ASCO has updated its living guidelines for therapy for stage IV non–small cell lung cancer (NSCLC) with and without driver alterations based on newly available evidence in the field.1,2
“Living guidelines are becoming more important as the field of oncology expands and developments occur more rapidly,” said Expert Panel Co-Chair Dwight Owen, MD, MS, of The Ohio State University, who prepared the recommendations. “Part of that process is to regularly review the literature that is published and new data that are presented in order to meet the needs of clinicians looking for guidance.”
Last updated in July 2022, the most recent update includes two new recommendations for NSCLC with driver alterations and one for NSCLC without driver alterations. All recommendations are reviewed by the expert panel, which works to make sure any recommendation is based on evidence and provides a tier of confidence in that evidence.
Dwight Owen, MD, MS
Managing NSCLC With Driver Mutations
For NSCLC with driver alterations, the first new recommendation is for patients with advanced NSCLC and an activating EGFR2 (HER2, ERBB2) mutation.1 Patients who meet these criteria and who have received prior systemic therapy may be offered trastuzumab deruxtecan.
This recommendation is based on results from the DESTINY-Lung01 trial, an open-label, phase II trial testing fam-trastuzumab deruxtecan-nxki in this patient population.3 Among 91 patients, 55% had a confirmed objective response, with a median duration of response of 9.3 months and a median overall survival of 17.8 months.
This recommendation is evidence-based with the evidence ranked as low and the strength of the recommendation considered weak.
“This subset of patients is not particularly common, but it is still important that patients be tested for this mutation and, if positive, that this option be made available to them,” Dr. Owen said.
The second recommendation is to offer single-agent sotorasib to patients with advanced NSCLC and a KRAS G12C mutation who have received prior systemic therapy.
This recommendation is based on results from CodeBreaK100, an open, label, phase II trial of sotorasib in this patient population, which showed a 37.1% objective response rate with a median overall survival of 12.5 months.4
This recommendation is evidence-based with the evidence ranked as low and the strength of the recommendation considered weak.
Follow-up studies—DESTINY-Lung02 and CodeBreaK200—were both recently presented in abstract form, but the expert panel will await publication of the full results before updating the guideline further.
“It is an exciting time for NSCLC in both the metastatic and early-stage settings, where we are seeing paradigm-changing results, sometimes several times a year,” Dr. Owen said. “We continue to look at new data on new targets for precision approaches and results from studies looking at how best to introduce these targeted therapies.”
Managing NSCLC Without Driver Mutations
The updated recommendation in patients with NSCLC without driver mutations affects only a small subset of patients, Dr. Owen noted.
“Before the introduction of immunotherapy, the standard approach was platinum doublet chemotherapy followed by pemetrexed maintenance for nonsquamous NSCLC,” Dr. Owen said. “Maintenance pemetrexed had been shown to have a benefit after induction chemotherapy, but the question was whether there was any benefit from the addition of bevacizumab to either induction or as maintenance.”
The new recommendation is that bevacizumab should not be added to pemetrexed plus carboplatin or given as maintenance with pemetrexed for patients who do not have contraindications to bevacizumab in patients with nonsquamous NSCLC. This recommendation was given with a moderate level of evidence and weak strength of recommendation.
The guidance is based on a meta-analysis of four randomized controlled trials that showed no overall survival benefit for maintenance therapy with anti-VEGF in addition to pemetrexed compared with pemetrexed alone, and more toxicities.5
“Even though this is a subset of patients we rarely encounter—that is, patients who are not candidates for upfront immunotherapy alone or combined with chemotherapy—we felt it was important to clarify that there was no survival benefit, increased toxicity, and no clearly identifiable biomarker to identify patients who could benefit from maintenance VEGF therapy in combination with pemetrexed,” Dr. Owen said.
References
1. Owen D, Singh N, Ismaila N, et al: Therapy for stage IV non-small cell lung cancer with driver alterations: ASCO living guideline, version 2022.2. J Clin Oncol. December 19, 2022 (early release online).
2. Owen D, Singh N, Ismaila N, et al: Therapy for stage IV non-small cell lung cancer without driver alterations: ASCO living guideline, version 2022.2. J Clin Oncol. December 19, 2022 (early release online).
3. Li BT, Smit EF, Goto Y, et al: Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med 386:241-251, 2022.
4. Skoulidis F, Li BT, Dy GK, et al: Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med 384:2371-2381, 2021.
5. Garon EB, Peterson P, Rizzo MT, et al: Overall survival and safety with pemetrexed/platinum +/- anti-VEGF followed by pemetrexed +/- anti-VEGF maintenance in advanced nonsquamous non-small-cell lung cancer: A pooled analysis of 4 randomized studies. Clin Lung Cancer 23:253-263, 2022.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, December 20, 2022. All rights reserved.
