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K.A. Schalper
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MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:S. Ishikura, H. Nakayama
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 311 + 312
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MA 13.03 - Quantitative Spatial Profiling of PD-1/PD-L1 Interaction Predicts Response to Adjuvant Chemotherapy Non–Small-Cell Lung Cancer (ID 8419)
15:45 - 17:30 | Author(s): K.A. Schalper
- Abstract
- Presentation
Background:
Adjuvant chemotherapy (ACT) for ES-NSCLC has a modest improvement in survival but it is often associated with serious adverse effects. Thus, identifying subgroups of ES-NSCLC patients who may benefit from ACT is of high clinical relevance. We evaluated the prognostic and predictive role of quantitative spatial profiling of PD-1/PD-L1 interaction in the tumor cells of ES-NSCLC patients.
Method:
451 whole tissue sections of formalin-fixed, paraffin embedded surgical resection specimens from ES-NSCLC patients with/without ACT were tested with a multiplexed fluorescence immunohistochemistry assay to detect PD-1, PD-L1, cytokeratin and DAPI labeling. Fluorescence Images were acquired on the Perkin Elmer Vectra platform and analyzed with AQUA® algorithms to determine the percent positivity of each biomarker as well as the co-localization of PD-1 and PD-L1 (the Interaction Score).
Result:
High PD-1/PD-L1 Interaction Scores correlated with improved progression-free and overall survival for ES-NSCLC patients receiving ACT after surgery (p = 0.01) whereas no difference in survival was observed for patients who received surgery alone (p = 0.9) (Figure 1). Interestingly, the levels of PD-1 or PD-L1 alone did not demonstrate any difference in survival for surgery + ACT or surgery alone patient populations. Figure 1
Conclusion:
PD-1/PD-L1 Interaction Score is predictive of benefit from ACT in patients with ES-NSCLC. Future studies will determine if this tool can be used to select patients that may be spared chemotherapy without compromising outcome.
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MA 15 - Lung Cancer Biology II (ID 670)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
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MA 15.06 - ERBB Receptor Feedback Inhibitor-1 Alterations in Non-Small Cell Lung Cancer (ID 10454)
15:45 - 17:30 | Author(s): K.A. Schalper
- Abstract
- Presentation
Background:
ERBB Receptor Feedback Inhibitor-1 (ERRFI-1) encodes MIG6, which is a negative regulator of EGFR and ERBB2 signaling. Loss of function alterations at ERRFI-1 would be expected to promote oncogenesis, but the role of ERRFI-1 alterations in conferring sensitivity to targeted therapies remains to be fully investigated.
Method:
We reviewed 19,347 cases of NSCLC in the Foundation Medicine data base for ERRFI-1 alterations that had been previously assayed by hybrid-capture based genomic DNA profiling of FFPE tissue specimens. Two patients, so identified, had been treated with EGFR pathway antagonist therapies and their outcomes are reported herein.
Result:
ERRFI-1 truncating mutations were identified in 0.62 % (120/ 19,347) of all screened NSCLC specimens. ERRFI-1 alterations were seen in all NSCLC histologic subtypes examined at similar frequencies: adenocarcinoma (0.7%), squamous carcinoma (0.3%), large cell carcinomas (0.8%), adenosquamous (0.6%), sarcomatoid (0.6%), and not otherwise specified (0.6%). Co-existing alterations included: P53 (59%), KRAS (19%), EGFR exon 19 del (9.2%), EGFR L858R (3.3%), EGFR T790M (3.3%), EGFR amp (6.7%), ERBB2 mut (7.5%), and ERBB2 amp (3.3%). Two female patients with ERRFI-1 mutations who were wildtype for known NSCLC driver mutations and targeted therapy naive, achieved RECIST criteria partial responses after treatment with single agent EGFR TKI therapies. Following subsequent disease progression, one of these patients also achieved a secondary response to single agent EGFR directed monoclonal antibody therapy. To our knowledge, these are the first two reported patient outcomes for targeted therapies in ERRFI-1 altered NSCLC.
Conclusion:
The index cases presented here suggest that NSCLC patients with genetic lesions in ERRFI-1 may respond to both anti-EGFR TKIs and monoclonal antibodies. However, co-occurrence between ERFFI-1 mutations and alterations in known NSCLC drivers such as EGFR exon 19 del and L858R may also indicate that in some contexts, ERRFI-1 alterations may provide a mechanism for acquired resistance to targeted therapies as well. Further investigation including assessment of ERRFI-1 loss of heterozygosity, ERRFI-1 VUSs , and clinical evaluation of additional cases including response and resistance to targeted therapy will be performed to more fully delineate the role of ERRFI-1 in NSCLC.
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