India: US FDA Expands Approval Of Imfinzi To Reduce The Risk Of Non-Small Cell Lung Cancer Progression

On February 16, 2018, the United States Food and Drug Administration (US-FDA) approved Imfinzi (Durvalumab) for the treatment of patients with stage III non-small cell lung cancer (NSCLC) whose tumors cannot be surgically removed (unresectable) and whose cancer has not progressed after treatment with chemotherapy and radiation (chemoradiation)50. The FDA granted the approval of Imfinzi to AstraZeneca. The FDA has granted this application with Priority Review and Breakthrough Therapy designations.

This is the first treatment approved for stage III unresectable non-small cell lung cancer to reduce the risk of the cancer progression, when the cancer has not worsened after chemoradiation. For patients with stage III lung cancer that cannot be removed surgically, the current approach to prevent progression is chemoradiation. Although a small number of patients may be cured with the chemoradiation, the cancer may eventually progress. Patients now have an approved therapy that has been shown to keep the cancer from progressing for a longer time after chemoradiation.

Lung cancer is the leading cause of cancer deaths in the United States, with an estimated 222,500 new diagnoses and 155,870 deaths in 2017, according to the National Cancer Institute at the National Institutes of Health. The most common type of lung cancer, NSCLC occurs when cancer cells form in the tissues of the lung. Stage III NSCLC means tumors have spread to nearby lymph nodes or into other parts of the body near the lungs.

Imfinzi targets the PD-1/PD-L1 pathway (proteins found on the body's immune cells and some cancer cells). By blocking these interactions, Imfinzi may help the body's immune system attack cancer cells. Imfinzi was previously granted accelerated approval in 2017 for the treatment of certain patients with locally advanced or metastatic bladder cancer.

Imfinzi's current approval

The approval of Imfinzi for the treatment of stage III, unresectable NSCLC was based on a Phase III randomized trial (PACIFIC Trial) of 713 patients whose cancer had not progressed after completing chemotherapy and radiation51.713 patients were randomized in a 2:1 ratio, to receive durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) or placebo every 2 weeks for up to 12 months. The study drug was administered 1 to 42 days after the patients had received chemoradiotherapy.

The trial measured the length of time the tumors did not have significant growth after starting treatment with Imfinzi or a placebo (progression-free survival). The median progression-free survival (PFS) for patients taking Imfinzi was 16.8 months compared to 5.6 months for patients receiving a placebo. Therefore, Imfinzi demonstrated an improvement in median PFS of 11.2 months compared to placebo, representing a 48% reduction in relative risk of progression or death vs. placebo in all patients, regardless of PD-L1 status.

Overall, the incidence and severity of adverse events were comparable for patients receiving Imfinzi and the patients receiving placebo. In patients receiving Imfinzi, the most common adverse reactions (greater than or equal to 20% of patients) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnoea (25%), and rash (23%). Discontinuation after concurrent CRT due to adverse reactions, regardless of causality, occurred in 15% of patients receiving Imfinzi vs. 10% of patients receiving placebo.

About Stage III Non-Small Cell Lung Cancer

In this stage, tumors are more than 3 cm wide and are already spread to the lymph nodes in the center of the chest or other structures outside the lung. In stage III lung cancer, the affected lymph nodes are restricted to the same side of the body as the tumor. Stage III lung cancers are classified as either stage IIIA or IIIB, depending on the size and location of the tumor or how far it has spread. This differentiates it from Stage IV disease, when the cancer has spread (metastasised) to distant organs52.

About 30 percent of patients diagnosed with lung cancer are at stage III at the time of diagnosis. The five-year survival rate for stage IIIA lung cancer varies widely, and is about 23 percent on average. For stage IIIB lung cancer, the survival rate is about 10 percent. For many stage IIIA cancers and nearly all stage IIIB cancers, the tumor may be difficult and sometimes impossible to remove as most likely the the tumor may have spread outside the lung to lymph nodes located in the center of the chest. Or the cancer may have spread into structures near the lung. In either case, the thoracic surgeon may not able to remove all the cancerous cells and may recommend chemotherapy combined with radiation treatments prior to considering surgery.

About Imfinzi

Imfinzi (durvalumab), is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses. Durvalumab is a selective, high-affinity, human IgG1 monoclonal antibody that blocks programmed death ligand 1 (PD-L1) binding to programmed death 1 (PD-1) and CD80, allowing T cells to recognize and kill tumor cells53. Imfinzi has already received accelerated approval in the US for the treatment of patients with locallyadvanced or metastatic urothelial carcinoma, who have disease progression during or following platinumcontaining chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery.

Conclusion:

Imfinzi (durvalumab) is the first treatment to be approved for stage III unresectable non-small cell lung cancer to reduce the risk of the cancer progressing, when the cancer has not worsened after chemoradiation.

Footnotes

50. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm597217.htm

51. http://www.nejm.org/doi/full/10.1056/NEJMoa1709937

52. https://www.cancercenter.com/lung-cancer/stages/tab/non-small-cell-lung-cancer-stage-III/

53. http://www.nejm.org/doi/10.1056/NEJMoa1709937

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