Introduction

 

[Dr Backes] Hello! Thank you for joining us today. I’m Floor Backes, Professor in the Division of Gynecologic Oncology and Director of Gynecologic Cancer Research at The Ohio State University.

 

[Dr Westin] And I’m Dr Shannon Westin, Professor and Clinical Medical Director in the Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center.

 

[Dr Westin] Today we will discuss the US indication for IMFINZI plus CP in patients with primary advanced or recurrent dMMR endometrial cancer, safety data, and physician insights on monitoring and managing select adverse events.

 

[Dr Backes] Before we proceed though, please note that the opinions expressed in this video are solely our own and do not reflect those of AstraZeneca.

 

IMFINZI Endometrial Cancer Indication and Clinical Data

 

[Dr Westin] In June 2024, AstraZeneca received an FDA approval for IMFINZI in combination with carboplatin and paclitaxel followed by single-agent IMFINZI for the treatment of adult patients with primary advanced or recurrent dMMR endometrial cancer.^1,2

 

This approval was based on the prespecified exploratory analysis of progression-free survival in the 95 patients in the dMMR subgroup from the DUO-E trial. IMFINZI plus CP led to a 58% reduction in the risk of progression or death. The median PFS was not reached for patients treated with IMFINZI and CP and 7.0 months for patients treated with CP, with a hazard ratio of 0.42.^1,3

 

DUO-E Study Design

 

[Dr Westin] The DUO-E study was a global, randomized, double-blind, placebo-controlled, Phase III study of 718 patients with advanced or recurrent endometrial cancer.³

 

Patients with recurrent disease were required to have at least a 12-month chemotherapy-free interval to the date of their subsequent relapse with chemotherapy being delivered in the adjuvant setting. All histologies were eligible including carcinosarcomas, except sarcomas.³

 

Within the dMMR subgroup, 95 patients received first-line treatment with CP plus IMFINZI (or placebo) at 1120 mg once every three weeks for 6 cycles, followed by maintenance IMFINZI (or placebo) at 1500 mg once every four weeks. All treatments were given until disease progression or unacceptable toxicity. Note that the IMFINZI dose differs for patients lighter than 30 kg.^1,3

 

One interesting aspect of this design is the relatively short dosing schedule, which brings patients to clinic more often. In my opinion, while patients may prefer to visit the clinic less, these visits provide more opportunities for patients to discuss any concerns with their physician to potentially detect or monitor any AEs to enable early interventions. It is important to ensure patients are counseled on possible AEs that may arise so they can report any concerns immediately.

 

Safety Data in the dMMR Subgroup

 

[Dr Westin] As we know, when determining a treatment plan for a patient, it is important to consider the safety profile of a treatment regimen and any adverse events that may occur. Now, let’s take a look at the safety profile of IMFINZI plus CP in the DUO-E trial.¹

 

Safety data are available for a total of 44 patients with advanced or recurrent dMMR endometrial cancer who received IMFINZI with CP followed by IMFINZI as a single agent until disease progression or unacceptable toxicity. The median duration of exposure to IMFINZI with CP was 14.8 months, with a range of 0.7 to 31.7 months, in the dMMR subgroup.¹

 

Serious adverse reactions occurred in 30% of patients who received IMFINZI with CP.¹

 

Permanent discontinuation of IMFINZI due to adverse reactions occurred in 11% of patients.¹

 

Dosage interruptions of IMFINZI due to adverse reactions occurred in 52% of patients.¹

 

Clinically relevant adverse reactions in less than 10% of patients who received IMFINZI with CP included¹:

• Autoimmune hemolytic anemia

• Colitis

• Immune-mediated thyroiditis

• Infusion-related reaction

• Interstitial lung disease

• Myositis

• Pneumonitis

• Pulmonary embolism and

• Sepsis

 

[Dr Backes] The most common adverse reactions that occurred in more than 20% of patients, including laboratory abnormalities, were peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, decreased magnesium, increased ALT, increased AST, diarrhea, vomiting, cough, decreased potassium, dyspnea, headache, increased alkaline phosphatase, and decreased appetite.¹

 

IMFINZI Dosage Modifications for Adverse Reactions

 

[Dr Backes] When we think about adverse reactions that may arise, it’s important to emphasize that patients and caregivers need counseling on signs and symptoms to look out for so they can detect and quickly report any possible AE. Ideally, it’s best to detect, and monitor, and manage any Grade 1 AE before it can progress to a higher grade, where it can become more challenging to mitigate.¹

 

Note that AEs can happen during or after treatment, underscoring the importance of educating patients and caregivers to look out for new or worsening symptoms.¹

 

If AEs are detected, dose reductions for IMFINZI are not recommended. In general, for severe Grade 3 immune-mediated adverse reactions, IMFINZI should be withheld. For any immune-mediated, life-threatening Grade 4 or recurrent severe Grade 3 immune-mediated adverse reactions that require systemic immunotherapy treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating corticosteroid, in that case IMFINZI should be permanently discontinued. It’s important to consider the recommended dosage modifications for specific adverse reactions noted in the IMFINZI prescribing information (which is shown here).¹

 

Immune-Mediated Adverse Reactions

 

[Dr Westin] Now that we’ve covered the key DUO-E safety data in the dMMR subgroup, we would like to discuss immune-mediated adverse reactions that may be relevant for this patient population.

 

IMFINZI is an immune checkpoint inhibitor that blocks the PD-1/PD-L1 pathway and removes inhibition of the immune response, which potentially breaks peripheral tolerance and may induce immune-mediated adverse reactions.¹

 

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. These may include immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, solid organ transplant rejection, and immune-mediated pancreatitis.¹

 

[Dr Backes] Overall, identifying and managing immune-mediated adverse reactions is essential to help ensure the safe use of IMFINZI. The healthcare team should monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions.¹

 

In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy with 1 to 2 mg/kg/day prednisone or equivalent until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid treatment.¹

 

Patients should be encouraged to report any new symptoms quickly so clinicians can evaluate and decide on a course of action, which may include monitoring, a workup to exclude any alternative conditions, medical management, or evaluating whether IMFINZI may need to be withheld or discontinued.¹

 

In addition, it’s important to evaluate the patient’s liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment with IMFINZI.¹

 

[Dr Westin] Now that we’ve described the monitoring and management strategies for immune-mediated AEs, let’s discuss 3 specific AEs further. Specifically, we would like to focus on dermatitis or rash, thyroid-related adverse reactions, and pneumonitis.

 

Immune-Mediated Rash

 

[Dr Westin] First, let’s discuss immune-mediated rash or dermatitis. We thought it would be valuable to discuss this AE, as rash is one of the most common serious adverse reactions, with 4.5% of patients in the clinical trial experiencing the AE, and it also led to the highest percentage of permanent discontinuations of IMFINZI in 4.5% of patients who received IMFINZI with CP in the DUO-E trial.¹

 

[Dr Backes] In addition, exfoliative dermatitis, including Stevens-Johnson Syndrome, drug rash with eosinophilia and systemic symptoms, or DRESS, and toxic epidermal necrolysis, or TEN, has occurred with PD-1/PD-L1 blocking antibodies.¹

 

Usually what we would do is monitor skin-related symptoms such as rash, itching, skin blistering or peeling, painful sores or ulcers in the mouth or nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodes.¹

 

If mild to moderate non-exfoliative rashes arise, topical emollients and/or topical corticosteroids may be adequate to treat.¹

 

Depending on the severity of the rash, the physician may need to withhold or permanently discontinue IMFINZI.¹

 

Immune-Mediated Thyroid Disorders

 

[Dr Westin] The second group of AEs we’d like to discuss are immune-mediated thyroid disorders. For example, hypothyroidism can arise and has been reported in 11% of patients in the dMMR subgroup in DUO-E that received IMFINZI and CP.¹

 

While this is not one of the most common AEs, we thought it would be interesting to discuss for this exact reason, as physicians may be less familiar with managing and monitoring thyroid-related AEs.

 

It is known that IMFINZI can cause immune-mediated thyroid disorders. Notably, thyroiditis can present with or without endocrinopathy, and hypothyroidism can follow hyperthyroidism. Therefore, it’s important to monitor thyroid function prior to and periodically during treatment.¹

 

[Dr Backes] There are a number of endocrine symptoms to monitor that may be related to thyroid function issues, such as unusual headaches, exhaustion, changes in weight or appetite, and more.¹

 

If hypothyroidism arises, hormone replacement therapy should be initiated. If hyperthyroidism arises, medical management should be initiated.¹

 

Depending on the severity, IMFINZI should be withheld until the patient is clinically stable or should be permanently discontinued.¹

 

Immune-Mediated Pneumonitis

 

[Dr Westin] The last immune-mediated AE we’d like to discuss is pneumonitis, which can be difficult to diagnose and can be serious.⁴

 

We know that IMFINZI can cause immune-mediated pneumonitis.¹ In the DUO-E study, the presence of this AE required dosage interruptions of IMFINZI in 4.5% of patients who received IMFINZI with CP.¹

 

[Dr Backes] In my practice, my course of action is to evaluate and monitor pulmonary symptoms including cough, shortness of breath, and chest pain.¹

 

And if pneumonitis is suspected, I refer the patient to radiographic imaging or for further evaluations.⁵ One radiologic pattern to look for in computed tomography scans is opacities in ground-glass infiltrates.⁴

 

If Grade 2 or higher pneumonitis is detected, I would withhold IMFINZI treatment. I’d resume IMFINZI in patients with complete or partial resolution (or Grade 0 to 1) after corticosteroid taper. If there was no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dose to 10 mg of prednisone or less per day (or equivalent) within 12 weeks of initiating corticosteroids, I’d permanently discontinue IMFINZI.¹

 

If Grade 3 or 4 pneumonitis is detected, then I would permanently discontinue IMFINZI.¹

 

[Dr Backes] As a reminder, the CTCAE provides unique clinical descriptions of the severity for each AE based on general guidelines. You can see the importance of identifying and treating pneumonitis as early as possible before symptoms become severe. It can be difficult to reverse pneumonitis once it progresses and the consequences are serious.⁶

 

DUO-E Safety Key Points

 

[Dr Westin] On behalf of Dr Backes and myself, I would like to thank you for tuning in today. I would like to leave you with a few key points to summarize this discussion.

 

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue.¹

 

Early identification of immune-mediated adverse reactions is essential to ensure safe use of IMFINZI.¹

 

It is important to monitor for AEs during and following treatment and have a grade-specific plan in place to help manage AEs if they arise.⁷

IMPORTANT SAFETY INFORMATION

 

There are no contraindications for IMFINZI^® (durvalumab).

 

Immune-Mediated Adverse Reactions

Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function 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. Withhold or permanently discontinue IMFINZI depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

 

Immune-Mediated Pneumonitis

IMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

 

Immune-Mediated Colitis

IMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

 

Immune-Mediated Hepatitis

IMFINZI can cause immune-mediated hepatitis.

 

Immune-Mediated Endocrinopathies

• Adrenal Insufficiency: IMFINZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.

• Hypophysitis: IMFINZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated.

• Thyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism): IMFINZI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.

  • IMFINZI with Carboplatin and Paclitaxel

    • Immune-mediated hypothyroidism occurred in 14% (34/235) of patients receiving IMFINZI in combination with carboplatin and paclitaxel.

• Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated.

 

Immune-Mediated Nephritis with Renal Dysfunction

IMFINZI can cause immune-mediated nephritis.

 

Immune-Mediated Dermatology Reactions

IMFINZI can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.

 

Other Immune-Mediated Adverse Reactions

The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI or were reported with the use of other PD-1/PD-L1 blocking antibodies.

• Cardiac/vascular: Myocarditis, pericarditis, vasculitis.

• Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.

• Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.

• Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.

• Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic.

• Endocrine: Hypoparathyroidism.

• Other (hematologic/immune): 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

IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses.

 

Complications of Allogeneic HSCT after IMFINZI

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.

 

Embryo-Fetal Toxicity

Based on their mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and advise them to use effective contraception during treatment with IMFINZI and for 3 months after the last dose of IMFINZI.

 

Lactation

There is no information regarding the presence of IMFINZI in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI, advise women not to breastfeed during treatment and for 3 months after the last dose.

 

Adverse Reactions

• In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent (n=44), the most common adverse reactions, including laboratory abnormalities (occurring in >20% of patients) were peripheral neuropathy (61%), musculoskeletal pain (59%), nausea (59%), alopecia (52%), fatigue (41%), abdominal pain (39%), constipation (39%), rash (39%), decreased magnesium (36%), increased ALT (32%), increased AST (30%), diarrhea (27%), vomiting (27%), cough (27%), decreased potassium (25%), dyspnea (25%), headache (23%), increased alkaline phosphatase (20%), and decreased appetite (18%). The most common Grade 3 or 4 adverse reactions (≥3%) were constipation (4.5%) and fatigue (4.5%).

• In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent (n=44), permanent discontinuation of IMFINZI due to adverse reactions occurred in 11% of patients. Serious adverse reactions occurred in 30% of patients who received IMFINZI with carboplatin and paclitaxel; the most common serious adverse reactions (≥4%) were constipation (4.5%) and rash (4.5%).

 

The safety and effectiveness of IMFINZI has not been established in pediatric patients.

 

Indication:

IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test.

 

Please see Full Prescribing Information including Medication Guide for IMFINZI at IMFINZIhcp.com.

 

You are encouraged to report side effects related to AstraZeneca products by calling 1-800-236-9933. If you prefer to report these to the FDA, please call 1-800-FDA-1088.

 

©2025 AstraZeneca. All rights reserved.

US-93745 Last Updated 5/25

1. IMFINZI^® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2025.

2. AstraZeneca. IMFINZI plus chemotherapy approved in the US for mismatch repair deficient advanced or recurrent endometrial cancer. Accessed March 2025. https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-approved-in-the-us-for-endometrial-cancer.html

3. Westin SN, Moore K, Chon HS, et al. Durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab with or without olaparib as first-line treatment for advanced endometrial cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024;42(3):283-299.