Clinical Application of Precision Oncology in Lung Cancer

Presented by: Millie Das, MD

Covered by: Ivy Riano, M.D., Research Chief Fellow, Hematology and Oncology Unit, Dartmouth Cancer Center, Lebanon, NH.

 

Dr. Millie Das, Chief of Oncology at the Palo Alto VA Health Care System, discusses how non–small cell lung cancer (NSCLC) has become a prominent example of precision medicine among solid tumor malignancies. To date, FDA-approved therapies for oncogenic driver mutations are expanding. Dr. Das presented the latest updates of tyrosine kinase inhibitors (TKIs) as the standard of care for patients with activated EGFR mutations in NSCLC.

She provides an overview of pivotal studies, including the IPASS study, the first to conclude that patients with EGFR mutations should be identified early on and receive an EGFR TKI upfront [1], and the ADAURA trial, which granted FDA approval of osimertinib as an adjuvant treatment for early stage resected EGFR-mutated NSCLC [2].

 

Importantly, Dr. Das highlights that resistance to targeted therapy is inevitable, and next-generation drugs are certainly more challenging to overcome those mechanisms. After an initial benefit with the use of EGFR inhibitors, approximately 60% of the patients develop T790M mutation or other mechanism such as EGFR amplification concurrent with T790M, HER2, MET amplifications, and others [3,4]. Consequently, there are treatment strategies in development to delay or overcome EGFR TKI resistance. The CHRYSALIS-2 study assesses the bispecific antibody targeting MET and EGFR amivantanab given in combination with the 3^rd-generation EGFR TKI lazertinib for patients with disease progression after receiving osimertinib and platinum-based chemotherapy. Findings of CHRYSALIS-2 showed encouraging responses for pretreated patients with EGFR-mutant NSCLC [5]. The ongoing phase 3 MARIPOSA study is also further investigating amivantanab plus lazertinib vs. osimertinib vs. lazertinib in previously untreated, EGFR-mutated, advanced NSCLC.

 

Dr. Das concludes that the increasing understanding of cellular biology of driver alterations will help develop therapies with high selectively and specificity.

 

 

1. Mok et al. NEJM 2009.
2. Herbst et al. NEJM 2020.
3. Yu H et al. Clin Cancer Res 2013.
4. Ramalingman et al. ESMO 2018.
5. Shu et al. ASCO 2020.