LUNG CANCER

When findings of larotrectinib, a pan-TRK inhibitor co-developed by Bayer and Loxo Oncology, that generated significant excitement for the treatment of both adult and pediatric patients with TRK fusion cancers, were presented during the 2017 ASCO Annual Meeting, the small molecule was lauded as a future standard of care for patients with advanced solid tumors harboring a TRK fusion.

This article provides a short historical overview of major lung cancer vaccination studies performed in the last decade to set the perspective on the development of current clinical trials of therapeutic cancer vaccines for patients with non–small cell lung cancer. 

According to results from an ongoing trial presented at the 2018 AACR Annual Meeting, adding atezolizumab to chemotherapy and an angiogenesis inhibitor led to significant improvement in progression-free survival for patients with untreated advanced nonsquamous non–small cell lung cancer.

Based on data from the phase I/II CheckMate-032 trial, nivolumab has been granted a priority review by the FDA for the treatment of patients with small cell lung cancer with disease progression following 2 or more lines of therapy, according to Bristol-Myers Squibb, the manufacturer of the PD-1 inhibitor.

Osimertinib (Tagrisso) has been approved by the FDA as a frontline treatment for patients with non-small cell lung cancer who have tumors harboring EGFR mutations (either exon 19 deletions or exon 21 L858R substitution mutations). This approval is based off results from a recent phase III study.

Benjamin J. Drapkin, MD, PhD, clinical fellow in medicine, Dana-Farber Cancer Institute, resident, Massachusetts General Hospital, discusses the co-clinical trial of olaparib (Lynparza) and temozolomide (temodar) in small cell lung cancer (SCLC) patient-derived xenografts (PDX) models during the 2018 AACR Annual Meeting.

In an updated analysis of CheckMate-586, investigators found that tumor mutational burden identified patients with non–small cell lung cancer who were more likely to respond to first-line combination immunotherapy with nivolumab and ipilimumab.

The 1-year progression-free survival rate was more than tripled with the combination of nivolumab and ipilimumab versus chemotherapy in treatment-naïve patients with non–small cell lung cancer with high tumor mutation burden, according to initial findings from the phase III CheckMate-227 trial.

According to results of a pilot study presented at the 2018 AACR Annual Meeting and simultaneously published in the <em>New England Journal of Medicine,</em>&nbsp;neoadjuvant treatment with the PD-1 inhibitor nivolumab (Opdivo) demonstrated a 45% major pathologic response rate in patients with resectable stage I to III non&ndash;small cell lung cancer (NSCLC) irrespective of PD-L1 expression.

Results from the phase III KEYNOTE-189 trial were presented at the 2018 AACR Annual Meeting, indicating that the combination of pembrolizumab with standard chemotherapy in the frontline setting reduced the risk of death by more than 50% in patients with nonsquamous non-small cell lung cancer without&nbsp;<em>EGFR&nbsp;</em>or&nbsp;<em>ALK</em>&nbsp;mutations.

Findings from the phase III ALEX trial were consistent with earlier results on efficacy and adverse events. Investigators said there were superior patient-reported outcomes for the next-generation tyrosine kinase inhibitor (TKI) alectinib (Alecensa) compared to the standard of care TKI inhibitor crizotinib (Xalkori) for patients with ALK-positive non&ndash;small cell lung cancer.

Clinical Approach for Unresectable Locally Advanced NSCLC

According to the results from a phase I study, BLU-667, a next-generation tyrosine kinase inhibitor, was well-tolerated and demonstrated clinical benefit in patients with advanced,&nbsp;<em>RET</em>-altered solid tumors who had progressed on previous therapies. These findings were presented April 14 to 18 at the ASCR Annual Meeting 2018 in Chicago, Illinois.

Similar improvements in quality of life were found with frontline treatment of osimertinib for patients with&nbsp;advanced&nbsp;EGFR-mutant non&ndash;small cell lung cancer, as well as&nbsp;a clinically meaningful improvement in cough, compared with the standard-of-care EGFR TKIs, according to the phase III FLAURA trial. The results were presented at the 2018 European Lung Cancer Congress&nbsp;in Geneva, Switzerland.