The US Food and Drug Administration (FDA) has approved the checkpoint inhibitor immunotherapy drug Imfinzi (durvalumab) for the treatment of patients with non-small cell lung cancer (NSCLC) in several settings because it reduces the risk of cancer recurrence and prolongs survival.2,3
About Non-Small Cell Lung Cancer
Lung cancer is the most common cancer in the world and is the leading cause of cancer death, with 160,000 deaths in the U.S. annually. There are two main kinds of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), which together account for over 90% of all lung cancers. Malignant mesothelioma is a rare cancer that develops in the tissues that comprise the lining of the lung. Non-small cell lung cancer accounts for approximately 75% of these cancers and consists of squamous cell, adenocarcinoma, and large cell types. Small cell lung cancer represents 20-25% of all lung cancers and is also referred to as “oat cell cancer” Non-small cell lung cancer can be subdivided into numerous different cancers based on the genetic mutation causing the cancer.
Most cancers result from abnormal genes or gene regulation. By identifying these genomic changes and knowing which genes are altered in a patient, with NSCLC cancer drugs that specifically attack that gene (or the later consequences of that gene) can be used to target the cancer and avoid the more general side effects of chemotherapy. All newly diagnosed lung cancer patients should undergo multi-gene and biomarker testing as part of their initial evaluation. Research suggests testing on blood and tissue is superior to using either alone and earlier blood-based testing results in faster treatment and improved outcomes.
Doctors identify cancer growth driving mutations by performing “next generation sequencing” (NGS) on the biopsy that identified the lung cancer and in the blood. Identifying the specific genomic alteration rather than relying on a simple broad classification of cancer solely based on its site of origin avoids the traditional “one-size-fits-all” approach to cancer treatment and allows for the identification of a precision cancer medicine or immunotherapy to treat a specific cancer.
About Imfinzi (durvalamab)
Imfinzi is a human monoclonal antibody directed against programmed death ligand-1 (PD-L1). PD-L1 can be expressed by cancer cells, and it helps them evade detection by the immune system through binding to PD-1 on cytotoxic T lymphocytes. Imfinzi blocks the PD-L1 interaction with PD-1, countering the cancer’s immune-evading tactics. Imfinzi empowers the patient’s immune system to attack the cancer.
Early Stage NSCLC – The AEGEAN Clinical Trial
The addition of peri-operative Imfinzi to neoadjuvant chemotherapy improves pathological complete response (pCR) rates and prolongs cancer free survival in patients with stage II to IIIB NSCLC, according to findings from the phase 3 AEGEAN clinical trial.
Previous clinical studies have demonstrated that combining chemotherapy with immune checkpoint inhibitor drugs prolong survivals when used as adjuvant or neoadjuvant therapy for early stage IB-IIIB NSCLC. The results of the AGEAN clinical trial suggest that combining neoadjuvant (before surgery) and adjuvant (post-surgery) immunotherapy with chemotherapy may be the best strategy to reduce the risk of cancer recurrence and prolong survival.5
The AEGEAN clinical trial directly compared a treatment strategy of neoadjuvant Imfinzi + platinum-based chemotherapy and post-surgical Imfinzi maintenance to treatment with neoadjuvant chemotherapy alone in 802 patients. The initial trial results were released at the September 2023 World Lung Meetings.
- Imfinzi improved the pCR rate from 4.3% to 17.2% leading to a modest improvement in surgical resection rates.
- The 24-month survival rates without cancer progression were improved from 52% to 63% with the addition of Imfinzi.
- Overall survival rates are not yet reported.
Stage III NSCLC – The PACIFIC Clinical Trial
The PACIFIC clinical evaluated the use of Imfinzi as sequential treatment in patients with locally advanced, unresectable, stage III NSCLC following treatment with chemotherapy and radiation. All patients were treated with 2 cycles of platinum-based chemotherapy and radiation with the goal of making the cancer more sensitive to treatment with immunotherapy.
Patients then received treatment with either a placebo or sequential Imfinzi for up to 12 months if they had not progressed following standard platinum-based chemotherapy concurrent with radiation.2,3
Imfinzi was initially reported to significantly delay the time to cancer progression compared with placebo. Imfinzi treated patients survived on average 17 months without cancer progression compared to only 6 months for those treated with placebo. Trial results were updated in 2022.4 Overall 50% of Imfinzi treated patients survived 4 years from treatment compared to 36% of those treated with chemoradiation without Imfinzi. The median survival duration was 48 months for Imfinzi versus 29 months for placebo. With a maximum treatment course of one year, an estimated 35.3% of patients treated with Imfinzi had not progressed four years after enrollment versus 19.5% for placebo.
The survival benefit for patients with unresectable stage III NSCLC harboring EGFR or ALK mutations with Imfinzi is unclear and further studies with target therapy is currently undergoing for this subgroup of patients.
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References
- Kantar, other market research based on 2016 patient numbers; Globocan 2012. G7 countries include the US, Japan, Germany, the UK, France, Italy and Canada.
- AstraZeneca news release. (2016.) Retrieved from: Durvalumab granted Breakthrough Therapy designation by US FDA for treatment of patients with PD-L1 positive urothelial bladder cance
- Imfinzi significantly improves overall survival in the Phase III PACIFIC trial for unresectable Stage III non-small cell lung cancer Antonia. N Engl J Med. 2018;379:2342
- Spigel et al, J Clin Oncol. 2022 Feb 2:JCO2101308. doi: 10.1200/JCO.21.01308
- Mitsudomi T, Heymach JV, Reck et al. Surgical outcomes with neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in resectable NSCLC (AEGEAN). Presented at: International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer; September 9-12, 2023; Singapore. Abstract OA12.05.
