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Thierry M Jahan
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-58 - A Phase II Study to Evaluate Neoadjuvant Osimertinib for Surgically Resectable, EGFR-Mutant Non-Small Cell Lung Cancer (ID 580)
09:45 - 18:00 | Author(s): Thierry M Jahan
- Abstract
Background
The third-generation Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is well-tolerated and effective for first-line treatment of metastatic EGFR-mutant non-small cell lung cancer (NSCLC). The efficacy of osimertinib in the treatment of early stage EGFR-mutant NSCLC, however, is unknown, and cytotoxic chemotherapy is considered the standard of care when systemic therapy is necessary for these patients. Neoadjuvant chemotherapy is an established therapeutic modality in locally-advanced NSCLC, in which a major pathologic response is associated with improved survival. Neoadjuvant use of targeted therapies in oncogene-driven NSCLC may offer the dual advantages of increased response rates and of more favorable toxicity profiles compared to cytotoxic chemotherapy, and also provides the opportunity to identify mechanisms underlying tumor cell persistence despite optimal oncogene-targeted therapy.
Method
This ongoing phase II, multi-institution study aims to enroll 27 patients with surgically resectable stage I-IIIA EGFR-mutant NSCLC. Patients are treated with one to two months of osimertinib 80 mg orally daily followed by surgical resection. The primary endpoint is major pathologic response (mPR) rate, defined as less than 10% residual viable tumor at surgical resection. Secondary endpoints include safety assessment, unanticipated delays to surgery, surgical complication rate, pathological complete response rate (pCR), unconfirmed objective response rate (ORR), rate of lymph node downstaging, disease-free survival, and overall survival. Tumor biopsies are obtained prior to osimertinib treatment in order to permit comparative correlative studies between pre- and post-osimertinib treated tumors. This includes genomic and transcriptomic analyses, evaluation of tumor immune cell infiltrates, and development of patient-derived model systems for functional validation studies.
Result
As of March 2019, five patients with EGFR-mutant NSCLC (2 stage IIIA, 1 stage IB, 2 Stage IA) have been enrolled and treated with osimertinib for an average of 56 days prior to surgical resection. Restaging imaging prior to surgical resection demonstrated an unconfirmed radiographic partial response in three patients (60% ORR) and stable disease in two patients (100% disease control rate). The mPR rate is 20% (1 of 5). No pCR’s were observed. One patient demonstrated lymph node downstaging from N2 to N0. Treatment was well-tolerated without SAEs and all patients proceeded to surgical resection without unscheduled delay or surgical complications. Genomic and immunophenotyping analyses are underway and will be reported.
Conclusion
Preliminary data from this phase II study indicates that neoadjuvant osimertinib treatment in surgically-resectable, EGFR-mutant NSCLC is well-tolerated and can induce pathological responses and downstaging of disease prior to surgery.
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P2.06 - Mesothelioma (ID 170)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.06-09 - Drop the Scalpel: Long-Term Survival in Mesothelioma Without Extrapleural Pneumonectomy or Pleurectomy Decortication (ID 2610)
10:15 - 18:15 | Author(s): Thierry M Jahan
- Abstract
Background
Survival times following multimodality treatment with extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) for malignant pleural mesothelioma (MPM) are poor with a need to identify factors that predict long-term survival.
Method
A retrospective single-institution review was performed on all patients who underwent EEP or P/D for histologically confirmed MPM between 1996 and 2015. Patients who underwent a diagnostic biopsy or limited tumor excision were included for survival comparison in a non-operative group (NO). Clinical characteristics, perioperative outcomes, stage, nodal disease, R1 versus R2 resection, treatment modalities, and survival data were collected. The top decile of patients with longest overall survival were studied in subgroup analysis as “long-term survivors.”
Result
A total of 206 patients with MPM underwent any type of operations with a median survival time of 13 months (range, 0-134 months) and a 3-year and 5-year survival rates of 15.9% and 8.1% respectively among all patients. Median survival times following EPP (n=28), P/D (n=102) and NO (n=76) were 14 months, 13 months, and 11 months respectively. Better survival was observed in patients with epithelial histology (16 months, n=146) than biphasic histology (7 months, n=28) or sarcomatoid histology (5 months, n=27) (logrank p<.001). Patients with epithelial histology had the greatest median survival times, EPP (29 months, n=23), P/D (16 months, n=77) and NO (16 months, n=46). Three-year and 5-year overall survival rates among patients with epithelial histology were 34.7%, 14.9% after EPP, 16.7, 10.4% after PD and 25.9%, 8.1% after NO, with the patients in the NO group presenting with the most advanced disease. The top decile of long-term survivors all had epitheliod histology and were treated with a variety of chemotherapy regimens leading to a median survival of 64 months with a mean of 71 months. Patients with disease too advanced for surgical resection in the NO group were equally likely to become long-term survivors (9.2%, median survival 57 months) compared with patients who underwent major surgical resection like EPP or P/D (10.0%, median survival 72 months).
Conclusion
In this non-randomized retrospective review, patients with MPM too advanced for EPP or PD, who instead underwent palliative limited operations as part of a multimodality treatment regimen had long-term survival rates of approximately 10% that were equivalent to rates of long-term survival following major resections like EPP or P/D. Long-term survival is mesothelioma is therefore more likely determined by outside factors such as disease biology and pace of tumor growth than it is major surgical resection.
