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Joseph Treat
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OA09 - Lung Cancer: A Preventable Disease? (ID 134)
- Event: WCLC 2019
- Type: Oral Session
- Track: Prevention and Tobacco Control
- Presentations: 1
- Now Available
- Moderators:Bienvenido Barreiro, Carolyn Dresler
- Coordinates: 9/09/2019, 11:00 - 12:30, Melbourne (1991)
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OA09.05 - Lung Cancer as a Second Primary Malignancy Among Women with Breast Cancer: The Role of Hormone Replacement and Smoking (Now Available) (ID 1430)
11:00 - 12:30 | Author(s): Joseph Treat
- Abstract
- Presentation
Background
Women are more susceptible to tobacco-related lung tumorigenesis, and makeup a disproportionate number of lung cancer cases among never-smokers. This gender bias has prompted an investigation of the role of hormonal factors in lung tumorigenesis. Most breast cancers are hormone-mediated. Likewise, emerging evidence suggests that estrogen metabolites may contribute to lung tumorigenesis. Patients with a dual diagnosis of a primary lung and a primary breast cancer are of interest, as their development may be hormonally-driven. This research studies this by examining a cohort of women with breast cancer to assess hormone use, its interaction with cigarette smoking, and the risk of developing lung cancer as a second primary malignancy.
Method
A secondary analysis of the Women’s Health Initiative (WHI) clinical trial and observational study cohorts was performed and was restricted to patients with a diagnosis of breast cancer. Women 50 to 79 years of age were enrolled from October 1, 1993 to December 31, 1998, and follow-up ended on September 30, 2010. A total of 9,593 incident breast cancers were diagnosed and of these women, 120 had a subsequent primary lung cancer. Multivariable logistic regression was performed to test associations between hormone use, smoking history, reproductive factors, and the risk for lung cancer as a second primary malignancy. All predictor variables were assessed at enrollment/baseline.
Result
While current hormone use at baseline was not independently associated with risk for developing lung cancer as a second primary, current smoking at baseline was an independent predictor of risk (OR: 3.2, p=0.001). Among women with breast cancer who were both current smokers and current users of hormone replacement, the risk of lung cancer was significantly increased (OR: 7.7, p=0.024) compared to women who were not current smokers and not current users of replacement hormones.
Conclusion
Hormone replacement may increase the risk for lung cancer as a second primary malignancy in smoking breast cancer patients. Although hormone therapy is no longer preferable, this finding suggests an interplay between estrogen exposure and smoking, which may contribute to the greater susceptibility of women for smoking-related lung cancer. These data are consistent with results from preclinical studies by this group that indicate that smoking induces cytochrome P450 1B1, leading to higher levels of the putative carcinogenic estrogen metabolite 4-hydroxyestrogen in lung tissue. Smoking increased the risk of a second lung malignancy in this study, independent of hormone use, and tobacco cessation should be encouraged for all patients with breast cancer.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-109 - Phase II Trial of Pemetrexed/Carboplatin/Bevacizumab +/- Atezolizumab in NSCLC Patients That Are EGFR Mutated or Never Smoked (Now Available) (ID 1456)
09:45 - 18:00 | Author(s): Joseph Treat
- Abstract
Background
Patients with advanced NSCLC who harbor an EGFR mutation or are never smokers do not benefit from single-agent immunotherapy. Retrospective subgroup analyses from recent phase III trials suggest that immunotherapy-chemotherapy +/- VEGF inhibition may overcome the resistance to immunotherapy seen in these patients, though further prospective research is needed and no checkpoint inhibitor to date is approved in the first-line for EGFR patients after TKI failure. This trial will exclusively examine a population of patients with stage IV non-squamous disease who either have an EGFR exon 19 or 21 mutation or are never smoker wild-types to determine whether the PD-L1 inhibitor atezolizumab in combination with pemetrexed/carboplatin and bevacizumab can improve outcomes.
Method
This is a phase II double-arm, multi-center, open-label trial to assess pemetrexed/carboplatin and bevacizumab +/- atezolizumab in 117 subjects with stage IV non-squamous NSCLC. Randomization will be 2:1 with twice the number in the + atezolizumab arm, and randomization will be stratified by EGFR mutation status (i.e. EGFR exon 19 or 21 vs. never smoker wild-type) to ensure equal distribution in each arm. Never smoker wild-type is defined as smoking < 100 cigarettes in a lifetime and without any EGFR mutation or ALK or ROS1 rearrangement. Patients with EGFR exon 19 or 21 mutations must have progression or intolerance of treatment with prior TKI therapy. All patients must be chemotherapy, immunotherapy, and VEGF inhibitor therapy naïve. Primary endpoint will be progression-free survival (PFS). Secondary endpoints will include overall survival (OS), overall response rate, duration to response, and time to response. Primary objective is to compare PFS between arms. Secondary objectives include a safety analysis in all treated subjects, and comparisons of PFS and OS between arms for the subset of patients with tumors with EGFR exon 19 or 21 mutations. Correlative studies will include evaluation of biomarkers of the signaling network and tumor microenvironment, and characterizing the potential contribution of estrogen metabolites. Enrollment for this trial will open in August of this year and accrual will continue for 31 months.
Result
Section not applicable - Trial in progress
Conclusion
Section not applicable - Trial in progress
