A newly published guideline update from ASCO and Ontario Health provides evidence-based recommendations on the use of systemic therapy for small cell lung cancer (SCLC).1 Recommendations cover where novel agents fit in the treatment landscape, the management of disease in older patients with limited- or extensive-stage disease, as well as the treatment of patients harboring EGFR mutations.
In the past 5 years, there have been several noteworthy advancements in the management of limited- or extensive-stage SCLC. Phase III trials have demonstrated benefits with the addition of an immune checkpoint inhibitor to platinum and etoposide-based systemic therapy in patients with SCLC.2-5
Additionally, in June 2020, the U.S. Food and Drug Administration approved the second-line therapy lurbinectedin for patients who experienced disease progression after first-line platinum-based chemotherapy.6
“Hence, there was a need to update the guidelines in terms of systemic management of SCLC,” said Humera Khurshid, MD, of the Lifespan Cancer Institute at the Rhode Island Hospital, and Guideline Co-Chair.
Guideline Recommendations
The new guideline continues to recommend evidence-based adjuvant systemic therapy for resected SCLC, as well as systemic therapy in conjunction with radiation for resected, limited-stage SCLC. The guideline outlines that adjuvant chemotherapy should comprise four cycles of cisplatin or carboplatin plus etoposide.
Two recommendations include lurbinectedin and topotecan as preferred agents for use in patients with relapsed SCLC with a chemotherapy-free interval of up to 90 days as well as in patients with a chemotherapy-free interval of at least 90 days.
“I think the newer drugs that are coming down the line and the ones that are already here, such as lurbinectedin as second-line therapy, can benefit some patients,” said Greg Kalemkerian, MD, of the Rogel Cancer Center, University of Michigan Health, and Guideline Co-Chair.
The guideline also offers recommendations for SCLC that has transformed as a mechanism of resistance in EGFR-mutated non–small cell lung cancer (NSCLC), although rare. In this population, the guideline specifically recommends the use of carboplatin or cisplatin plus etoposide. Additionally, the guideline states that an EGFR inhibitor could be continued alongside chemotherapy in patients with NSCLC harboring an EGFR mutation that has transformed into SCLC.
In patients with limited- or extensive-stage disease and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2, the guideline recommends standard treatment with concurrent chemoradiotherapy with curative intent and a combination of carboplatin and etoposide plus immunotherapy, respectively.
The guideline also recommends offering initial chemotherapy followed by sequential radiotherapy in patients with limited-stage SCLC and an ECOG PS of 3 to 4. For those with extensive-stage SCLC and an ECOG PS of 3 to 4, chemotherapy is recommended.
In older patients with limited-stage disease and an ECOG PS of 0 to 1, the guideline recommends standard treatment with concurrent chemoradiotherapy with curative intent. In older patients with extensive-stage SCLC and an ECOG PS of 0 to 1, the guideline recommends standard treatment with carboplatin and etoposide plus immunotherapy (eg, atezolizumab or durvalumab) followed by maintenance immunotherapy.
Given that nearly 40% of patients with SCLC are older than age 70, the guideline co-chairs emphasized the importance of improving clinical trial participation among older patients with the disease. “Older patients, especially those over age 80, constitute a smaller percentage of trial participants,” Dr. Khurshid said, “[but there are] very limited data in this specific group.”
Dr. Kalemkerian added that it remains important to know how clinicians can potentially treat older patients optimally “and how we can adjust what most people would consider standard treatments accordingly in those cases.”
Additional Highlights, Future Needs
Dr. Kalemkerian explained there is a need to better contextualize the guideline recommendations with respect to personalized SCLC management. “The one thing everybody needs to keep in mind is the guidelines present an optimal treatment for the optimal patient,” he said, “and we always have to adjust that treatment to the person sitting in front of us in the exam room because guidelines are never enough.”
Future guideline updates may include additional recommendations on personalized treatment decision-making, Dr. Kalemkerian added, noting that an important aspect of SCLC management “that’s going to be coming down the line” will be the increased recognition that there are significant differences among patients with the disease.
“Several groups are doing very good work looking at subset analyses of SCLC and identifying different subgroups of patients who have different molecular characteristics in their tumors,” he said, adding that increased knowledge on this topic will likely be incorporated into future guidelines.
REFERENCES
1. Khurshid H, et al: Systemic therapy for SCLC: ASCO-Ontario Health (Cancer Care Ontario) guideline. J Clin Oncol. October 11, 2023 (early release online).
2. Paz-Ares LG, et al: Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC). 2020 ASCO Annual Meeting. Abstract 9002.
3. Reck M, et al: Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol 34:3740-3748, 2016.
4. Rudin CM, et al: Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer. J Clin Oncol 38:2369-2379, 2020.
5. Nishio M, et al: Subgroup analysis of Japanese patients in a phase III study of atezolizumab in extensive-stage small-cell lung cancer (IMpower133). Clin Lung Cancer 20:469-476.e1, 2019.
6. U.S. Food and Drug Administration: FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. Available at https://www.fda.gov. Accessed November 3, 2023.
Originally published in ASCO Daily News © American Society of Clinical Oncology. ASCO Daily News. October 12, 2023. All rights reserved.
