A milestone in biomarker testing and therapies for lung cancer

With advancement in biomarker-driven treatment and targeted therapies for lung cancer, novel strategies are employed to optimize personalized regimens for different subtypes of lung cancer.1 To keep track of the evolving lung cancer management, a symposium regarding biomarker and treatment landscape for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) was held at the World Conference on Lung Cancer 2021.1

Dr. David R. Gandara, MD, Director of Thoracic Oncology Program at the University of California Davis Comprehensive Cancer Center of the United States (US), started by introducing the 2 newly identified biomarkers, namely Kirsten rat sarcoma virus (KRAS) glycine 12 to cysteine (G12C) and epidermal growth factor receptor (EGFR) exon 20, for NSCLC.1 He indicated that approximately 40% of NSCLC patients contained actionable oncogenic drivers, of which, KRAS G12C mutation had shown high prevalence in ever-smokers, regardless of the clinical characteristics.1 All patients with advanced non-squamous NSCLC were recommended to undergo broad molecular testing according to the National Comprehensive Cancer Network (NCCN) guidelines, though the real-world biomarker examination rates remained suboptimal.1 “An oncologist armed with the information on biomarker testing will be more capable of determining the best therapy for patients,” said Dr. Gandara. Apart from tissue biopsy, a variety of liquid biopsy platforms have been established for routine tissue-based diagnosis and identification of acquired resistance mechanisms.1 Dr. Gandara added that liquid biopsy was suggested by the International Association for the Study of Lung Cancer (IASLC) for molecular testing of NSCLC patients, offering an alternative in the event of insufficient tissue biopsy specimens, also providing a dynamic assessment to guide treatment decisions.1

Patients with KRAS G12C-mutated NSCLC were characterized by poor progression-free survival (PFS) and overall survival (OS) outcomes in clinical trials.1 Dr. Alexander I. Spira, MD, PhD, FACP, Site Research Leader and Co-director of Clinical Research Program in Virginia Cancer Specialists Research Institute of the US, shared the findings of a newly approved KRASG12C inhibitor from recent studies.1 Patients with advanced or metastatic NSCLC receiving sotorasib, a first-in-class oral KRASG12C inhibitor, demonstrated rapid, deep and durable responses in the phase 2 single-arm CodeBreaK 100 trial.1 He highlighted that an objective response rate (ORR) occurred in 37.1% of participants (95% CI: 28.6-46.2), while the disease control rate (DCR) was 80.6% (95% CI: 72.6-87.2).1 “One of the notable things is that patients who were heavily pretreated with 3 prior lines of therapy achieved an ORR at 39.3%,” said Dr. Spira. He stated that response to sotorasib and survival outcomes were observed across the patient subgroups, including NSCLC patients with stable, previously treated brain metastases, and a favorable benefit-risk profile was performed with improved dyspnea symptoms during sotorasib treatment.1 Dr. Spira mentioned that the CodeBreaK 101 trial which included 12 different combination treatments with sotorasib has been underway.1

SCLC is an aggressive neuroendocrine cancer with poor prognosis and scanty treatment options.1 Dr. Afshin Dowlati, MD, Director of the Center for Cancer Drug Development in the University Hospitals Seidman Cancer Center and Case Western Reserve University of the US, introduced delta-like ligand 3 (DLL3) as a compelling therapeutic target in SCLC.1 DLL3 was highly expressed on the surface of neuroendocrine tumors in 85% of SCLC patients, regardless of stage.1 Dr. Dowlati illustrated that the bispecific T-cell engager (BiTE), an immune-oncology platform, utilized patients’ T-cells and SCLC cells to induce T-cell proliferation and serial lysis, followed by the apoptosis of tumor cells.1 Tarlatamab (AMG 757), adopting the BiTE technology, was investigated in the first-in-human dose exploration study in relapsed/refractory (R/R) SCLC.1 “In this study, it is interesting to us that the median duration of response (DOR) was 8.7 months, which is significantly longer than 3-4 months in other systemic therapies tried in the second-line settings,” said Dr. Dowlati. He elaborated that a feasible safety profile has been shown with tarlatamab and the confirmed partial response was appeared in 20% of patients according to this interim analysis of the ongoing phase 1 study.1 Dr. Dowlati highlighted that tarlatamab in combination with programmed cell death protein-1 (PD-1) in progressive and recurrent SCLC would be explored in upcoming clinical trials.1

To conclude, the advancement of biomarker testing and targeted therapies in recent years has expanded the treatment options, enabling precision medicine for lung cancer patients.1 With progressive clinical trials regarding the combinations of diversified therapies and agents for different types of lung cancer, it is anticipated that more novel therapies will be available for optimizing patient outcomes.1

  1. Gandara DR, Spira AI, Dowlati A. Advancing the Lung Cancer Landscape With Novel Strategies. Presented at World Conference on Lung Cancer 2021; September 9, 2021.

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