EFFICACY

MONTHS MATTER IN ES-SCLC

Overall Survival

IMFINZI + EP: Sustained survival benefit at 2 years1*

Superior overall survival at interim analysis
(median duration of follow-up 14.2 months)2,3†

Consistent overall survival at updated analysis1,3
(median duration of follow-up 25.1 months)

Overall Survival in ES-SCLC with IMFINZI + EP and EP alone
  • At the time of the updated 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

*The hazard ratio was 0.73 at the interim analysis and 0.75 at the updated analysis.1,2

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).2,3

The updated OS analysis was conducted with a median duration of follow-up of 25.1 months. OS rates at 12, 18, and 24 months are the estimated proportion of patients alive based on the updated analysis.1.3

Months matter in ES-SCLC—Start with IMFINZI + EP for all eligible patients2

NCCNPREFERRED,CATEGORY 1

Durvalumab (IMFINZI®) + etoposide with either cisplatin or carboplatin is a Category 1, preferred treatment option for first-line ES-SCLC4§||

§Preferred intervention=intervention that is based on superior efficacy, safety, and evidence, and, when appropriate, affordability. Category 1=based upon high-level evidence, there is uniform National Comprehensive Cancer Network® (NCCN®) consensus that the intervention is appropriate. 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. To view the most recent and complete version of the guideline, go online to NCCN.org.

||See the NCCN Guidelines® for detailed recommendations, including other preferred treatment options.4

Overall survival with IMFINZI + EP remained consistent across all subgroups with >2 years of follow-up1

Prespecified subgroup overall survival analysis
(median duration of follow-up 25.1 months)1

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Interim analysis: overall survival demonstrated across patient subgroups with IMFINZI + EP
Interim analysis: overall survival demonstrated across patient subgroups with IMFINZI + EP

OS subgroup analysis was not powered to show a statistically significant difference between or within individual subgroups.3

IMFINZI + EP was evaluated in key patient subgroups reflective of clinical practice in ES-SCLC, including3,5-9:

  • Patients with brain/CNS metastases
  • Patients with liver metastases
  • Patients who received cisplatin or carboplatin
  • Patients over 65

ES-SCLC=extensive stage small cell lung cancer; EP=etoposide and either carboplatin or cisplatin; mOS=median overall survival; HR=hazard ratio; CI-confidence interval; OS=overall survival; ECOG=Eastern Cooperative Oncology Group; WHO=World Health Organization; PS=performance status; CNS=central nervous system; AJCC=American Joint Committee on Cancer.

 

Progression-Free Survival in ES-SCLC

Landmark progression-free survival data for IMFINZI + EP with >2 years of median follow-up1,3

Progression-free survival at updated analysis1
(median duration of follow-up 25.1 months)*

  • Median PFS at the interim analysis was 5.1 months (95% CI, 4.7-6.2) with IMFINZI + EP and 5.4 months (95% CI, 4.8-6.2) with EP alone (HR=0.78; 95% CI, 0.65-0.94; 96% of total planned events)2
    • Median PFS did not change at the updated analysis1
  • PFS was not formally tested for statistical significance at the interim or updated analysis1,3
  • PFS rate at 12 months was a secondary endpoint at the interim and updated analyses3

PFS=progression-free survival.

*PFS rates at 12, 18, and 24 months are the estimated proportion of patients alive and progression free based on the updated analysis.1

 

Objective Response Rate and Duration of Response in ES-SCLC

IMFINZI + EP provided a high response rate and demonstrated ongoing responses at 1 and 2 years1-3

Confirmed objective response rate (post-hoc analysis)2,3*

68% confirmed objective response rate in first-line ES-SCLC with IMFINZI + EP compared to 58% with only EP
  • Complete responses: 2% with IMFINZI + EP and 1% with EP alone3
  • Partial responses: 66% with IMFINZI + EP and 57% with EP alone3
Percentage of responders with ongoing responses (post-hoc analysis)1 (median duration of follow-up 25.1 months)

23% ongoing response rate at 12 months with IMFINZI + EP compared to 6% with only EP
  • Number of responders: 182 with IMFINZI + EP and 156 with EP alone1
  • Median duration of response: 5.1 months (95% CI, 4.9-5.3) with IMFINZI + EP and 5.1 months (95% CI, 4.8-5.3) for patients treated with EP alone10

RECIST=Response Evaluation Criteria in Solid Tumors.

*Investigator assessed per RECIST v1.1.

 

CASPIAN Study Design and Patient Characteristics

The Phase III CASPIAN study compared IMFINZI + EP vs EP and was designed to reflect real-world clinical practice3,6

A large, randomized, open-label, multicenter study of IMFINZI + etoposide and platinum-based chemotherapy (EP) vs EP alone2,3

Phase III CASPIAN study design

Primary endpoint2,3

Overall survival

Key secondary endpoints2,3

  • PFS§
  • ORR (unconfirmed)§
  • OS at 18 months
  • PFS at 6 and 12 months
  • HRQoL patient-reported outcomes
CASPIAN allowed for
Investigator’s choice of platinum-based chemotherapy

Investigator’s choice of platinum-based chemotherapy3||

Patients with asymptomatic or treated brain metastases

Patients with asymptomatic or treated brain metastases

The control arm allowed for
57% of patients to receive 6 cycles of EP

Up to 6 cycles of EP. 57% of patients received 6 cycles1,2

PCI per investigator’s discretion

PCI per investigator’s discretion2,3

No PD-L1 testing was required3

Baseline patient characteristics were well balanced between the IMFINZI + EP and EP arms3

Patients with asymptomatic or treated brain or CNS metastases were eligible to start systemic treatment.1

Patient characteristics3

IMFINZI + EP
(n=268)
EP alone
(n=269)
Median age (years) (range) 62 (58-68) 63 (57-68)
Gender
Male 71% 68%
Female 29% 32%
ECOG/WHO PS
0 37% 33%
1 63% 67%
Stage
III 10% 9%
IV 90% 91%
Smoking history
Current smoker/former smoker 92% 94%
Never smoker 8% 6%
Brain or CNS metastases 10% 10%
Liver metastases 40% 39%

Q3W=once every 3 weeks; Q4W=once every 4 weeks; PCI=prophylactic cranial irradiation; ORR=objective response rate; HRQoL=health-related quality of life; PD-L1=programmed death-ligand 1; AUC=area under the curve; CT=computed tomography; MRI=magnetic resonance imaging.

*IMFINZI 1500 mg + either carboplatin (AUC 5 mg/mL/min or 6 mg/mL/min) or cisplatin (75 mg/m2-80 mg/m2) on Day 1 and etoposide (80 mg/m2-100 mg/m2) intravenously on Days 1, 2, and 3 of each 21-day cycle for 4 cycles, followed by IMFINZI 1500 mg every 4 weeks until disease progression or unacceptable toxicity.2,3

Either carboplatin (AUC 5 mg/mL/min or 6 mg/mL/min) or cisplatin (75 mg/m2-80 mg/m2) on Day 1 and etoposide (80 mg/m2-100 mg/m2) intravenously on Days 1, 2, and 3 of each 21-day cycle for 4 to 6 cycles.2,3

8% of patients who were treated with EP alone received PCI post-EP.2,3

§Assessed using investigator assessments according to RECIST v1.1.3

||78% received carboplatin and 25% received cisplatin in the IMFINZI + EP arm; 78% received carboplatin and 25% received cisplatin in the EP alone arm.3

Patients with confirmed brain metastases had to be treated and stable off steroids and anticonvulsants for at least 1 month prior to study treatment. Patients with suspected brain metastases at screening should have a CT/MRI of the brain prior to study entry.3

 

Important Safety Information

There are no contraindications for IMFINZI® (durvalumab).

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).

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 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 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 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 2.0% (28/1414), 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 16.6% (79/475) in patients receiving IMFINZI and 13.2% (31/234) in patients receiving placebo. Of the 79 patients who received IMFINZI, 1.1% were fatal and 2.5% were Grade 3-4 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 when 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 1.6% (31/1889) of patients receiving IMFINZI, including Grade 4 (0.1%) and Grade 3 (0.3%) adverse reactions.

Immune-Mediated Hepatitis

IMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1.0% (19/1889) of patients receiving IMFINZI, including fatal (<0.1%) and Grade 3 (0.6%) 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 0.4% (7/1889) 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 0.4% (7/1889) of patients receiving IMFINZI.
  • Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 1.4% (27/1889) of patients receiving IMFINZI.
  • Hypothyroidism: Immune-mediated hypothyroidism occurred in 7.3% (137/1889) 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 0.3% (5/1889) 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), have 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 1.6% (30/1889) 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 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. Advise females of reproductive potential to use effective contraception during treatment with IMFINZI and for at least 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 at least 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, fatigue/asthenia, and alopecia. 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.

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).

Please see complete Prescribing Information, including Medication Guide.

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