2024 Best of ASCO Memphis: Dr Iams Discusses Results from the LAURA Trial in Non-Small Cell Lung Cancer
Presenter:
Wade Iams, MD, MSCI, Tennessee Oncology
Meeting:
ASCO Direct™ Memphis
The Bottom Line:
Targeted therapy is an important component of treatment for patients with stage III non-small cell lung cancer (NSCLC) that is not amenable to curative surgery (unresectable), however, the optimal duration of targeted therapy after an initial curative treatment is debated. The LAURA trial investigated the use of a targeted therapy (osimertinib) in patients with unresectable epidermal growth factor receptor mutated (EGFRm) NSCLC. Results from the trial show that the use of osimertinib, indefinitely, after initial chemoradiation treatment improved progression free survival relative to placebo.
Background
Osimertinib is an orally administered tyrosine kinase inhibitor (TKI), a type of targeted therapy, that is approved for patients with unresectable, epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC). In his recent presentation at the 2024 Best of ASCO Memphis Conference, Dr Wade Iams, MD, MSCI from Tennessee Oncology highlighted some practice impacting results from the LAURA Trial, as presented at this year’s Annual Meeting of the American Society for Clinical Oncology (ASCO).
Trial Design and Patients
The LAURA Trial enrolled patients with locally advanced, unresectable, EGFRm NSCLC who were without progression following first line treatment with definitive chemoradiation. Patients were randomized to treatment with osimertinib, once daily, indefinitely, or placebo. The primary endpoint in the trial was progression-free survival (PFS) with secondary endpoints of overall survival (OS) and PFS in the central nervous system (i.e., freedom from brain metastases). Patients in the trial were roughly equally split with their type of EGFR mutation (either Ex19Del or L858R), most were either clinical stage IIIA or IIIB, and most had received their chemoradiation concurrently (at the same time). Dr Iams noted that the use of prior sequential chemoradiotherapy was also allowed in the trial, which is sometimes needed if patients have poor performance status. Importantly, if patients had progression while on placebo, the trial design allowed them to cross over to osimertinib treatment.
Main Trial Results
Results reported at ASCO 2024 showed a median PFS of 39.1 months in the osimertinib arm, versus 5.6 months in the placebo arm, and the difference was statistically significant (hazard ratio [HR]=0.16; P<0.001). At the time of this analysis, the difference in OS had not reached statistical significance (median OS, 54 months, versus not reached; P=0.530), however, Dr Iams noted that at the time of this analysis, most (81%) of patients in the placebo arm had crossed over to treatment with osimertinib, in accordance with the trial design. As such, the OS results could have been affected, and it will require a longer follow up to determine the impact of indefinite osimertinib on survival. Notably, of 143 patients in the osimertinib arm, 8 patients (5.6%) had new brain lesions, as compared to 29 of 73 patients (39.7%) in the placebo arm. The number of patients with brain, lung, liver, and lymph node metastases was also numerically lower with osimertinib relative to placebo (Box 1).
Box 1. Sites of Metastasis (New Lesions) in the LAURA Trial
| Sites of New Lesions | Osimertinib Arm (n=143) | Placebo Arm (n=73) |
|---|---|---|
| Total New Metastatic Lesions | 22 | 68 |
| Brain | 8 | 29 |
| Lung | 6 | 29 |
| Liver | 3 | 7 |
| Lymph Nodes | 1 | 7 |
| Bone | 1 | 1 |
Adverse Events and Toxicities
Radiation pneumonitis (lung infection) is a concern when treating patients with osimertinib after concurrent chemoradiation, and in LAURA, this was the most common adverse event in both arms, although the majority of events were of low grade and were manageable, with no grade 4 or 5 events. Diarrhea, rash, and Covid-19 infection were also more common in the osimertinib arm.
Conclusions and Faculty Insights
In view of the results of the LAURA Trial, Dr Iams considers indefinite osimertinib treatment as the new standard of care for patients who have received definitive chemoradiation. In particular, he noted that brain metastases are commonly seen in patients with EGFRm NSCLC upon recurrence (for example, 40% of the patients on the placebo arm of LAURA recurred in the brain), and the reduction in brain lesions that was seen for patients on osimertinib versus placebo (Box 1). In addition, despite the lack of significant OS benefit for indefinite osimertinib in the trial, Dr Iams noted that many patients may prefer to take an orally administered medication with an overall manageable safety profile as a means to prevent such recurrences. “This is one of the strong arguments, in my practice, in my opinion, that we should treat all patients with osimertinib consolidation after curative intent chemoradiation…”
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Speaker Disclosure information: Dr Iams reported the following disclosures for this presentation: Advisory Board/Consulting:Merus, BMS, Daichii Sankyo, Guardant, Tempus, EMD Serono, Amgen, Sanofi, NovoCure, Genentech, AstraZeneca, Catalyst, Jazz Pharma, Elevation Oncology, Janssen, Takeda, Mirati, G1 Therapeutics.