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ATLANTIC Points To Durvalumab Potential For Heavily Pretreated NSCLC

The immune checkpoint inhibitor durvalumab has shown varying efficacy in patients with advanced non-small-cell lung cancer and a range of different biomarkers
15 Mar 2018
Immunotherapy;  Non-Small Cell Lung Cancer;  Translational Research;  Basic Principles in the Management and Treatment (of cancer);  Therapy
By Lynda Williams, Senior medwireNews Reporter

medwireNews: The programmed cell death ligand 1 (PD-L1) inhibitor durvalumab may have efficacy for patients with heavily pretreated, advanced non-small-cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangement, ATLANTIC investigators say.

The phase II trial conducted in Asia, Europe and North America recruited NSCLC patients with disease progression after at least two lines of systemic treatment including platinum-based chemotherapy and, where indicated, tyrosine kinase inhibitor agents, but no prior exposure to PD-L1  or programmed cell death protein 1 (PD-1) inhibitors.

Marina Chiara Garassino, from Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, and co-workers report pneumonitis (1%), elevated gamma-glutamyltransferase (1%), diarrhoea (1%), and infusion-related reactions (1%) as the most common treatment-related grade 3 or 4 events in the patients given durvalumab 10 mg/kg every 2 weeks for up to 12 months.

The most common serious side effects were pneumonitis, fatigue and infusion-related reactions, affecting 1% of patients each, although the researchers describe the immune-mediated events as being “manageable with standard treatment guidelines.”

The 444 participants were divided into three cohorts depending on their EGFR and ALK rearrangement status, and the proportion of their tumour cells expressing PD-L1.

Among patients with at least 25% of tumour cells expressing PD-L1, an objective response was achieved by 12.2% of the 74 patients positive for EGFR or ALK aberrations and 16.4% of the 146 patients negative for both biomarkers. The corresponding rates for patients in these groups with PD-L1 expression on less than 25% of tumour cells were 3.6% and 7.5%. 

However, the objective response rate rose to 30.9% for the 68 patients who were EGFR-negative/ALK-negative and had at least 90% of tumour cells positive for PD-L1. 

Among patients with EGFR-negative/ALK-negative tumours, median progression-free survival was longer for patients meeting the 25% and 90% thresholds for PD-L1 expression than for those with lower levels of expression, although this was not true for patients positive for EGFR or ALK. Moreover, median overall survival was better in patients with at least 25% and 90% PD-L1 expression regardless of EGFR and ALK status, the researchers point out.

Noting that most of the EGFR-positive or ALK-positive patients who responded to durvalumab had EGFR mutations and PD-L1 expression over 25%, the ATLANTIC investigators suggest that “durvalumab might have a role in the treatment of EGFR+ tumours with high PD-L1 expression.”

They believe: “Additional prospectively designed controlled studies in patients with EGFR+/ALK+ NSCLC are warranted to further understand the activity of immune checkpoint inhibitors in this population.”

The authors of a linked comment agree that the data for EGFR-positive and ALK-positive patients suggests these groups may have “distinct immunobiologies”.

Jessica Lin and Justin Gainor, from Massachusetts General Hospital in Boston, USA, write: “This finding underscores that PD-L1 expression alone is imperfect and will probably need to be complemented by other factors, such as clinical characteristics (eg, smoking), immune cell density, and tumour mutation burden.”

While acknowledging that EGFR and ALK targeted therapies remain the “cornerstones of therapy” for tumours with these biomarkers, the commentators recommend that “clinicians should consider directing patients with EGFR+/ALK+ NSCLC to clinical trials evaluating immunotherapy combinations.”

They add: “Such efforts might create a potential space for immune-based treatment approaches in these molecular subgroups—thus far a largely uncharted territory.”

References

Garassino MC, Cho B-C, Kim J-H, et al. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study.Lancet Oncol; Advance online publication 12 March 2018.

DOI: https://doi.org/10.1016/S1470-2045(18)30144-X

Lin JJ, Gainor JF. ATLANTIC: a sea change in immunotherapy for oncogene-driven lung cancer? Lancet Oncol; Advance online publication 12 March 2018.
DOI: https://doi.org/10.1016/S1470-2045(18)30160-8

Last update: 15 Mar 2018

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

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