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Feliciano Barron
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MA 12 - Circumventing EGFR Resistance (ID 665)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Wan Ling Tan, Nobuyuki Yamamoto
- Coordinates: 10/17/2017, 11:00 - 12:30, F205 + F206 (Annex Hall)
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MA 12.10 - Clinical Utility of Plasma EGFR T790M Mutation Detection in Advanced Non-Small Cell Lung Cancer Patients According to RECIST Criteria (ID 9620)
12:05 - 12:10 | Author(s): Feliciano Barron
- Abstract
- Presentation
Background:
Circulating tumor DNA (ctDNA) has emerged as a specific and sensitive blood based biomarker for detection of several mutations in non–small cell lung cancer (NSCLC). Other clinical applications for ctDNA include molecular assessment of patients at diagnosis and serial (real-time) monitoring of biomarker status or the development of resistance mutations.
Method:
Eighty patients with advanced NSCLC who either (Group 1) had a new diagnosis or (Group 2) had developed acquired resistance to an EGFR kinase inhibitor were analyzed with highly sensitive Biocept, Inc. TargetSelector[TM] Real Time PCR based plasma assays genotyping for the detection of EGFR mutations L858R, Del19 and T790M. In addition, group 1 was analyzed for KRAS, BRAF, ROS1 and ALK and circulating tumor cells (CTCs) before and after TKI treatment.
Result:
Our results showed concordance rates of EGFR, KRAS and ALK mutations for up to 90% between the tissue and blood samples in newly diagnosed patients (Group 1). Paired analysis of mutations status monitoring in this group (P= 0.016) showed that the pattern of mutant ctDNA and CTCs changed in response to systemic therapy in 83% of the cases (Partial response or disease progression; R2=0.808). Plasma ctDNA analysis of multiple mutations showed that 40% of patients had at least one more mutation besides the one detected in tissue biopsy; 28% of EGFR tissue positive patients also had a KRAS mutation. In addition, 75% of KRAS positive patients had a BRAF mutation. These results demonstrate that plasma ctDNA analysis may even detect mutations missed by standard tissue genotyping due to tissue heterogeneity. Plasma EGFR T790M mutation was analyzed in patients with clinical progression to TKI inhibitors. Considering the RECIST criteria, 58% of progressive disease, 10% of stable disease and 16% of partial response patients were positive for T790M. According to metastatic disease type (locoregional, oligometastatic, polimetastatic), the T790M mutation was found on 64.3% of polimetastatic patients, 30.8% of oligometastatic patients and 17.6% of loco-regional patients.
Conclusion:
TargetSelector[TM] ctDNA assay is capable of rapidly detecting EGFR, KRAS and ALK mutations and is highly concordant with mutations present in tumor tissue with the robustness needed for real world testing to identify patients who progress on first line TKI therapy as well as for real-time monitoring of patients’ clinical status. Our findings highlight the importance of the RECIST criteria to define the progressive disease and determine the right moment to test for T790M mutation regardless the metastatic disease type.
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P3.14 - Radiotherapy (ID 730)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.14-012 - Risk of Developing Pneumonitis Increases in Patients Receiving Immunotherapy with a History of Lung Irradiation (ID 10344)
09:30 - 09:30 | Presenting Author(s): Feliciano Barron
- Abstract
Background:
A large proportion of patients with locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC) present disease progression despite aggressive treatments and will further receive immunotherapy. Pneumonitis is an uncommon but potentially fatal toxicity related to immunotherapy treatment. The association with the history of radiotherapy and the risk of developing pneumonitis have not been well described. We associated the history of radiotherapy with the development of pneumonitis in patients receiving immunotherapy.
Method:
Clinical information was retrospectively obtained from histologically confirmed advanced NSCLC patients treated from February 2013 to February 2017. Clinical and radiologic features of pneumonitis were collected from patients receiving immunotherapy. We sought associations between pneumonitis incidence and clinical characteristics.
Result:
Of 59 patients who received immunotherapy 61.7% were treated with nivolumab, 29.9% with pembrolizumab and 6.7% with the combination durvalumab plus tremelimumab. Immunotherapy treatment was administered in first line in 26.6% of patients, 28.3% received in second line and 36.7% in third or more line of treatment. Twenty-five of the 59 patients (41.7%) received previous radiotherapy, 16 of them (26.7%) to the lung and 9 (15%) to the thoracic spine. Fifteen (15/59) patients (25%) developed pneumonitis; this occurred irrespective of line of therapy in which immunotherapy was received (first line: 38.5%; second line: 33.5%; third line or more: 26.7%). No association was found between line of treatment and pneumonitis development. Median time from therapy initiation to pneumonitis was 4.5 months (range 18 days - 13.1 months). For any grade of pneumonitis, the percentage was of 25% (15 patients) of which 48% (12/25) had received radiotherapy, Grade >2 pneumonitis was seen in 10 patients (17%) and 32% (8/25) had history of radiation therapy. All Grade 3 pneumonitis events (n=4) presented in patients with previous lung radiotherapy. The incidence and severity of pneumonitis was higher in patients who had received radiotherapy (OR, 95% CI: 6.8 (1.6 – 28.5); p=0.009).
Conclusion:
The incidence of pneumonitis related to immunotherapy treatment could be underestimated. We observed an increase in the risk and severity of pneumonitis in patients with previous radiation therapy and subsequent treatment with immunotherapy, regardless of used drug or line of therapy. In these patients, we recommend close clinical and radiologic follow-up.
