ASCO 2024 Meeting Report — Lung Cancers

The 2024 American Society of Clinical Oncology (ASCO) annual meeting, held May 30 to June 3 in Chicago, highlighted important advances in treatment across a broad spectrum of malignancies. Here, NEJM Journal Watch Oncology and Hematology Associate Editor Jyoti D. Patel, MD, FASCO, reviews key trials in lung cancer.

In patients with unresectable EGFR-mutated stage III non–small-cell lung cancer (NSCLC), osimertinib, a third-generation EGFR tyrosine kinase inhibitor, improved progression-free survival (PFS), according to findings from the industry-sponsored, phase 3 LAURA trial published in the New England Journal of Medicine and presented at the ASCO meeting.

Roughly 200 adults with locally advanced EGFR-mutated NSCLC who had undergone chemoradiotherapy were randomized to receive either daily oral osimertinib (80 mg) or placebo until disease progression or until another discontinuation criterion was met.

Median PFS, the primary end point, was 39.1 months with osimertinib, compared with 5.6 months with placebo (hazard ratio for disease progression or death with osimertinib: 0.16). New brain metastases occurred less often in the osimertinib group (8% vs. 29% of the placebo group).

Some 8% of osimertinib recipients experienced interstitial lung disease, compared with 1% of placebo recipients, while 48% of the osimertinib group and 38% of the placebo group had radiation pneumonitis.

Summary by Kelly Young, Staff Writer

COMMENT — Dr. Jyoti Patel

Osimertinib after chemoradiation in patients with unresectable locally advanced EGFR-mutated NSCLC provides a significantly impactful clinical benefit by decreasing early progression and spread to the brain. This study underscores the importance of biomarker testing in patients with all stages of NSCLC.

Watch our interview with study author Dr. Suresh Ramalingam, Executive Director of Winship Cancer Institute of Emory University.

In treatment-naive patients with advanced ALK-positive non–small-cell lung cancer (NSCLC), lorlatinib improved progression-free survival (PFS) and intracranial activity long term, compared with crizotinib, according to the phase 3, industry-funded CROWN study.

Roughly 300 patients were randomized to receive either 100 mg of lorlatinib, a brain-penetrant, ALK tyrosine kinase inhibitor, or 250 mg of crizotinib once daily. The 5-year PFS was higher in those who received lorlatinib (60% vs. 8% for crizotinib). The median time to intracranial progression was not reached in the lorlatinib arm and was 16.4 months in the crizotinib arm (hazard ratio, 0.06). Among those in the lorlatinib group without brain metastases at study entry, only 4% developed brain metastases, all within the first 16 months of taking the drug.

Grade 3 or 4 adverse events occurred in 77% of those in the lorlatinib group and 57% of those in the crizotinib group, but no new safety signals were reported.

Summary by Kelly Young, Staff Writer

COMMENT — Dr. Jyoti Patel

Lorlatinib is a potent and durable ALK inhibitor. The data represents an important milestone for the treatment landscape of advanced NSCLC. After 5 years of follow-up, the median PFS in the lorlatinib arm has yet to be reached. This is the longest PFS ever reported in advanced NSCLC and highlights the survival gains attained by precision therapy in this disease.

Read more about the study.

In patients with limited-stage small-cell lung cancer (LS-SCLC), consolidation treatment with durvalumab after concurrent platinum-based chemotherapy and radiotherapy improves survival and is well tolerated, according to a planned interim analysis of the industry-sponsored, randomized, placebo-controlled ADRIATIC trial.

In the multinational trial, 730 patients with stage I–III LS-SCLC who had not progressed on chemoradiotherapy were assigned to one of three treatment groups: durvalumab (1500 mg) plus placebo, durvalumab plus tremelimumab (75 mg), or placebo alone every 4 weeks for 4 cycles, followed by durvalumab (in the first two groups) or placebo every 4 weeks for up to 24 weeks or until disease progression or toxicity. Prophylactic cranial irradiation was allowed.

The durvalumab-tremelimumab arm was not included in the primary interim analysis. At approximately 36 months' follow-up, overall survival (OS) was improved with durvalumab compared with placebo: the median OS was 56 versus 33 months and the OS rate was 57% versus 48%, respectively (hazard ratio for death, 0.73). Results were similar for progression-free survival and were largely consistent across subgroups.

The incidence of grade 3–4 adverse events was similar in the durvalumab and placebo arms. No new safety signals were noted.

Summary by Cara Adler, Staff Writer

COMMENT —Dr. Jyoti Patel

Despite the potential for curative therapy in limited-stage SCLC, the standard of care of chemoradiation has remained unchanged for decades and most patients experience recurrence. The addition of durvalumab after chemoradiation for limited-stage SCLC leads to an impactful improvement in survival and represents a new standard of care for this devastating disease.

Read more about the study.