View this email as a web page

Prescribing Information

Important Safety Information

Indication

See the 3-YEAR ES-SCLC data


	IMFINZI + EP: The ONLY FDA‑approved IO combination in first‑line ES‑SCLC with 3‑YEAR overall survival data from a randomized Phase III study^1-3

	The CASPIAN 3‑year exploratory analysis is the longest median follow‑up reported to date for a randomized Phase III study of an FDA‑approved IO combination with chemotherapy in first‑line ES‑SCLC.^1-3



	Indication:

	IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first‑line treatment of adult patients with extensive-stage small cell lung cancer (ES‑SCLC).

	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.

	Please scroll for additional Important Safety Information.

	The planned exploratory 3-year overall survival analysis was not tested for statistical significance¹

	At the time of the 3-year analysis, mOS was 12.9 months (95% CI, ‌1‌1‌.‌3‌‑‌1‌4.‌7) with IMFINZI + EP vs 10.5 months (95% CI, ‌9.‌3-‌1‌1.‌2) with EP alone¹

Durvalumab (IMFINZI®) + etoposide with either cisplatin or carboplatin is a Category 1, preferred treatment option for first-line ES-SCLC

•	NCCN recognizes that durvalumab (IMFINZI^®) + EP presented updated data from a 3-year analysis⁵

Safety and tolerability

•	Serious adverse reactions occurred in 31% of patients receiving IMFINZI + EP at the interim analysis and in 32% of patients receiving IMFINZI + EP at the 3-year analysis^1,4

•	The most frequent serious adverse reactions reported in ≥1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and chronic obstructive pulmonary disease (1.1%)⁴

•	The most common adverse reactions (occurring in ≥20% of patients) were nausea, fatigue/asthenia, and alopecia⁴

•	Discontinuation rates were the same with IMFINZI + EP and EP alone (9% in both arms)⁶

•	Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI + EP. These include pancytopenia, sepsis, septic shock, pulmonary artery thrombosis, pulmonary embolism, and hepatitis (1 patient each) and sudden death (2 patients)⁴

CI=confidence interval; EP=etoposide and either carboplatin or cisplatin; ES-SCLC=extensive-stage small cell lung cancer; HR=hazard ratio; IO=immuno-oncology; mOS=median overall survival; NCCN=National Comprehensive Cancer Network^® (NCCN^®); OS=overall survival; Q3W=every 3 weeks; Q4W=every 4 weeks.


*	The CASPIAN study was an open-label, multicenter, Phase III study of 805 treatment-naïve patients with ES-SCLC who were randomized 1:1:1 between 3 arms. Patients received IMFINZI 1500 mg plus either carboplatin or cisplatin and etoposide Q3W (n=268) for 4 cycles, followed by IMFINZI 1500 mg Q4W until disease progression or unacceptable toxicity or either carboplatin or cisplatin and etoposide Q3W (n=269) for 4 to 6 cycles. The third arm was IMFINZI plus an Investigational Agent and EP followed by IMFINZI maintenance (n=268). FDA approval was based on results from the planned interim analysis of the IMFINZI + EP and EP alone arms. Overall survival was the primary endpoint. At the time of the planned interim overall survival analysis with a median duration of follow-up of 14.2 months, mOS was 13 months (95% CI, ‌1‌1‌.‌5-‌1‌4.‌8) with IMFINZI + EP vs 10.3 months (95% CI, ‌9.‌3-‌1‌1.‌2) with EP alone (HR=0.73; 95% CI, 0.59-0.91; P=0.0047).^4,6

^†	The planned exploratory 3-year OS analysis was conducted at ~3 years after the last patient was randomized, and was not tested for statistical significance. OS rates at 12, 24, and 36 months are the estimated proportion of patients alive based on the 3-year analysis.^1,6

^‡	NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

^§	See the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for detailed recommendations, including other preferred treatment options.⁵

See the 3-YEAR CASPIAN data

IMPORTANT SAFETY INFORMATION (continued)

Immune-Mediated Adverse Reactions (continued)

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. In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy.

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 colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.

Immune-Mediated Hepatitis

IMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions.

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. Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.

•	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. Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI.

•	Thyroid Disorders: 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.

•	Thyroiditis: Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.

•	Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI.

•	Hypothyroidism: Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.

•	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. Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI.

Immune-Mediated Nephritis with Renal Dysfunction

IMFINZI can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.

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 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.

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.

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. Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.

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 its 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 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 extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%), and alopecia (31%). The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%).

•	In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy.

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

Please see additional Important Safety Information throughout and Full Prescribing Information including Medication Guide for IMFINZI.

You may report side effects related to AstraZeneca products.

References: 1. Paz-Ares L, Chen Y, Reinmuth N, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022;7(2):100408. 2. US Food & Drug Administration. FDA approves durvalumab for extensive-stage small cell lung cancer. Last updated March 30, 2020. Accessed October 2, 2023. ‌ht‌tp‌s:‌/‌/‌w‌w‌w.‌f‌d‌a.‌g‌ov‌/‌d‌r‌ug‌s‌/‌re‌so‌ur‌ce‌s‌-‌in‌fo‌rm‌a‌t‌i‌o‌n‌-‌a‌pp‌ro‌ve‌d‌-‌d‌r‌ug‌s‌/‌f‌d‌a‌-‌ap‌pr‌ov‌es‌-‌du‌rv‌al‌um‌ab‌-‌ex‌te‌ns‌iv‌e‌-‌st‌ag‌e‌-‌sm‌al‌l‌-‌ce‌ll‌-‌lu‌ng‌-‌ca‌nc‌er‌.‌ 3. Liu SV , Reck M, Mansfield AS, et al. Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133). J Clin Oncol. 2021;39(6):619-630. 4. IMFINZI^® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2023. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Small Cell Lung Cancer V.1.2024. ©National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed September 7, 2023. To view the most recent and complete version of the guideline, go online to ‌N‌C‌C‌N‌.‌o‌r‌g. 6. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum‑etoposide versus platinum-etoposide in first-line treatment of extensive-stage small‑cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939 (Including Supplementary Index).

This product information is intended for US Healthcare Professionals only.

IMFINZI is a registered trademark of the AstraZeneca group of companies.

This content is sponsored by AstraZeneca, and ION Oncology Practice Network has not independently reviewed or verified the information provided by AstraZeneca.

This email was sent to meghan.jacobson@amerisourcebergen.com because you have an account with or are a valued partner of Cencora Specialty GPOs | ION Oncology Practice Network. If you no longer wish to receive these types of emails, please click here to unsubscribe or update your email preferences.