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Hector Josè Soto Parra
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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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P1.01-53 - Bone Metastases and Efficacy of Immunotherapy in Patients with Pretreated Advanced Non-Small-Cell Lung Cancer (NSCLC) (ID 11980)
16:45 - 18:00 | Author(s): Hector Josè Soto Parra
- Abstract
Background
Approximately 40% of NSCLC patients develop bone metastases (BoM). Bone has active functions in regulating immune system. To date, no trial evaluated the role of BoM in modulating response to immunotherapy. Aim of the present study was to investigate whether presence of BoM impact on immunotherapy efficacy.
a9ded1e5ce5d75814730bb4caaf49419 Method
Two different cohorts of pretreated NSCLC patients (cohort A: Non-squamous; cohort B: Squamous) were evaluated for nivolumab efficacy in terms of objective response rate (ORR), progression free survival (PFS), and overall survival (OS) according to presence or absence of BoM. All patients received nivolumab at standard dose of 3 mg/kg every 2 weeks within the Italian Expanded Access Program.
4c3880bb027f159e801041b1021e88e8 Result
Cohort A accounted for 1588 patients with non-squamous NSCLC: 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 370 patients with squamous histology: 102 BoM+ (32%) and 251 BoM- (68%). In Cohort A, BoM+ had a significantly lower ORR (12% versus 34%; p < 0.0001), shorter PFS (2.0 versus 4.0 months, p < 0.0001) and shorter OS (7.4 versus 15.3 months, p <0.0001). In cohort B, BoM+ had significantly lower ORR (15% versus 22%; p < 0.04), shorter PFS (2.7 versus 5.4 months, p <0.0001) and shorter OS (5.0 versus 10.9 months, p <0.0001). Presence of BoM negatively affected outcome irrespective of PS (OS cohort A: PS-0 BoM+ 12.0 versus 20.9 months in PS-0 BoM-, p<0.0001; OS cohort B: PS-0 BoM+ 5.8 versus 16.4 months in PS-0 BoM-, p<0.0001). Multivariate analysis confirmed that presence of BoM independently associated with higher risk of death with HR 1.64 and HR 1.78, for Cohort A and B, respectively.
8eea62084ca7e541d918e823422bd82e Conclusion
Our results, the first assessing BoM in patients treated with immunotherapy, suggested that BoM predict lower efficacy of immunotherapy. BoM should be included as stratification factor in clinical trials.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.04-10 - Early Monitoring of Blood Biomarkers to Predict Nivolumab Efficacy in NSCLC Patients (ID 14101)
16:45 - 18:00 | Author(s): Hector Josè Soto Parra
- Abstract
Background
In the present study we investigated whether early dynamic changes of circulating free (cf) DNA levels as well as peripheral blood cells count could predict resistance to nivolumab in pre-treated patients with advanced non-small cell lung cancer (NSCLC).
a9ded1e5ce5d75814730bb4caaf49419 Method
From September 2015 to January 2018, 45 NSCLC patients receiving i.v nivolumab 3 mg/kg every two weeks were included within a translational study. All the patients underwent CT-scan every 6 cycles and responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Peripheral blood samples were obtained from the patients at baseline and at fourth cycle of therapy. The quantification of cfDNA (ng/µL plasma) was performed by qubit dsDNA HS assay and confirmed by qPCR evaluating a 115 bp fragment of ALU repeat. The median cfDNA level as well as the median neutrophil to lymphocyte ratio (NLR) value were calculated at the first and the fourth infusion of nivolumab. Time to progression (TTP) and overall survival (OS) were determined.
4c3880bb027f159e801041b1021e88e8 Result
Elevated baseline cfDNA level was associated with inferior OS (7.2 vs 13.5 months, p=0.04) while high pre-treatment NLR predicted inferior TTP (4.5 vs 9.7 months, p=0.006). Patients with increased median cfDNA level >20% at fourth cycle reported significantly worse OS and TTP (OS: 5.7 vs 14.2 months, p<0.001; TTP: 3.3 vs 10.2 months, p<0.001). Patients with increased median NLR >20% at fourth cycle of therapy showed significantly worse OS and TTP (OS: 8.7 vs 14.6 months, p=0.035; TTP: 5.2 vs 10.3 months, p=0.039). Patients with a simultaneous increase >20% of both cfDNA level and NLR value showed significant worse survival outcomes as compared to patients with only one increased parameter or not increase of both parameters (OS: 5.8 vs 11.1 vs 11.5 vs 15.4 months, p=0.012; TTP: 3.2 vs 6.5 vs 7.33 vs 11.9, p= 0.028).
8eea62084ca7e541d918e823422bd82e Conclusion
Early increase of both cfDNA level and NLR value is a marker of resistance to nivolumab and predict worse survival outcomes in pre-treated patients with advanced NSCLC, suggesting a potential role in the real time monitoring of immunotherapy efficacy.
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P2.04-11 - An IL-8/IFN-gammma/NLR Plasma Score to Predict Nivolumab Efficacy in Patients with NSCLC (ID 14139)
16:45 - 18:00 | Author(s): Hector Josè Soto Parra
- Abstract
Background
In the present study we investigated whether baseline plasma cytokines as well as neutrophil to lymphocyte ratio (NLR) could predict resistance to nivolumab in pre-treated patients with advanced non-small cell lung cancer (NSCLC).
a9ded1e5ce5d75814730bb4caaf49419 Method
From September 2015 to January 2018, 42 NSCLC patients receiving i.v. nivolumab 3 mg/kg every two weeks were included within a translational study. All the patients underwent CT-scan every 6 cycles and responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Peripheral blood samples were obtained from the patients at baseline. A panel of cytokines and chemokines (IL-6, IL-8, CXCL10, CX3CL1, CCL2, VEGF, and IFN- gamma) were quantified in plasma by Cytokine Bead Array and their association with OS and TTP was assessed by Adaptive Index Modeling multivariable analysis. NLR in blood cell counts was also assessed for potential association with clinical outcomes.
4c3880bb027f159e801041b1021e88e8 Result
An Index Score was identified clustering patients into 4 groups with progressively worsening TTP and OS. The score was composed by higher IL-8 and NLR (above the cut-offs of 10.76 pg/ml and 5.4, respectively) and lower IFN-gamma level (below cut-off of 11 pg/ml). Patients with score 0-1 (i.e. with none or 1 altered parameter; n= 17) displayed a median TTP of 11 months (95% IC= 5-NA) and median OS of 16 months (95% IC= 12-NA); in contrast, patients with score 2-3 (2 or 3 altered parameters; n=23) showed a median TTP of 3 months (95% IC= 2-5) and median OS of 5 months (95% IC= 2-8). The divergences among both TTP and OS Kaplan Meyers curves were statistically significant (P<0.0001). NLR alone showed instead either a borderline association with OS (p=0.048) and no ability to predict TTP (p=0.23).
8eea62084ca7e541d918e823422bd82e Conclusion
Baseline plasma levels of IL-8 and IFN-gamma potentiate the ability of NLR to predict resistance to nivolumab in pre-treated patients with advanced NSCLC. These data suggest that the systemic balance between neutrophil-related inflammation and lymphocyte anti-tumor immunity may condition response to immunotherapy in lung cancer.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.09 - Pathology (Not CME Accredited Session) (ID 958)
- 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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P2.09-21 - Women with Synchronous or Metachronous Lung and Ovarian Cancers: A Multi-Institutional Report (ID 12485)
16:45 - 18:00 | Author(s): Hector Josè Soto Parra
- Abstract
Background
In women, lung cancer (LC) and ovarian cancer (OC) are, respectively, the second and eighth malignancies for incidence in developed Countries. Despite increasing incidence and mortality of LC, association with OC is rare and no literature data are available on this topic yet. Our aim was to describe a series of patients with synchronous or metachronous LC and OC and to identify common clinical and pathological patterns.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrieved the medical charts of patients who referred to 30 European Oncological Institutes from 2008 to 2018. When patients with synchronous (up to 3 months of time interval in onset) or metachronous LC and OC were found, we collected detailed medical history, pathological features and clinical outcomes. Whenever available, formalin fixed paraffin embedded tumor tissue from both specimens was collected for centralized pathology revision with an immunohistochemical marker panel including TTF-1 and PAX-8. In ambiguous cases, a broader panel was performed (p40, CK-7, WT1, CA125, Calretinin, EMA, CEA, CgA, Vimentin, Napsin-A). Whenever tested, genetic alterations in LC and OC were also reported.
4c3880bb027f159e801041b1021e88e8 Result
As of April 2018, among 30 European Oncological Centers (Italy, France, Slovenia), 11 retrieved in their series patients with a history of LC and OC, for a total of 18 cases in the last 10 years. Paired histological specimens were available in 6 cases. One patient was excluded, since pathology revision revealed that lung lesions were metastases from serous OC. Thus, analyses were performed on 17 patients. In 10/17 cases (58.8%), LC and OC were metachronous and, in 6/10 cases, OC preceded LC diagnosis, with a median interval of 4.5 years. Median age at diagnosis of the first malignancy was 62 years, the majority of patients (64.7%) were never-smoker, 6 had cancer familial history. Interestingly, 4 patients (23.5%) reported also a third or fourth malignancy. After a median follow-up of 6.5 years, 10 patients are alive. Regarding histology, most of LC were adenocarcinoma (14/17, 82.3%). Molecular status was available in 9/14 cases: 4 had EGFR mutation, 1 B-RAF mutation and 2 ALK translocation. OC were mostly high-grade serous (83,3%). BRCA status was available in 6 patients: 2 mutated, 2 wild-type and 2 affected by variants of unknown significance (USV). Moreover, one synchronous case presented both BRCA-USV and B-RAF mutation.
8eea62084ca7e541d918e823422bd82e Conclusion
In our series, synchronous and metachronous LC and OC were often driven by genetic alterations. Further genetic analysis with next generation sequencing technology has already been planned.
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