- AstraZeneca plc's Imfinzi won approval to treat unresectable stage 3 patients with non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemo- and radiation therapy, in part based on positive results from its PACIFIC trial.
- Imfinzi is the first therapy approved by the Food and Drug Administration for such patients, who previously received active surveillance. The drug will be available immediately for the new indication.
- In the PACIFIC trial, patients taking Imfinzi had a median progression-free survival of 16.8 months compared with 5.6 months on placebo, an 11.2 month improvement. This trial is ongoing, and will look at overall survival (OS) in unresectable stage 3 NSCLC.
After a dramatic failure of the MYSTIC trial in 2017 made it a tough year for AstraZeneca's Imfinzi (durvalumab), the approval is a major step forward in the hard-fought lung cancer field. In PACIFIC, Imfinzi reduced the risk of disease progression by almost half in unresectable stage 3 NSCLC patients, and was the first immuno-oncology therapeutic to show a benefit for this subgroup of patients.
"This approval is the first in non-small cell lung cancer for Imfinzi, and the first approval in the U.S. for any drug for these patients, who otherwise have no option," said Olivier Nataf, VP for U.S. oncology at the British pharma, in an interview with BioPharma Dive.
"Until now, treatment guidelines have recommended that patients with unresectable stage 3 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… The PACIFIC trial data supporting today’s approval of Imfinzi will change how we treat these patients," Scott Antonia of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida and investigator in the PACIFIC trial, said.
Imfinzi is now included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for its new indication.
The MYSTIC results were a challenge for the company. In late July the PD-L1 inhibitor, in combination with the AstraZeneca's CTLA4 inhibitor tremelimumab, failed to show a progression-free survival benefit in first-line treatment of metastatic NSCLC. While the company hasn't given up hope, and is still waiting on overall survival data, at the time the news took the company's share value down 15% within hours.
The PACIFIC studies have gone some way to redeem MYSTIC's failure, and the approval puts AstraZeneca ahead of its competitors for unresectable stage 3 disease, which affects around 15,000 patients per year in the U.S. However, the locally-advanced market is a less lucrative one than metastatic disease, where Bristol-Myers Squibb Company and Merck & Co. currently have the advantage.
"While there are more patients in the first-line metastatic indication, we are the only medication available for stage 3 unresectable disease, which means we are in a different competitive landscape," said Nataf. "There is no better example than PACIFIC to show our approach in NSCLC. We are targeting earlier stage disease with a curative intent, and looking for options for longer and better outcomes for our patients."
In immuno-oncology in lung cancer, Merck & Co. and Bristol-Myers Squibb have it pretty well locked down, with Merck's Keytruda (pembrolizumab) and Bristol-Myers' Opdivo (nivolumab). Keytruda is the only checkpoint inhibitor approved in first-line as a monotherapy or combination, and lung cancer sales are fueling its position in the market. Keytruda has also shown positive results as part of a combination in non-squamous NSCLC.
Other NSCLC checkpoint inhibitor data readouts in NSCLC are expected in 2018, which may shake up Keytruda and Opdivo's hold on the market. These include Roche AG's overall survival results from its IMPower150 study of the combination of Tecentriq (atezolizumab), Avastin (bevacizumab) and chemotherapy in first-line NSCLC.
Regeneron Pharmaceuticals Inc. and Sanofi SA are enrolling patients in a Phase 3 trial in frontline NSCLC for their PD-1 inhibitor cemiplimab as monotherapy, with combination studies planned. Pfizer Inc. and Merck KGaA are also working on NSCLC with their PD-L1 inhibitor Bavencio (avelumab), though this has stumbled somewhat in a Phase 3 trial, JAVELIN Lung 200.