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Nicole Bouchard
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MA13 - Interventional Pulmonology (ID 914)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Interventional Diagnostics/Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 206 AC
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MA13.08 - Discussant - MA 13.05, MA 13.06, MA 13.07 (ID 14631)
11:15 - 11:30 | Presenting Author(s): Nicole Bouchard
- Abstract
- Presentation
Abstract not provided
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-08 - Hyperresponsive Disease: A New Pattern of Response in NSCLC Patients Treated by Anti-PD-1/PD-L1 (ID 13577)
16:45 - 18:00 | Presenting Author(s): Nicole Bouchard
- Abstract
Background
Immune-checkpoint inhibitors are standard of care for stage IV non-small cell lung cancer. Pembrolizumab, an anti-PD-1 monoclonal antibody, boosts the host anti-tumor response. Some patients have a better benefit, especially with strongly positive PD-L1 tumors. To our knowledge, hyperresponsive disease has never been reported.
a9ded1e5ce5d75814730bb4caaf49419 Method
We present 3 of these cases.
4c3880bb027f159e801041b1021e88e8 Result
A 52-year-old woman with lung adenocarcinoma with peritoneal carcinomatosis presented to her community hospital for vomiting and abdominal pain of 3-days duration. She had received first-line chemotherapy (carboplatine-pemetrexed) and after progression, was switched to pembrolizumab, started 10 days ago. PD-L1 expression was 100%. Narcotics and antiemetic medications relieved her severe symptoms, but she required hospitalization for 11 days. She did not receive any corticosteroid medication. Medical team was considering palliative care. Three weeks later, imaging showed an almost complete response. Pembrolizumab was restarted, without any gastrointestinal symptoms, with an ongoing response persisting after 13 cycles.
A 73-year-old man with lung adenocarcinoma with bone metastases was started on first-line pembrolizumab. PD-L1 expression was 100%. Two weeks later, he had severe pelvic pain where a bone metastasis had been previously diagnosed, not treated with radiation therapy. He required a 3-weeks hospitalization, with palliative care for pain control. Imaging showed three weeks later a major regression. He was rechallenged with pembrolizumab without recurrent symptoms, currently receiving his 9th cycle.
A 74-year-old man with squamous cell lung cancer with bone and liver metastases was started on first-line pembrolizumab. PD-L1 expression was 95%. Three weeks later, he had severe nausea and vomiting lasting two weeks, not relieved by outpatient antiemetic medications. He was hospitalized for IV medications during 8 days. While hospitalized, imaging showed a major regression of the lung and liver lesions. He even needed corticosteroid medication to decrease his symptoms for 2 weeks. He was rechallenged without recurrent symptoms.
No other etiologies were identified for the symptoms of these 3 patients, including immune-related adverse event (especially endocrine and liver tests), radiation therapy, infection, disease progression or medications. We diagnosed hyperresponsive disease on the basis of the severe symptoms, impressive response on the CT scan and rechallenge with the same medication without recurrent symptoms.
8eea62084ca7e541d918e823422bd82e Conclusion
A major response to immune checkpoint inhibitors may mimic a progressive disease. Severe symptoms related to the tumor locations should not systematically be attributed to local progression. Clinicians should suspect the possibility of a hyperresponsive pattern and prescribe imaging to confirm or refute this hypothesis.
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-23 - Baseline Plasma Biomarkers Predict Long-Term Responses to ALK-TKIs in ALK+ Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 13458)
16:45 - 18:00 | Author(s): Nicole Bouchard
- Abstract
Background
Median progression free survival (PFS) for ALK tyrosine kinase inhibitors (ALK-TKIs) range from 10.9-25.7 months (mos)[1],[2],[3],[4]. While most ALK+ NSCLC patients develop resistance to ALK-TKIs within 1-2 years, a subset of patients experience a response >2 years. Given the lack of proteogenomic markers predicting long-term responses to ALK-TKIs, we conducted whole-exome sequencing (WES) and proteomic profiling to define molecular determinants that could predict a long-term ALK-TKI response, help guide the sequentiality of therapies and optimize treatment strategies.
[1]Soria, J.C. et al. Lancet389,917–929 (2017)
[2]Peters, S. et al. N. Engl. J. Med.377, 829-838(2017)
[3]Kim, D.-W. et al.J. Clin. Oncol.35,2490–2498 (2017)
[4]Solomon, B. J. et al.N. Engl. J. Med.371,2167–2177 (2014).
a9ded1e5ce5d75814730bb4caaf49419 Method
Twenty-four patients with advanced ALK+ NSCLC were enrolled in our study. WES was performed on primary and post-treatment metastatic tissue to identify genomic aberrations and ALK fusions. MRM-MS was used to analyze 327 protein candidates in plasma collected from patients at baseline.
4c3880bb027f159e801041b1021e88e8 Result
Patients were categorized into 3 groups based on duration of response: long-term responders [LR; PFS ≥24 mos (n=8)], normal responders [R; 3 < PFS < 24 mos (n=10)] and non-responders [NR;PFS <3 mos (n=6)]. At data cutoff (30 April 2018), median PFS was 1.6 mos for NR, 11.7 mos for R and 37.1 mos for LR. Two LR remain on treatment and have experienced a PFS > 37.4 mos. Despite detecting novel ALK fusion partners, multiple somatic mutations and copy number aberrations by WES, we could not define a genomic signature predictive of a long-term response to ALK-TKIs from our small cohort. However, MRM-MS identified 15 proteins differentially regulated between LR and NR, including SODE, F13A, LYAM1, FCGBP, PGBM and LUM. Differences in protein levels were further pronounced between LR and NR. To determine whether our protein signature can discriminate according to response groups, we performed principal component and hierarchical clustering analyses. Both analyses successfully segregated LR from R and NR. Moreover, we used our set of 15 proteins to generate single-sample Gene Set Enrichment Analysis scores which distinguished LR from R and NR as distinct groups.
8eea62084ca7e541d918e823422bd82e Conclusion
Targeted proteomic profiling of baseline plasma from ALK+ NSCLC patients identified a protein signature that may predict a long-term response or resistance to ALK-TKIs. A collaboration is in development to confirm the validity of this protein signature in a larger cohort, and with next-generation ALK-TKIs.
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