁸

MacDonald added: “With immunotherapy, we do see additional side effects beyond chemotherapy that healthcare teams should be aware of and counsel their patients on. Immune-mediated adverse reactions should be closely monitored. These reactions can sometimes be delayed, so ongoing vigilance and counseling is key.”

The Oncology Pharmacist as a Partner in Care

In primary advanced endometrial cancer, clinical trial data are often interpreted in the context of individual patient needs and real-world practice. Given the heterogeneity of disease, this includes assessing which patients may be likely to benefit and how outcomes may vary across subgroups. Survival data, in particular, are considered alongside factors such as toxicity and treatment burden, helping to inform more nuanced discussions with care teams and patients around treatment selection.

Oncology pharmacists play a key role in operationalizing these decisions in practice, including integrating additional regimens into electronic health records (EHRs) to support standardized, evidence-based care and educating patients on treatment considerations and adverse event management, as well as supporting staff training.

“I bring data, like from the RUBY clinical trial, to our monthly division meetings and quarterly journal clubs where we discuss how these trials may inform clinical practice and where they fit into therapy,” MacDonald explained. “I come prepared with my own interpretation so I can contribute meaningfully while staying open to different perspectives.”

This collaborative approach extends directly into patient care, where pharmacists help shape therapy selection through molecular profiling and precision oncology. “We review pathology, molecular, and genetic data to determine the most appropriate treatment and actively participate in tumor boards to guide those discussions,” she said.

Beyond clinical decision-making, oncology pharmacists also play a key role in formulary and access discussions, advocating for the inclusion of multiple immunotherapy options to reflect differences in trial populations and clinical use. “It’s critical to understand the nuances in the data and ensure the right therapies are available for the right patients,” MacDonald shared. When evaluating different regimens, pharmacists take a comprehensive view — considering trial design, inclusion criteria, toxicity, and patient goals — to balance efficacy with patient-centered care.

“It’s about knowing the data inside and out and anticipating how treatment decisions can impact patients,” MacDonald noted. Ultimately, staying current and engaged is a shared effort. “It’s a collaborative process — I learn from colleagues, primary literature, medical science liaisons, and my patients. You don’t have to be an expert right away; you start using the therapy, monitor closely, and refine your approach. It’s truly a team effort.”

Advancing Possibilities in Endometrial Cancer Care

The evolution of the frontline treatment landscape in primary advanced or recurrent endometrial cancer represents meaningful progress for patients and underscores the need for clinicians and care teams to stay current on emerging data. As the science continues to advance, there is also growing attention to how factors such as biomarkers may help inform treatment decisions.

“I think one of the most exciting aspects of where oncology is heading is that we’re finally seeing more options for patients and meaningful improvements in outcomes in endometrial cancer. These additional options are especially important for higher-risk histologies and underserved populations, where historically we haven’t made as much progress.”

To learn more about how pharmacists are dispensing the possibility for more time with JEMPERLI + CP vs CP alone, 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-DSTCOCO260001 July 2026
Produced in USA.

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