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Outcomes with frontline immune checkpoint inhibitors among individuals with BRAF-mutant non-small cell lung cancer
Julian A Marin-Acevedo1, Ram Thapa2,3, Sudeepthi V Bandikatla4,5
1Thoracic Oncology, Division of Hematology and Medical Oncology, Department of Internal Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United States.
Background:
Oncogenic BRAF mutations affect ~4% of non-small cell lung cancer (NSCLC). Class I mutations (i.e., V600) are typically responsive to BRAF/MEK inhibitors, while non-Class I are often resistant. The role of immune checkpoint inhibitors (ICIs) as first-line therapy in BRAF-mutant NSCLC remains unclear.
Methods:
We retrospectively analyzed patients with BRAF-mutant NSCLC treated at Moffitt Cancer Center from January 1, 2012, to August 9, 2023. Demographics, biomarker (e.g., PD-L1, molecular profile), and treatment data were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using standardized real-world endpoints.
Results:
Among 122 individuals, 54 had Class I and 68 had non-Class I mutations. For Class I mutations, ICIs yielded a PFS of 9.2 months and OS of 42.2 months, representing a significant OS advantage over chemotherapy-alone (22.2 months; p = 0.03). Outcomes were comparable to those seen with anti-BRAF/MEK therapy (PFS 14.7 months; p = 0.49, OS NE; p = 0.99), while ICIs trended towards improved OS in those with PD-L1 ≥50% (53.1 vs. 24.8 months; p = 0.61). For non-Class I mutations, ICI benefit was more limited (PFS 11.7 months, OS 18.5 months) yet compared favorably to chemotherapy-alone (PFS 4.7 months; p = 0.01; OS 9.9 months; p = 0.22). No patients with non-Class I mutations received anti-BRAF/MEK therapy.
Conclusion:
ICIs appear effective in BRAF mutant-NSCLC. For Class I mutations, ICIs yielded significant survival benefit over chemotherapy-alone. Outcomes were comparable to anti-BRAF/MEK therapy, with a potential survival advantage favoring ICIs in those with PD-L1 ≥50%. For non-Class I mutations, ICIs benefit was more modest but compared favorably to chemotherapy-alone.
Insights
Immune checkpoint inhibitors (ICIs) show effectiveness in BRAF-mutant non-small cell lung cancer (NSCLC). Class I BRAF mutations benefit significantly from ICIs compared to chemotherapy, with outcomes similar to BRAF/MEK inhibitors.
Area of Science:
- Oncology
- Pulmonology
- Cancer Research
Background:
- Oncogenic BRAF mutations occur in approximately 4% of non-small cell lung cancer (NSCLC) cases.
- Class I BRAF mutations (e.g., V600) generally respond to BRAF/MEK inhibitors, whereas non-Class I mutations often exhibit resistance.
- The efficacy of immune checkpoint inhibitors (ICIs) as a first-line treatment for BRAF-mutant NSCLC is not well-established.
Purpose of the Study:
- To evaluate the effectiveness of immune checkpoint inhibitors (ICIs) in patients with BRAF-mutant non-small cell lung cancer (NSCLC).
- To compare ICI outcomes with chemotherapy-alone and BRAF/MEK inhibitor therapy across different BRAF mutation classes.
- To assess the impact of PD-L1 expression on ICI efficacy in BRAF-mutant NSCLC.
Main Methods:
- Retrospective analysis of 122 BRAF-mutant NSCLC patients treated at Moffitt Cancer Center (2012-2023).
- Collection of demographic, biomarker (PD-L1, molecular profile), and treatment data.
- Estimation of progression-free survival (PFS) and overall survival (OS) using real-world endpoints.
Main Results:
- For Class I BRAF mutations (n=54), ICIs resulted in a PFS of 9.2 months and OS of 42.2 months, significantly outperforming chemotherapy (OS 22.2 months; p=0.03).
- ICI outcomes for Class I mutations were comparable to anti-BRAF/MEK therapy (PFS 14.7 months; p=0.49) and suggested improved OS in PD-L1 ≥50% patients (53.1 vs. 24.8 months; p=0.61).
- For non-Class I BRAF mutations (n=68), ICIs showed a more modest benefit (PFS 11.7 months, OS 18.5 months) but still favored chemotherapy-alone (PFS 4.7 months; p=0.01; OS 9.9 months; p=0.22).
Conclusions:
- Immune checkpoint inhibitors (ICIs) demonstrate efficacy in BRAF-mutant non-small cell lung cancer (NSCLC).
- ICIs provide a significant survival advantage over chemotherapy for Class I BRAF mutations and show comparable outcomes to BRAF/MEK inhibitors.
- For non-Class I BRAF mutations, ICIs offer a survival benefit compared to chemotherapy alone, although the effect is more modest.
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