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Paul Paik
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MA17 - Molecular Mechanisms and Therapies (ID 143)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:Eloisa Jantus-Lewintre, Hongbin Ji
- Coordinates: 9/09/2019, 15:45 - 17:15, Melbourne (1991)
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MA17.08 - Discussant - MA17.05, MA17.06, MA17.07 (Now Available) (ID 3787)
15:45 - 17:15 | Presenting Author(s): Paul Paik
- Abstract
- Presentation
Abstract not provided
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-39 - Molecular Characteristics, Immunophenotype, and Immune Checkpoint Inhibitor Response in BRAF Non-V600 Mutant Lung Cancers (ID 1529)
09:45 - 18:00 | Author(s): Paul Paik
- Abstract
Background
Targeted therapy for Class I BRAF mutant lung cancers (V600) is well described and there is growing literature on their response to immune checkpoint inhibitors (ICI). In contrast, the molecular characteristics, immunophenotype, and response rates of class II and III BRAF mutations are not well defined.
Method
Patients with BRAF Class I, II, III mutant and variants of unknown significance (VUS) lung cancers detected on NGS (MSK-IMPACT) from 1/2014-1/2018 were identified. PD-L1 by immunohistochemistry (E1L3N) was evaluated. Tumor mutation burden (TMB; mut/Mb) was determined by MSK-IMPACT. Best objective response to ICI was assessed by RECIST v1.1. Time to treatment discontinuation (TTD) and overall survival (OS) were assessed. Statistical analysis was performed with Fisher’s exact and Kaplan-Meier. BRAF V600 lung cancers were used as a comparator and analyzed separately from BRAF non-V600.
Result
6.0% (177/2962) of lung cancers harbored a BRAF-mutation. Median TMB of BRAF non-V600 mutant lung cancers was 10.8 mut/Mb (n=136) overall compared to 4.9 mut/Mb in V600 (n=41; p<0.0001) and 5.9 mut/Mb in BRAF wild-type patients (n=2785; p<0.0001). 69% (127/177) of BRAF-mutant cases were metastatic (29 Class I, 36 Class II, 23 Class III, and 39 VUS). 57% of patients were female, 82% were smokers, and 90% were adenocarcinoma. More smokers were seen in the BRAF V600 group than in the non-V600 group (n = 16 vs 88 respectively, p<0.0001). PD-L1 expression in 49 non-V600 cases with available tissue was 0%, 1-49%, and >50% in 59% (n=29), 31% (n=15), and 10% (n=5) respectively. 7 BRAF V600 cases with PDL1 testing had expression of 0%, 1-49%, and >50% in 2, 3, and 2 cases, respectively. No BRAF V600 cases had concurrent RAS/NF1-alterations compared to 11 non-V600 (p=0.07).
36 patients with BRAF non-V600 mutations received ICI (nivolumab (n=25), pembrolizumab (n=5), atezolizumab (n=2), ipilimumab/nivolumab (n=4); median line of therapy=2) with an ORR of 22% (8/36). 10 BRAF V600 mutant lung cancer patients received ICI (nivolumab (n=5), pembrolizumab (n=2), atezolizumab (n=1), ipilimumab/nivolumab (n=2); median line of therapy=2) with an ORR of 10% (1/10). There was no difference in ORR between non-V600 and V600 patients that received ICI (p=0.66). TTD in BRAF non-V600 was 3.2 months compared to 1.4 months for BRAF V600 mutant lung cancer patients (HR 0.59, p=0.26). Median TMB in patients with BRAF non-V600 mutations that responded vs those who did not was 13.2 and 10.8 mut/Mb respectively (p=0.92). One response to ICI was seen in a BRAF V600 with TMB of 19.3. OS of BRAF non-V600 patients was 1.7 years compared to 2.5 years in V600 (HR 1.25, p=0.38). OS was higher in BRAF non-V600 lung cancer patients who received ICI (2.4 years) compared to those that did not (1.2 years; HR 0.60, p=0.04).
Conclusion
The molecular characteristics and immunophenotype of BRAF non-V600 mutant lung cancers is typified by high TMB and low PD-L1 expression, with reasonably higher response rates and improved OS to later line ICI compared to BRAF V600. Further studies of immunotherapy in this oncogene subset is warranted.
