ASCO and Ontario Health Publish Joint Update on Guideline for Targeted Therapy in NSCLC With Driver Alterations

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ASCO and Ontario Health (Cancer Care Ontario) have jointly published an update1 to the 2017 ASCO guideline2 regarding systemic therapy recommendations for stage IV non–small cell lung cancer (NSCLC) with driver alterations. Guideline Co-Chair Nasser H. Hanna, MD, of the Indiana University Simon Comprehensive Cancer Center, said that this guideline represents the first document devoted to recommendations for systemic therapy in stage IV NSCLC with driver alterations. In addition, emerging clinical trial data and recent approvals of novel agents have made way for the updated guideline recommendations.

“The number of druggable targets has been increasing over the last several years, and the incorporation of targeted therapy in this population provides oncologists with more options for treatment,” Dr. Hanna said. “When to preferentially use a targeted drug instead of chemotherapy, immunotherapy, or chemoimmunotherapy has become an increasingly complex matter.”

Nasser H. Hanna, MD

Nasser H. Hanna, MD

Gregory Masters, MD

Gregory Masters, MD

“We have some well-established targeted drugs and other new targeted therapies that are emerging for a variety of genetic alterations and subtypes,” added Guideline Co-Chair Gregory Masters, MD, of the Helen F. Graham Cancer Center and Research Institute. “It has become increasingly complicated to manage patients in the era of molecular medicine, and this guideline helps provide a framework to offer the best and most up-to-date care for our patients.”

New and Updated Recommendations

The key recommendations made in the update since the publication of the 2017 ASCO guideline discuss treatment options, such as dacomitinib for EGFR mutations, erlotinib plus ramucirumab for EGFR mutations, lorlatinib for patients with ALK fusions, pralsetinib and selpercatinib for patients with RET fusions, capmatinib for patients with MET exon 14 mutations, entrectinib for patients with ROS1 fusions or NTRK fusions, and larotrectinib for NTRK fusions.

Specifically, the new update now recommends osimertinib monotherapy as a first-line approach for patients with EGFR mutations. In 2017, osimertinib was considered as a second-line therapy solely for patients with T790M mutations who received no benefit from a prior EGFR tyrosine kinase inhibitor. The new recommendation for osimertinib is partly based on data from the randomized FLAURA trial, which enrolled patients with sensitizing EGFR mutations. Treatment with osimertinib resulted in a longer progression-free survival benefit compared with standard first-line EGFR tyrosine kinase
inhibitor therapy.

The new guideline also includes an update on treatment for patients with tumors harboring ALK rearrangement. “We now recommend alectinib or brigatinib as standard first-line therapy based on new clinical trials,” Dr. Masters said. In addition, the update includes new sections on MET exon 14–skipping mutations, with corresponding recommendations for capmatinib or tepotinib in the first-line setting.

Also, the guideline now recommends selpercatinib as a standard treatment in the first-line setting of driver alterations in RET. This recommendation was supported by data from the phase II LOXO-292 trial, which involved patients with RET fusion who had prior platinum-based treatment. The progression-free survival was 17 months in patients with prior therapy, whereas it was not estimable in patients who had no prior therapy.

Future Goals and Research Needs

The field of research involving NSCLC with driver alterations is rapidly evolving, Dr. Hanna said. For instance, several studies are currently underway to investigate therapeutic agents for patients with HER2 exon 20 insertion mutations, EGFR exon 20 insertion mutations, MET amplification, NRG fusions, KRAS G12C mutations, and DNA repair–deficient tumors, among others. Findings from these investigations may hold implications for future iterations of the ASCO and Cancer Care Ontario guideline.

“There are multiple areas of research that show promise for treating patients with advanced NSCLC, including those with driver mutations,” Dr. Masters said. “Specific research underway that may influence future guidelines includes treatment for KRAS mutations, particularly the G12C mutation where drugs are being investigated as well as drugs that target HER2, BRAF, and others.”

To improve clinical guidance in NSCLC with driver alterations, Dr. Masters emphasized the need for increased clinical trial participation. Additional studies, he argued, are essential for the identification of more targeted treatments for newly recognized or appreciated mutations. Ultimately, Dr. Masters said, this may further improve patient care.

“It is through basic science discovery, translational research, and clinical trial participation that we have been able to move this field forward so rapidly over the last 5 to 10 years, including development of new and more effective targeted therapies, molecular diagnostics, and immunotherapy; these advances have helped to improve survival of patients with lung cancer when incorporated into therapy along with standard surgery, radiation, and chemotherapy treatments,” Dr. Masters said. 

DISCLOSURE: Dr. Hanna has received honoraria from UpToDate; has received research funding from Merck KGaA, Bristol Myers Squibb, AstraZeneca/MedImmune, and Genentech; and has reported other relationship with BeyondSpring Pharmaceuticals. Dr. Masters reported no conflicts of interest. For full disclosures of other panel members, visit


1. Hanna NH, Robinson AG, Temin S, et al: Therapy for stage IV non-small-cell lung cancer with driver alterations: ASCO and OH (CCO) joint guideline update. J Clin Oncol. February 16, 2021 (early release online).

2. Hanna N, Johnson D, Temin S, et al: Systemic therapy for stage IV non-small-cell lung cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 35:3484-3515, 2017.

Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, February 17, 2021. All rights reserved.