AstraZeneca and MedImmune, its global biologics research and development arm, announced that the US Food and Drug Administration (FDA) has approved Imfinzi for the treatment of patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (CRT).

Dave Fredrickson, executive vice president, head of the oncology business unit at AstraZeneca, said: “The approval of Imfinzi in this earlier stage of non-small cell lung cancer is a truly meaningful milestone for patients who, until now, had no FDA-approved treatment options following chemoradiation therapy. Globally, approximately 30% of patients with NSCLC present with Stage III disease and we are excited to launch the first immunotherapy into this setting.”

Scott J. Antonia, MD, Ph.D., Chair of the Thoracic Oncology Department at the H. Lee Moffitt Cancer Center and Research Institute in Tampa and investigator in the PACIFIC trial, said: “Until now, treatment guidelines have recommended that patients with unresectable Stage III lung cancer undergo a period of active surveillance following chemoradiation therapy until disease progression. Given that up to 89% of patients will progress to metastatic disease, it is important that there is now a new option that can give patients more time without disease progression. The PACIFIC trial data supporting today’s approval of Imfinzi will change how we treat these patients.”

The approval of Imfinzi is based on the positive PFS data from the phase III PACIFIC trial in which 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. The PACIFIC trial is ongoing to evaluate overall survival (OS) in unresectable Stage III NSCLC. Detailed interim results of the PACIFIC trial were published online in the New England Journal of Medicine (NEJM).

Imfinzi: Blinded Independent Central Review (BICR);  Among the ITT population, 7% in the IMFINZI arm and 10% in the placebo arm had non-measurable disease as assessed by BICR according to RECIST v1.1; Stratified by sex, age, and smoking history; Pike estimator; Compared with allocated a of 0.0104 (Lan DeMets spending function approximating O’Brien Fleming boundary) for interim analysis.

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.

On 28 September 2017, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology were updated to include Imfinzi for the treatment of patients with unresectable Stage III NSCLC with no disease progression after two or more cycles of concurrent CRT.

Stage III (locally advanced) NSCLC is commonly divided into three sub-categories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally and the possibility of surgery. This differentiates it from Stage IV disease, when the cancer has spread (metastasised) to distant organs.

Stage III NSCLC represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in France, Germany, Italy, Japan, Spain, the UK and the US in 2016. The majority of Stage III NSCLC patients are diagnosed with unresectable tumours. Until now, the current standard of care has been chemotherapy and radiation therapy, followed by active surveillance to monitor for progression. The prognosis remains poor and long-term survival rates are low.

Imfinzi (durvalumab), 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.

Imfinzi has already received accelerated approval in the US for the treatment of patients with locally-advanced or metastatic urothelial carcinoma, who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery.

As part of a broad development programme, Imfinzi is also being investigated for the adjuvant treatment of patients with NSCLC in the Canadian Cancer Trials Group BR31 trial (ADJUVANT). In the MYSTIC, NEPTUNE and PEARL Phase III trials, Imfinzi is being studied for 1st-line treatment as monotherapy and/or in combination with tremelimumab, an anti-CTLA-4 monoclonal antibody and potential new medicine, for the treatment of metastatic NSCLC. The POSEIDON trial is investigating Imfinzi with and without tremelimumab in combination with chemotherapy in a similar patient population.