ASCO Salt Lake City:Dr Gumbleton Discusses Results from ADRIATIC Trial

Presented by:

Matthew Gumbleton, MD, PhD, University of Utah/Huntsman Cancer Institute

Meeting:

Total Health ASCO Direct™ Salt Lake City

 The Bottom Line

Treatment for patients with limited stage small cell lung cancer consists of concurrent chemoradiotherapy, and has been largely unchanged for decades.  Results from the ADRIATIC trial now show that the addition of durvalumab immunotherapy in addition to concurrent chemoradiotherapy can improve progression free and overall survival relative to placebo.

Background:

Unlike the more commonly occurring non-small cell lung cancers (NSCLC) many of which are now amenable to treatment with immunotherapy and targeted therapy, new treatments for small cell lung cancers (SCLC) have lagged behind.  SCLC has been broadly grouped into patients with limited stage (LS) or extensive stage (ES) disease, and the use of curative intent, concurrent chemoradiotherapy (cCRT) has been the standard of care for patients with LS-SCLC for several decades.  Unfortunately, the vast majority of patients with LS-SCLC will ultimately relapse and succumb to their disease.  The ADRIATIC trial was designed to investigate the efficacy of 2 different kinds of immunotherapy as a consolidation treatment for patients with LS-SCLC who did not have a progression after their initial cCRT.

Trial Design and Patients:

This first analysis from the trial examined the efficacy of durvalumab (an anti-PD-L1 type immunotherapy) versus placebo.  Patients in the trial (n=264 durvalumab, n=266 placebo) were relatively fit, with a performance status of 0 or 1, and had stage I to III LS-SCLC and no progression after cCRT.  The patients were treated for a maximum of 2 years (24 months), and primary endpoints in the trial were overall survival (OS) and progression-free survival (PFS). 

Main Trial Results:

Overall, Dr Gumbleton thought the data were “quite striking”.  The median PFS (mPFS) was 16.6 months with durvalumab versus 9.2 months with placebo, and the difference was statistically significant (P=0.0161).  The mOS was also significantly longer with durvalumab versus placebo (55.9 vs. 33.4 months; P=0.0104), an increase of nearly 2 years, which Dr Gumbleton considered “a remarkable advancement”.  The benefits in PFS and OS were generally observed across all subgroups of patients (e.g. regardless of age, sex, race, and prior treatments).  There was also some suggestion in the trial that starting patients on durvalumab sooner was beneficial, rather than starting later.

Adverse Events and Toxicities:

The most commonly occurring adverse events were inflammation of the lung (pneumonitis) or radiation pneumonitis, which occurred in 38.2% and 30.2% of patients in the durvalumab and placebo groups, respectively.  These events were serious (grade 3 or 4) in 3.1% and 2.6% of patients in the respective groups.  Generally however, the toxicity profile was acceptable and consistent with the known safety profile of durvalumab and for LS-SCLC patients in the post cCRT setting.

Conclusions and Faculty Insights:

The authors concluded that durvalumab as a consolidation treatment after cCRT was associated with both statistically and clinically significant improvement in both PFS and OS over placebo for patients with LS-SCLC.  The authors further concluded that durvalumab consolidation will become the new standard of care for patients with LS-SCLC who have not had a progression after cCRT, an assertion which Dr Gumbleton was in full agreement with.

Speaker Disclosure Information:

Dr Gumbleton reported the following disclosures, outside of the scope of this presentation: Patents licensed to Alterna Therapeutics; Lab funding through the Lung Cancer Research Foundation; Honoraria from MJH Lifesciences; Honoraria from OMNI Health Media.