A Tsunami of Benefit from PACIFIC
From an “Earthquake of Immunotherapy in NSCLC”, the title of a session that followed the Presidential Symposium at ESMO 2016, to a “tsunami of benefit” at ESMO 2017; this is how Prof. Johan Vansteenkiste, discussant of the eagerly awaited PACIFIC trial, summed up the interim PACIFIC data. But what kind of tsunami is this?
When used as a 12-month consolidation treatment in locally advanced (stage III), unresectable NSCLC patients whose disease had not progressed following standard or care with platinum-based concurrent chemoradiotherapy (cCRT), Imfinzi achieved a significant and robust PFS benefit of 11 months over placebo (16.8 vs. 5.6 months, respectively); a 48% reduction in the risk of progression. PFS was supported by clinically meaningful ORR and durable responses. No new safety signals were observed.
These are the first positive Phase III data for an immune checkpoint inhibitor in stage III NSCLC, putting AstraZeneca in pole position ahead of same-in-class rivals. The unmet clinical need for stage III NSCLC is indisputable: median PFS with cCRT is just 8-10 months, five-year survival is 15%, and according to Decision Resources Group’s proprietary epidemiology, more than one quarter of diagnosed NSCLC patients have stage III disease. Capitalizing on stage III NSCLC (and getting a head start in this population) could therefore yield significant commercial gains for Imfinzi.
- What is the OS benefit? While interim PFS is strong and prolonged, time to distant metastases with Imfinzi is • What is the OS benefit? While interim PFS is strong and prolonged, time to distant metastases with Imfinzi is a good indicator of benefit in stage III disease, OS (coprimary end point) data are immature. Hailing Imfinzi as practice changing may be premature until we know the OS benefit, but it is looking hopeful.•
- Is the commercial opportunity limited? Not all stage III patients receive cCRT (a sizeable proportion receives sequential chemotherapy and radiotherapy) and of those receiving cCRT not all will respond (patients who progressed on cCRT were excluded from PACIFIC). •
- Could patients benefit if treated with an immune checkpoint inhibitor prior to cCRT? While PACIFIC was not designed to test this (and neither is the ongoing Phase III Opdivo trial in stage III NSCLC) this speculative question may warrant investigation in future studies.
The positive data unveiled from PACIFIC fuels renewed optimism for Imfinzi in NSCLC after a series of setbacks. Not least, the PACIFIC data softens the blow of MYSTIC (Imfinzi plus tremelimumab in previously untreated metastatic NSCLC), which recently failed to meet co-primary end point (PFS). All eyes are now on MYSTIC’s OS data (expected in 2018). But don’t count it out! PD-1 and CTLA-4 combination Opdivo plus Yervoy has hit the headlines at ESMO 2017 by showing OS benefit in previously untreated advanced or metastatic renal cell carcinoma, after failing to show a PFS benefit just a few weeks ago (CheckMate-214).
For Decision Resources Group’s 10-year market forecast of Imfinzi in commercially important patient populations, including stage III NSCLC, see the NSCLC Disease Landscape & Forecast. Our new monthly updated Real World Brand Tracker service uses real world claims data to help you quickly understand the competitive environment among ICIs across oncology indications in this highly dynamic market segment. For more insights on oncology drug development, follow @RWebsterDRG
- Paz-Ares L, et al. PACIFIC: A double-blind, placebo-controlled Phase III study of durvalumab after chemoradiation therapy (CRT) in patients with Stage III, locally advanced, unresectable NSCLC. ESMO. 2017. LBA1_PR
- Antonia SJ, et al. Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. NEJM. Published online September 8, 2017.
- Decision Resources Group proprietary epidemiology analysis. The seven major markets include the United States, France, Germany, Italy, Spain, the United Kingdom, and Japan.