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Donald Morris
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MA11 - Biomarkers of IO Response (ID 912)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 203 BD
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MA11.04 - Discussant - MA 11.01, MA 11.02, MA 11.03 (ID 14619)
10:45 - 11:00 | Presenting Author(s): Donald Morris
- 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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P1.01-91 - A Phase I Study of Fixed Dose Vinorelbine and Escalating Doses of Ifosfamide in First-Line Advanced Non-Small Cell Lung Cancer (ID 14266)
16:45 - 18:00 | Author(s): Donald Morris
- Abstract
Background
Platinum doublet chemotherapy is generally the backbone treatment of advanced NSCLC (aNSCLC), although toxicity and limited benefit necessitated the need for investigation of alternatives. We examined vinorelbine and ifosfamide combination chemotherapy as a possible alternative in first-line aNSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
31 patients were enrolled and treated between January 2004 and July 2006. Vinorelbine (25 mg/m2) and escalating doses of ifosfamide were given on days 1 and 8 q21 days. The starting dose of ifosfamide was 2.0 g/m2. If ≤1/6 patients experienced dose-limiting toxicities (DLT) in cycle 1, the next cohort was recruited and given an additional 0.25 g/m2 of ifosfamide. If ³ 2/6 patients within a cohort experienced DLT, recruitment was halted, and previous cohort’s dose was determined to be ideal for phase II study. DLT were defined as grade 4 hematologic or grades 3 or 4 non-hematologic toxicities.
4c3880bb027f159e801041b1021e88e8 Result
The ideal phase II ifosfamide dose was determined to be 2.0 g/m2. Median PFS and OS were 5.5 and 9.2 months, respectively. The ORR was 12.9% and the 1-year OS was 21%, both lower than historical reports of platinum doublet efficacy and even vinorelbine monotherapy at 30 mg/m2. Six “excellent responders” were identified who survived between 20 and 45 months. DLT were experienced by 58% of patients. DLT were largely hematologic, but higher doses of ifosfamide produced non-hematologic toxicities.
8eea62084ca7e541d918e823422bd82e Conclusion
There was no significant evidence that vinorelbine and ifosfamide combination could provide an alternative to platinum doublet chemotherapy based on inferior efficacy and the high rate of DLT. The 6 “excellent responders” may be explained by chance or secondary to subsequent treatment with erlotinib while harbouring occult EGFR mutations. Further study may be relevant to examine synergy between vinorelbine or ifosfamide with modern targeted therapies.
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P3.03 - Biology (Not CME Accredited Session) (ID 969)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.03-21 - CXCR4 Overexpression is Associated with Poor Survival Outcome After Recurrence in Early Stage Non-Small Cell Lung Cancer Patients (ID 13659)
12:00 - 13:30 | Author(s): Donald Morris
- Abstract
Background
Overexpression of CXCR4 is associated with poor outcomes for patients with advanced non-small cell lung cancer (NSCLC). Studies suggest a gender specific difference in outcomes of stage IV NSCLC patients, with shorter survival in females with high expression of CXCR4. The current study evaluates the association between CXCR4 expression and gender, time to recurrence, and survival in early stage NSCLC patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patient characteristics, clinical variables and outcome data were obtained from the Glans-Look Lung Cancer database for stage I-III NSCLC patients diagnosed between 2003-2006 at the Tom Baker Cancer Centre. Tissue microarrays were created from surgical or biopsy specimens, and CXCR4 expression was evaluated using quantitative fluorescent immunohistochemistry. CXCR4 expression and outcome data were analyzed using a Cox proportional hazards and multi-state model.
4c3880bb027f159e801041b1021e88e8 Result
230 patients with stage I-III NSCLC were identified, and 181 patients had corresponding tissue for CXCR4 analysis. Early stage NSCLC patients with CXCR4 overexpression had worse overall survival compared to those with low CXCR4 expression (p<0.05). No gender specific difference was observed. Time to recurrence did not correlate with CXCR4 expression, and there was no association with the site of recurrence (local versus distant). However, high CXCR4 expression was associated with increased risk of death after recurrence (p<0.05).
8eea62084ca7e541d918e823422bd82e Conclusion
Early stage lung cancer patients with high CXCR4 expression have worse survival outcomes, particularly after recurrence of disease. The role of CXCR4 as a prognostic marker in NSCLC patients who have recurred should be further elucidated.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.13-28 - Heterogeneity, Prevalence and Prognostic Significance of PDL1 Expression in Early Resected NSCLC (ID 14335)
12:00 - 13:30 | Author(s): Donald Morris
- Abstract
Background
The interaction between the programmed death protein-1 receptor (PD1) and its membrane-bound ligand (PDL1) is one mechanism by which tumor cells evade the immune system. Cancer immunotherapies target this interaction by blocking the function of either protein, allowing for T-cell activation and destruction of the tumor. Because PDL1 expression in tumor is used to identify patients who might benefit from immune-modulating treatment, its detection plays a key role in clinical recommendations. Our objectives are to assess the prevalence of PDL1 expression in early stage non-small cell lung cancer (NSCLC) patients, determine its association with clinical outcomes using the Glans-Look Research (GLR) database (Calgary, AB), and validate these findings using a cohort from the Manitoba Tumor Bank (MBTB).
a9ded1e5ce5d75814730bb4caaf49419 Method
A tissue microarray (TMA) was built using pre-treatment resected and biopsy tissue samples from 459 GLR database patients with early stage NSCLC, diagnosed between 2003 and 2010. Cell lines expressing varying levels of PDL1 were generated, embedded into HistoGel™ and co-mounted onto the GLR and MBTB arrays. Fluorescence immunohistochemistry was performed using anti-PDL1 E1L3N (Cell Signaling Technology), and PDL1 expression was evaluated as percent-positive and intensity scores in the cytoplasmic compartment of tumor and stromal cells using HALO™ automated image analysis software. Cell line PDL1 intensity scores served as on-slide reference standards to normalize PDL1 expression in patient specimens using R Programming software. PDL1-percent-positive tumor scores were generated to assess the cut-points of ≥50%(“PDL1-strong”), ≥1%-to-49%(“PDL1-weak”), and <1%(“PDL1-negative”), indicated by the FDA-approved companion diagnostic anti-PDL1 22C3 (Dako) for pembrolizumab. Clinicopathological outcomes were analyzed, and overall survival was assessed using the Kaplan-Meier method and compared using the log-rank test.
4c3880bb027f159e801041b1021e88e8 Result
Preliminary analyses indicate PDL1-weak/negative GLR patients with adenocarcinoma experienced higher median OS (3.50yrs) compared to PDL1-strong patients (1.91yrs) (p=0.0043). This trend was not significant over all histologies, or when using mean scores. The opposite trend was found with the MBTB cohort (2.52yrs vs. 1.76yrs OS, PDL1-strong vs. PDL1-weak/negative maximum scores, p=0.0410).
8eea62084ca7e541d918e823422bd82e Conclusion
Variations across datasets illustrate the difficulty in harmonizing PDL1 testing. Heterogeneity of protein expression, TMA sampling error, and differences between study cohorts can translate into variable correlations between PDL1-positivity and survival estimates. Increased survivorship in GLR adenocarcinoma patients with PDL1-weak/negative staining could challenge the notion of using PDL1 as a prognostic biomarker. Comparisons between the E1L3N and 22C3 anti-PDL1 assays will be performed, E1L3N percent-positive cut-points will be refined according to the lowest intensity-based statistical p-value, and further outcome findings will be presented and discussed.
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