EGFR+ Lung Cancer

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.

EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases

According to findings presented by Martin Reck, MD, PhD, at the 2018 European Lung Cancer Conference, the frontline regimen of atezolizumab, bevacizumab, carboplatin, and paclitaxel has became a potential new standard of care for the treatment of patients with metastatic nonsquamous non&ndash;small cell lung cancer.

EGFR+ NSCLC

According to 3-year survival findings from the phase II POPLAR study,&nbsp;anti PD-L1 immunotherapy with atezolizumab (Tecentriq) demonstrated strong superiority to&nbsp;docetaxel in locally advanced or metastatic non&ndash;small cell lung cancer.