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Benjamin Haaland
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FP05 - Mesothelioma, Thymoma and Other Thoracic Malignancies (ID 135)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP05.01 - Real-World Survival Outcomes of Patients with Malignant Pleural Mesothelioma by Choice of Second-line Therapy (ID 2718)
00:00 - 00:00 | Author(s): Benjamin Haaland
- Abstract
Introduction
Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a poor overall survival (OS). Disease biology, patient co-morbidities and performance status (PS), and a lack of biomarkers to guide therapeutic decision making all contribute to poor survival. There is limited data to guide choice of second-line therapy (2L) after progression of disease (POD) on first-line (1L) platinum-based combination chemotherapy. This study evaluates real-world survival outcomes of patients with MPM by physician’s choice of 2L single-agent chemotherapy versus immunotherapy.
Methods
The study included patients with MPM in the Flatiron Health nationwide electronic health record-derived de-identified database who initiated 2L therapy after POD on 1L platinum-based chemotherapy between May 2011 – July 2019, with follow-up through July 2019. Propensity weighting was performed to balance potential confounders, weight the Kaplan-Meier estimate of OS from initiation of 2L, and weight a Cox proportional hazard model on OS comparing immunotherapy versus single-agent chemotherapy. Propensity scores were constructed via logistic regression based on age, asbestos exposure, smoking history, region, race/ethnicity, PD-L1 status, histology, time to starting 2L therapy, serum creatinine, hemoglobin, absolute neutrophil, platelet, and white blood cell count, serum albumin, height, weight, 1L therapy, previous heart, kidney, neuropathy, and/or audiologic condition, and ECOG PS. An unweighted Cox proportional hazards model was fit adjusting for these baseline covariates and date of diagnosis.
Results
This study included 193 patients with MPM treated with single-agent chemotherapy (n=101) versus single-agent or combination immunotherapy (n=92) after POD on 1L platinum chemotherapy. Documented PD-L1 testing was limitedly available (n=38; 20%). Median age was similar between treatment groups. More patients with sarcomatoid histology and with ECOG PS 0 and 3 were treated with 2L immunotherapy than chemotherapy. Patients receiving single-agent chemotherapy were mostly diagnosed prior to 2016 (74%); only 15% of patients receiving immunotherapy were diagnosed by this time. The propensity score weighted analysis demonstrated an OS hazard ratio (HR) of 2L immunotherapy versus chemotherapy of 0.64 (p = 0.05; 95% CI: 0.41, 1.01). The unweighted analysis was consistent in estimating the HR to be 0.61 (p = 0.08, 95% CI = 0.35, 1.07).
Conclusion
This is the largest real-world evidence assessment of 2L therapy following platinum chemotherapy in patients with MPM. While non-significant, single or combination immunotherapy had a suggestive benefit on OS compared to single-agent chemotherapy. The benefit had as much as a 59% HR reduction of death and had no worse than a 1% increased HR on OS.
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OA09 - Mesothelioma from Pathogenesis to Therapy (ID 132)
- Event: WCLC 2020
- Type: Oral
- Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 15:30 - 16:30, Scientific Program Auditorium
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OA09.05 - Real-World Survival Outcomes of Patients with Malignant Pleural Mesothelioma by Physician’s Choice of First-line Platinum Chemotherapy (ID 2717)
15:30 - 16:30 | Author(s): Benjamin Haaland
- Abstract
- Presentation
Introduction
Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with poor overall survival (OS). Cisplatin is the preferred platinum chemotherapy backbone in national guidelines, and the only FDA-approved agent in combination with pemetrexed, due to observed survival benefits in clinical trials. Unfortunately, most patients with MPM are elderly, and many suffer from comorbidities or poor ECOG performance status (PS) which preclude cisplatin use. Carboplatin is routinely prescribed in practice given its tolerability. This study evaluates real-world survival outcomes of patients with MPM by first-line (1L) cisplatin versus carboplatin combination chemotherapy.
Methods
This study included patients with MPM in the Flatiron Health nationwide electronic health record-derived de-identified database who initiated therapy between January 2011 through July 2019 with follow-up through July 2019. OS was summarized by 1L platinum choice via Kaplan-Meier, and was compared in the context of a propensity weighted Cox proportional hazards model. Propensity scores were constructed via logistic regression based on age, asbestos exposure, smoking history, region, race/ethnicity, PD-L1-status, histology, weight, height, neuropathy, previous heart, kidney, and/or audiology condition, ECOG PS, diagnosis year, hemoglobin, neutrophil count, serum creatinine, and practice type (academic/community).
Results
This study included 735 patients with MPM, 68% had asbestos exposure, and 59% had epithelioid histology. More patients were treated with carboplatin (n=434) than cisplatin (n=301). Carboplatin treated patients were older (median age 77 versus 70 years) and had worse ECOG PS. Propensity weighting was performed to achieve balance of potential confounders (all SMDs < 0.1). The propensity weighted median OS for patients treated with 1L carboplatin was 12.45 months and cisplatin was 12.88 months, respectively. A propensity score weighted analysis demonstrated a hazard ratio (HR) of cisplatin relative to carboplatin of 1.09 (95% CI: 0.89 - 1.34) which is not statistically significant but places upper and lower bounds on the relative effect of the two therapies on OS.
Conclusion
To-date, this is the largest real-world cohort of patients with MPM. We found no statistically significant difference in OS by choice of 1L platinum chemotherapy. While more observations are required to determine which of the two treatments is superior for extending survival, we provide bounds in this cohort that cisplatin provides at most an 11% reduction on OS HR and up to a 34% increase on OS HR. This provides added context when choosing between the two agents, given what is known regarding carboplatin’s favorable tolerability and toxicity profile.
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P89 - Targeted Therapy - Clinically Focused - Translational (ID 266)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P89.05 - Management of Patients with EGFR and ALK-Mutated Advanced Non-Small Cell Lung Cancer Post-TKI Therapy – A Real-World Survival Analysis (ID 2719)
00:00 - 00:00 | Author(s): Benjamin Haaland
- Abstract
Introduction
Targeted therapy with tyrosine kinase inhibitors (TKIs) is the preferred first-line therapy for advanced non-small cell lung cancer (NSCLC) with actionable mutations. It is unknown which treatment strategy is most efficacious post-TKI progression. Studies have demonstrated minimal activity with single-agent immune checkpoint inhibitors (ICIs) and most combination chemoimmunotherapy (CIO) trials have excluded EGFR and ALK-mutated patients. We performed a real-world analysis to evaluate time to next treatment (TTNT) and overall survival (OS) for patients with EGFR and ALK-mutated NSCLC post-TKI progression.
Methods
The study included patients with EGFR and ALK-mutated NSCLC in the Flatiron Health nationwide electronic health record-derived de-identified database who initiated chemotherapy (C), CIO, immunotherapy (IO), or C with VEGF inhibition (CV) post-progression after initial treatment with one or more TKIs between 2011-2018, with follow-up through June 2019. We excluded patients with over 90 days between advanced diagnosis date and next visit to ensure patients were actively involved in care, and required initiation of post-TKI therapy at least 6 months before end of follow-up. TTNT and OS were compared for the four post-TKI therapy categories using Kaplan-Meier curves and multivariable Cox proportional hazards models. Models were adjusted for smoking (history/none), gender, age at post-TKI therapy, year of post-TKI therapy, time on TKI therapy, number of initial TKI therapies, and ECOG PS at time of TKI failure.
Results
This study included 480 patients with EGFR and 86 patients with ALK-mutated NSCLC. In adjusted analyses for TTNT, patients with EGFR-mutated tumors who received CIO and CV demonstrated improvements in TTNT with HRs of 0.46 (95% CI 0.30-0.70, p<0.001) and 0.74 (95% CI 0.57-0.96, p=0.02) relative to C, respectively. No statistically significant difference in TTNT between IO and C was detected. Results were similar among ALK-mutated patients, although not statistically significant. In adjusted analyses for TTNT, patients receiving CIO and CV had HRs of 0.40 (95% CI 0.15-1.06, p=0.06) and 0.52 (95% CI 0.25-1.06, p=0.07) relative to C, respectively. In adjusted analyses for OS, the only statistically significant finding was for CIO vs. C (HR 0.55, 95% CI 0.31-0.98, p=0.04) among patients with EGFR-mutated tumors.
Conclusion
Patients with EGFR and ALK-mutated advanced NSCLC demonstrate a TTNT benefit from combined CIO and C with VEGF inhibition post-TKI progression in the real-world. Ongoing and future clinical trials are needed to provide prospective evidence for the management of combination therapies in EGFR and ALK-mutated NSCLC patients who have exhausted TKI options.
