A new ASCO guideline rapid update provides updated recommendations for the management of stage III non–small cell lung cancer (NSCLC). These updated recommendations made by the ASCO expert panel cover treatment options for patients with resected disease and specific genetic mutations as well as therapeutic management approaches for patients who are planned for surgical resection.1
New Data and Updated Recommendations
According to Guideline Co-Chair Megan E. Daly, MD, of UC Davis Health, the management of stage III NSCLC has rapidly evolved in the time following the original stage III guideline, due to the publication of several practice-changing trials.2
Guideline Co-Chair Navneet Singh, MD, DM, FASCO, of the Postgraduate Institute of Medical Education & Research in Chandigarh, India, added that these recent trials involving patients with stage III NSCLC have prompted the new rapid guideline update, given their promising data. These trials include the ADAURA trial as well as two trials (CheckMate 816 and KEYNOTE-671) that have explored the use of PD-L1 receptor immune checkpoint inhibitor therapy in combination with chemotherapy as neoadjuvant treatment of potentially resectable stage I–III NSCLC.3-6
Megan E. Daly, MD
Navneet Singh, MD, DM, FASCO
One of the key updated recommendations by the ASCO panel was based on recent overall survival data from the phase III ADAURA trial. The trial evaluated overall survival with 3-year adjuvant osimertinib vs placebo in a total of 682 patients with completely resected EGFR-mutated (exon 19 deletion and exon 21 L858R) stage IB–IIIA NSCLC.3,4 Data from the ADAURA trial showed that the 5-year overall survival rate was significantly higher with adjuvant osimertinib vs placebo (85% vs 73%) in stage II–IIIA disease after a median follow-up periods of 60 months for osimertinib and 56 months for placebo.4
Based on data from the ADAURA trial, the ASCO panel now recommends offering adjuvant osimertinib after platinum-based chemotherapy in patients with resected stage III NSCLC with EGFR exon 19 deletion or exon 21 L858R mutation. “It is important to highlight here that osimertinib treatment in stage III NSCLC should be initiated following completion of adjuvant chemotherapy,” Dr. Singh said.
Additionally, data from the phase III CheckMate 816 and KEYNOTE-671 trials informed development of an updated recommendation on management of patients with stage III NSCLC planned for surgical resection. Briefly, the CheckMate 816 and KEYNOTE-671 trials demonstrated benefit with chemoimmunotherapy (nivolumab plus platinum-doublet chemotherapy and neoadjuvant pembrolizumab with cisplatin-based chemotherapy, respectively) prior to surgical resection with respect to event-free survival.5,6
The ASCO guideline panel wrote that these data indicate the chemoimmunotherapy “strategy represents a new standard of care for potentially resectable NSCLC.” As such, the updated guideline now recommends the use of neoadjuvant chemoimmunotherapy, neoadjuvant chemotherapy, or neoadjuvant concurrent chemoradiation therapy in patients with stage III NSCLC who are planned for surgical resection.
“For patients with stage III NSCLC, all three trials that formed the basis for this rapid update indicate very encouraging developments,” Dr. Singh said. The neoadjuvant chemoimmunotherapy approach is now the standard of care for potentially resectable stage III NSCLC, he added, given that this combination “has been shown to be superior to chemotherapy alone in terms of higher probability of achieving a complete or major pathologic tumor response as well as improving recurrence or event-free survival following surgical resection.”
What Clinicians Should Know
According to Dr. Singh, biomarker testing is a key component of stage III NSCLC and should be on top of mind among clinicians who are implementing the updated recommendations. “It is important for clinicians involved in the management of lung cancer to realize the importance of biomarker testing,” he said, “something that was initially believed to have relevance only for metastatic disease.”
Dr. Singh added that with the availability of data indicating benefit with immunotherapy and targeted therapy in metastatic disease and early-stage as well as locally advanced disease, clinicians should ensure that biomarker testing “by approved and validated methods” is performed in all patients with stage I–III NSCLC. Biomarker testing should be particularly focused on EGFR mutation and PD-L1 expression, he added.
“Biomarker testing is important to decide and select patients for the appropriate biological therapy to be used in conjunction with or following chemotherapy,” Dr. Singh said. “I need to clarify here that the spectrum of biomarker testing recommended for metastatic disease is much larger than what is currently being advocated for early or locally advanced NSCLC.”
Remaining Questions
Although the updated recommendations represent a culmination of key data from recently published trials, the dynamic nature of clinical research will undoubtedly provide further guideline revisions. “Over the next several years, we expect to see data around the use of osimertinib in patients with stage III treated nonsurgically with chemoradiation with EGFR mutations,” Dr. Daly said. “The role of other targeted therapies in stage III disease should also be explored.”
Dr. Singh said the ASCO panel “eagerly awaits” overall survival data from the neoadjuvant chemoimmunotherapy trials. These data could provide critical information to fill current knowledge gaps regarding these treatment approaches in stage III NSCLC.
Furthermore, Dr. Singh commented that there are several unanswered questions remaining, but there is hope that ongoing research will attempt to provide much-needed answers to these clinical questions. One question, Dr. Singh said, is whether adjuvant immunotherapy is beneficial for patients who have already received neoadjuvant chemoimmunotherapy and, if so, determining the optimal duration for the treatment approach.
Also, Dr. Singh suggested there is a need to identify whether the 3-year adjuvant osimertinib duration is appropriate for all patients. If a shorter duration of treatment can suffice for a subgroup of patients, Dr. Singh and the panel want to know whether it would also lead to a reduction in both treatment costs and potential treatment-related adverse effects.
REFERENCES
1. Singh N, Daly ME, Ismaila N, et al: Management of stage III non–small-cell lung cancer: ASCO guideline rapid recom-
mendation update. J Clin Oncol. July 20, 2023 (early release online).
2. Daly ME, Singh N, Ismaila N, et al: Management of stage III non–small-cell lung cancer: ASCO guideline. J Clin Oncol 40:1356-1384, 2022.
3. Herbst RS, Wu YL, John T, et al: Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non–small-cell lung cancer: Updated results from the phase III randomized ADAURA trial. J Clin Oncol 41:1830-1840, 2023.
4. Herbst RS, Tsuboi M, John T, et al: Overall survival analysis from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR‑mutated stage IB–IIIA non–small-cell lung cancer. 2023 ASCO Annual Meeting. Abstract LBA3.
5. Forde PM, Spicer J, Lu S, et al: Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med 386:1973-1985, 2022.
6. Wakelee H, Liberman M, Kato T, et al: Perioperative pembrolizumab for early-stage non–small-cell lung cancer. N Engl J Med. June 3, 2023 (early release online).
Originally published in ASCO Daily News © American Society of Clinical Oncology. ASCO Daily News, July 26, 2023. All rights reserved.
