Rx Road Map: Durvalumab for Non-Small Cell Lung Cancer

Durvalumab's approvals were based on the AEGAN, PACIFIC, and POSEIDON trials.

Who Is This Drug Approved for?

Durvalumab (Imfinzi) is a PD-L1–blocking antibody that has 3 indications for non–small cell lung cancer (NSCLC).

All Approved Indications and Timeline

February 2018: Received approval for treatment of patients with stage III unresectable NSCLC following platinum-based chemotherapy and radiation whose disease has not progressed.¹

November 2022: Granted approval in combination with tremelimumab plus platinum-based chemotherapy for stage IV metastatic NSCLC (mNSCLC).²

August 2024: Approved by the FDA in the adjuvant/neoadjuvant setting for resectable, early-stage (IIA-IIIB) NSCLC in combination with neoadjuvant platinum-based chemotherapy before adjuvant monotherapy following surgery.³

What Efficacy Data Supported the Approval?

PACIFIC trial (NCT02125461): Patients with stage III unresectable NSCLC who completed at least 2 cycles of concurrent platinum-based chemotherapy with radiation were enrolled in the randomized, double-blind, placebo-controlled, multicenter study.¹

Results: Median progression-free survival (PFS) was significantly improved at 16.8 months in the durvalumab arm compared with 5.6 months in the placebo arm (HR, 0.52; 95% CI, 0.42-0.65; P = .00010).

POSEIDON trial (NCT03164616): Patients with EGFR/ALK wild-type metastatic NSCLC were randomly assigned to 3 treatment arms: durvalumab plus tremelimumab (Imjudo) with platinum-based chemotherapy for up to four 21-day cycles followed by durvalumab every 4 weeks until progression and 1 additional tremelimumab dose, durvalumab plus chemotherapy for up to four 21-day cycles followed by durvalumab every 4 weeks until progression, or chemotherapy for up to six 21-day cycles (with or without maintenance pemetrexed; all arms).² The primary end point was progression-free survival (PFS).

Results: PFS significantly improved with durvalumab plus tremelimumab and chemotherapy (6.2 months) vs the platinum-based chemotherapy arm (4.8 months). However, overall survival was significantly improved in the durvalumab plus tremelimumab and chemotherapy arm (14 months; 95% CI, 11.7-16.1) vs platinum-based chemotherapy (11.7 months; 95% CI, 10.5-13.1).

AEGEAN trial (NCT03800134): Patients with early-stage (IIA-IIIB) NSCLC were randomly assigned to treatment with platinum-based chemotherapy plus durvalumab or placebo every 3 weeks for up to 4 cycles prior to surgery followed by adjuvant durvalumab or placebo every 4 weeks for 12 cycles.³ The primary end points were event-free survival (EFS) and pathologic complete response (pCR).

Results: Median EFS was not reached (95% CI, 31.9-not estimable [NE]) in the durvalumab arm vs 25.9 months (95% CI, 18.9-NE) in the placebo arm (HR, 0.68; 95% CI, 0.53-0.88; P = .0039). pCR in the durvalumab arm was 17% (95% CI, 13%-21%) vs 4.3% (95% CI, 2.5%-7%) in the placebo arm.

How It Works

Durvalumab is in a class of drugs called checkpoint inhibitors, which attach to proteins on cancer cells, blocking their effects and allowing the body’s immune system to go in and attack the cancer. Specifically, durvalumab is a PD-L1 inhibitor, which blocks the PD-L1 protein from stopping immune activity.

Recommended Dose and Duration of Therapy

For stage III NSCLC following chemotherapy/radiation, 10 mg/kg of durvalumab is recommended every 2 weeks.¹

For patients with mNSCLC with a weight of more than 30 kg, the FDA recommends 1500 mg concurrently with chemotherapy on day 1 of each cycle for 4 cycles along with 75 mg of tremelimumab every 3 weeks and then every 4 weeks until progression, with a fifth dose of tremelimumab given at week 16.² For patients with a weight of 30 kg or less, the recommended doses of durvalumab and tremelimumab are 20 mg/kg and 1 mg/kg, respectively.

For patients with stage IIA to IIIB disease taking durvalumab concurrently with chemotherapy and a weight of 30 kg or more, the recommended dose is 1500 mg every 3 weeks in the neoadjuvant setting on day 1 of each chemotherapy cycle and then every 4 weeks in the adjuvant setting.³ Likewise, for patients with a weight less than 30 kg, the recommended dose is 20 mg/kg.

Adverse Event Information

Understanding Common Terminology Criteria for Adverse Events grading and critical thinking/assessment skills is important when monitoring patients on immunotherapy.

Pneumonitis: Monitor for shortness of breath, respiratory rate, and oxygen saturation. Radiographic imaging is needed for confirmation of pneumonitis. Grade 2 or higher pneumonitis will require corticosteroids and potential dose interruptions/discontinuation.⁵

Hepatitis: Monitor liver functions (aspartate aminotransferase, alanine aminotransferase, bilirubin) and patient’s skin/sclera for jaundice. Grade 2 or higher hepatitis will require corticosteroids and potential dose interruptions/discontinuation.

Colitis: Monitor severity of diarrhea (how many episodes, associated abdominal pain or blood) in addition to electrolyte levels. Patients may require hydration with electrolyte replacement. Grade 2 or higher colitis will require corticosteroids and potential dose interruptions/discontinuation.

Thyroid disorders: Assess for excess fatigue, weight gain, palpitations, excessive sweating, and unintentional weight loss. Monitor thyroid levels and treat with hormone replacement therapy for hypothyroidism or medical management of hyperthyroidism as needed.

Adrenal insufficiency: Monitor nonspecific symptoms such as fatigue, weight loss, and aches and pains. Monitor cortisol laboratory values. Grade 2 or higher adrenal insufficiency will require corticosteroids and potential dose interruptions/discontinuation.

Type 1 diabetes mellitus: Monitor for symptoms of hyperglycemia such as excessive thirst and urination. Monitor glucose and chemistry, initiate insulin treatment as clinically indicated, and interrupt durvalumab based on severity.

Hypophysitis: Monitor for headache and vision problems. Cortisol, thyroid-stimulating hormone, and luteinizing hormone laboratory values along with MRI can confirm diagnosis. Grade 2 or higher hypophysitis will require corticosteroids and potential dose interruptions/discontinuation.

Nephritis: Monitor patient for edema/fluid retention, hypertension, and headaches. Monitor renal function. Grade 2 or higher nephritis will require corticosteroids and potential dose interruptions/discontinuation.

Dermatologic reactions: Monitor for signs and symptoms of rash. If grade 1, initiate topical antihistamine/cortisone cream. Initiate oral corticosteroids 1 to 2 mg/kg per day for grade 2, lasting more than a week for severe reactions (grade 3-4), followed by taper. Nurses may need to interrupt or discontinue depending on severity.

Infection: Monitor patients for signs/symptoms of infection and hold durvalumab for grade 3 or higher.

Infusion-related reactions: Monitor for signs/symptoms of infusion reactions, including flushed face, back pain, shortness of breath, hives, rigors, and anaphylaxis. If reaction is mild, stop or slow infusion. If reaction is moderate or severe, initiate infusion reaction protocols. Treatment with durvalumab may need to be discontinued permanently. Nurses may consider premedication for subsequent durvalumab infusions.

Embryo-fetal toxicity: Advise women of reproductive potential to use effective birth control methods during treatment and for at least 3 months after receiving last dose of durvalumab.

What Do Patients Need to Know Before Starting Treatment?

Discuss immune-mediated adverse events (AEs) in detail, advising when to contact providers, particularly if they develop a cough, diarrhea, headache, or skin rash. Provide patients with a wallet card showing that they are being treated with immunotherapy and inform them of the importance of showing this to any health care provider treating them outside of their oncologist.

Discuss with the patient that if they feel any discomfort or difference during the infusion, they must notify the nurse immediately. If the patient is female and able to become pregnant, they will need to be on an effective form of birth control during treatment with durvalumab and for at least 3 months after completion of durvalumab.

Administration Information for Infusion Nurses and Clinical Nurse Specialists

• Durvalumab requires 0.22-μm filtered tubing.
• Durvalumab is given intravenously over 60 minutes, no matter the indication.
• Administration occurs every 2 or 4 weeks, depending on the indication.
• In combination with tremelimumab, durvalumab is administered after tremelimumab.

Nursing Considerations

Nurses should educate patients on infection prevention, such as staying away from anyone who is ill and avoiding large crowds unless wearing a mask. Patients should be advised to wash hands regularly and keep hand sanitizer nearby.

Discuss good skin care routines with patients, including using mild detergents, sunscreen, and lotions/soaps without heavy perfumes. Patients should be informed to contact their care team if a rash develops.

Patients should be given a nutritional consultation if they have issues with weight loss/gain related to AEs. Discuss the importance of calorie and protein intake as well as foods to avoid if diarrhea is present. Potential home oxygen/durable medical equipment needs of a patient may need to be considered with pneumonitis diagnosis.

How to Safely Handle This Drug

Although durvalumab is not considered a hazardous drug by National Institute for Occupational Safety and Health standards, it is recommended that nurses wear proper personal protective equipment when administering this drug and that proper infection protocols are used when preparing and administering durvalumab.

References

1. FDA approves durvalumab after chemoradiation for unresectable stage III NSCLC. FDA. February 16, 2018. Accessed April 23, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-after-chemoradiation-unresectable-stage-iii-nsclc
2. FDA approves tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic non-small cell lung cancer. FDA. November 18, 2022. Accessed April 23, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-and-platinum-based-chemotherapy-metastatic-non
3. FDA approves neoadjuvant/adjuvant durvalumab for resectable non-small cell lung cancer. FDA. August 15, 2024. Accessed April 23, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-durvalumab-resectable-non-small-cell-lung-cancer
4. IMFINZI (durvalumab) immunotherapy for cancer. Imfinzi. 2025. Accessed April 23, 2025. https://www.imfinzihcp.com/
5. Imfinzi. Medication guide. AstraZeneca; 2025. Accessed April 23, 2025. https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/9496217c-08b3-432b-ab4f-538d795820bd/9496217c-08b3-432b-ab4f-538d795820bd_pi_med_guide_rendition__c.pdf