Systemic Therapy for Small Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update Clinical Insights

In 2023, an evidence-based guideline on the systemic therapy for small cell lung cancer (SCLC) was published by ASCO and Ontario Health (Cancer Care Ontario).1 Recently, an amendment to the guideline was published (Figs 1 and 2), 2 on the basis of the results of the phase III ADRIATIC trial evaluating the efficacy of consolidation immunotherapy after chemoradiotherapy in patients with limited-stage (LS) SCLC 3 and the phase II DeLLphi-301 trial evaluating tarlatamab in relapsed SCLC. 4 This companion article addresses several questions that clinicians may encounter when following the updated guideline recommendations. WHICH PATIENTS WITH LS-SCLC SHOULD BE CONSIDERED FOR CONSOLIDATION THERAPY WITH DURVALUMAB?On the basis of the published data from the ADRIATIC trial, 3 durvalumab consolidation for up to 2 years is recommended for patients with LS-SCLC who have not had progression of disease after completion of curative-intent chemoradiotherapy.Eligibility criteria included: completion of three to four cycles of chemotherapy with cisplatin or carboplatin plus etoposide along with concurrent definitive thoracic radiotherapy; achievement of treatment response or stable disease; WHO performance status (PS) 0-1 after chemoradiotherapy; no active or prior autoimmune disease; no history of pneumonitis of grade ≥2; and resolution of toxicity from prior chemoradiotherapy to grade ≤1.Prophylactic cranial irradiation (PCI) was allowed after completion of chemoradiotherapy and before the start of consolidation therapy.To assess the appropriateness of consolidation durvalumab for an individual patient, it is necessary to understand both the benefits and risks of treatment.Patients were randomly assigned after completion of chemoradiotherapy to receive either durvalumab 1,500 mg once every 4 weeks (n 5 264) or placebo (n 5 266) for up to 2 years, with treatment starting within 42 days of the completion of chemoradiotherapy.With a median follow-up of 37.2 months, the median overall survival (OS) was 55.9 months for durvalumab and 33.4 months for placebo (hazard ratio [HR], 0.73 [98.3% CI, 0.54 to 0.98]; P 5 .01).The OS rates at 36 months were 56.5% versus 47.6% for durvalumab versus placebo, respectively.The median progression-free survival (PFS) was 16.6 months for durvalumab and 9.2 months for placebo (HR, 0.76 [97.2% CI, 0.59 to 0.98]; P 5 .02).The PFS rates at 24 months were 46.2% versus 34.2% for durvalumab versus placebo, respectively.Overall, these data suggest that about 10% of patients will have a long-term survival benefit with durvalumab.All-cause grade 3-4 adverse events (AEs) occurred in 24.4% of patients receiving durvalumab and 24.2% receiving placebo.Treatment-related grade 3-4 AEs were reported in 8.8% of patients receiving durvalumab and 6% of patients receiving placebo.Patients receiving durvalumab had higher rates of AEs leading to drug discontinuation (16.4% v 10.6%) and death (2.7% v 1.9%).Immune-related AEs were reported in 32.1% of patients receiving durvalumab and 10.2% receiving placebo.Pneumonitis (of any cause) of any grade (38.2% v 30.2%) and grade 3-4 (3.1% v 2.6%) also occurred more frequently with durvalumab.Most patients with LS-SCLC treated with definitive chemoradiotherapy have dramatic improvement in their tumor burden and cancer-associated symptoms.Although side effects of treatment, such as fatigue, myelosuppression, and esophagitis, are common, they usually improve within 6 weeks of completion of chemoradiotherapy.Therefore, most patients with LS-SCLC will be candidates for consolidation durvalumab.Although ADRIATIC was limited to

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