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J. Molina
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MA04 - HER2, P53, KRAS and Other Targets in Advanced NSCLC (ID 380)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
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MA04.08 - Discussant for MA04.05, MA04.06, MA04.07 (ID 7078)
16:48 - 17:00 | Author(s): J. Molina
- Abstract
- Presentation
Abstract not provided
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OA13 - Immunotherapy in Malignant Pleural Mesothelioma: Current Status of Trials and New Approaches (ID 392)
- Event: WCLC 2016
- Type: Oral Session
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
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OA13.07 - Intrapleural Modified Vaccine Strain Measles Virus Therapy for Patients with Malignant Pleural Mesothelioma (ID 5655)
15:25 - 15:35 | Author(s): J. Molina
- Abstract
- Presentation
Background:
Malignant pleural mesothelioma (MM) remains an almost universally fatal disease with limited treatment options. Preclinical models indicate the preferential oncolytic activity of the modified vaccine strain measles virus carrying the gene for the human sodium-iodine symporter (NIS) – MV-NIS. Intraperitoneal and intravenous administration of MV-NIS was recently found to be potentially effective in patients with refractory ovarian cancer and multiple myeloma. However, whether MV-NIS is directly oncolytic or triggers an anti-tumor immune response remains unclear.
Methods:
We conducted a phase I dose escalation study with 3+3 design and ongoing maximal tolerated dose (MTD) expansion cohort. MV-NIS was administered as first or second line therapy via a tunneled intrapleural catheter to patients with MM. MV-NIS dose ranged from 10[8] TICID~50~ to 9 x 10[9] TICID~50~. In the absence of dose limiting toxicity and disease progression, patients received up to 6 cycles of MV-NIS therapy (Phase I). Currently additional patients are being randomized between a single and multiple cycles. MV-NIS infection and replication are monitored by Iodine[123] SPECT/CT (Phase I only) as well as by RT-PCR and/or plaque-assay. Anti-tumor immunity is monitored in the blood and pleural fluid and patients are followed clinically by chest CT using the modified RECIST criteria.
Results:
Twelve patients (3/dose level) received MV-NIS therapy. There were no dose limiting adverse events and therapy was well tolerated. The best therapeutic response was stable disease, which was achieved at 1 month by 8/12 evaluable patients (67%). Median overall survival was 449 days (95%CI: 221, 484) (~15 months) (4/12 patients remain alive), and median progression free survival was 63 days (95% CI: 33, 174) (~2 months). MV infection and replication were detectable by RT-PCR and plaque assay in the pleural fluid between 24-72 hours after treatment. I[123] SPECT-CT demonstrated only marginal viral gene expression in a single patient treated with the highest dose level. MV-NIS therapy effectively boosted pre-existing anti-MV neutralizing antibody responses in the plasma and pleural fluid of most patients. We observed a transient inflammatory response in the pleural space after MV-NIS administration. In addition, induction or boosting of anti-tumor antibody responses was observed.
Conclusion:
The intrapleural administration of MV-NIS is safe, resulted in stable disease for 67% of patients and may be associated with favorable overall survival in MM. While there was only transient infection and viral replication, we observed the induction of anti-tumor immune responses supportive of potential long-term therapeutic impact. The study continues with the MTD expansion cohort.
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P1.05 - Poster Session with Presenters Present (ID 457)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.05-064 - Global Practice Patterns of Multifocal Lung Cancer (ID 4398)
14:30 - 14:30 | Author(s): J. Molina
- Abstract
Background:
Multifocal lung cancer (MFLC) is a clinical scenario that is more frequently diagnosed with the increased utilization of computed tomography of the chest. The management of MFLC is limited by the difficulties in accurately staging a patient and understanding whether lesions represent separate primaries or metastatic disease. We sought to understand the global practice patterns of MFLC.
Methods:
A questionnaire was developed and sent to members of the International Association for the Study of Lung Cancer through REDCap electronic data capture tools to assess how a hypothetical patient with synchronous MFLC would be evaluated and treated. Responses were compared by specialty using the χ[2] test.
Results:
We received 221 responses from multiple specialists (74 Thoracic Surgeons, 68 Medical Oncologists, 32 Pulmonologists, 22 Radiation Oncologists and 25 others) primarily from Europe (n=76) and North America (n=62). Over 87 respondents reported 20 or more years of experience in the field. Most respondents recommended surgery (n=140, 63%), but many others did not (n=39, 18%) or were uncertain (42, 19%). Surgeons (n=60/74, 81%) were significantly more likely to recommend surgery than medical oncologists (n=37/68, 54%), pulmonologists (n=21/32, 66%) or radiation oncologists (n=10/22, 45%; p=0.01). Lobectomy of the primarily involved lobe (n=42, 30%) and various combinations of segmentectomies (n=48, 34%) were the most commonly recommended surgical approaches. Of those who recommended surgery, most would obtain a PET/CT to rule out distant metastasis (n=135, 97%) and an MRI to rule out brain metastases (n=76, 55%) but in the absence of radiographic lymph node involvement most would not stage the mediastinum by bronchoscopy or mediastinoscopy prior to resection (n=90, 65%). Many preferred obtaining multiple biopsies of separate lesions (n=139, 63%) and genetic testing of these lesions (n=146, 66%) to assess their histologic and genetic agreement. In the case that surgery was not offered or declined, more respondents recommended radiation (n=114, 52%) than those who did not (n=50, 23%) or were uncertain (56, 26%). Similarly, in the absence of surgery or radiotherapy, slightly more respondents recommended systemic chemotherapy (n=83, 38%) than those who did not (n=79, 36%) or those who were uncertain (n=59, 27%).
Conclusion:
Although most respondents favored surgery when feasible for MFLC, many were uncertain as to the optimal approach for this disease. Optimal management of MFLC requires greater evidence from studies which is currently lacking, and current strategies are strongly influenced by specialty bias.
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 2
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-036 - Large Cell Neuroendocrine Carcinoma of the Lung: The Mayo Clinic Experience (ID 4925)
14:30 - 14:30 | Author(s): J. Molina
- Abstract
Background:
Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon, high-grade neuroendocrine tumor sharing several features with small-cell lung carcinoma (SCLC). LCNEC is considered aggressive, and the optimal treatment strategy and chemotherapy regimen remain undefined.
Methods:
We retrospectively evaluated a LCNEC patient cohort established from 1997 to 2015 at Mayo Clinic (Minnesota). A diagnosis of LCNEC was made when all WHO classification criteria were present in the tumor section examined. Clinical characteristics, treatment and outcomes were analyzed. Available radiology assessment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Results:
The study included 55 LCNEC patients. Median age at diagnosis was 63 years (range: 38-88); two thirds were men; and majority were smokers (94%). Clinical staging was I, II, III or IV in 52.8%, 9.1%, 14.5%, and 23.6% of cases, respectively. Forty-six percent of stage IV patients presented with brain metastases at time of diagnosis (n=6/13) and 18% (n=7/38) developed brain recurrence in the follow up period. Thirty-nine (71%) patients had surgery and 9 (16%) patients received adjuvant platinum-based chemotherapy. Sixty-five percent of patients with complete resection experienced disease recurrence with 80% recurring within 2 years of resection. Treatment data for first-line palliative chemotherapy were available on 23 patients: 10 received platinum/etoposide and 13 received other regimens. In 19 patients with available imaging; the overall response rate was 52.6% (95% CI, 31.7-72.7) and there was no difference in ORR between platinum/etoposide (ORR=55.6%) or platinum plus other agents (paclitaxel or pemetrexed; ORR=55.6%). The median survival time was 26.3 months (95%CI; 18.6-33.9); the 1-, 2-, 3- and 5-year overall survival rates (OS) were 75%, 53%, 36%, and 30%, respectively. Patients who received platinum/etoposide demonstrated longer median time to progression (TTP), and median OS than those who received ‘other’ regimens (14.7 months vs. 7.1 months; p value 0.07, and 28.2 months vs. 21.1 months; p value 0.22, respectively); the differences did not reach conventional statistical significance, likely due to the small sample size. Rigorous pathologic confirmation and genomic analysis are ongoing.
Conclusion:
LCNEC is associated with a poor prognosis and high recurrence rates after surgery. Advanced LCNEC patients are at high risk for brain metastases, therefore, routine brain imaging surveillance during follow-up may be beneficial. The chemotherapeutic responsiveness of LCNEC patients was intermediate between that of NSCLC and SCLC patients. Future prospective, multicenter, clinical trials are needed to determine the best chemotherapy regimen for these rare tumors.
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P1.07-045 - Characteristics of Exceptional Long Term Survivors in Extensive Stage Small Cell Lung Cancer (ID 5527)
14:30 - 14:30 | Author(s): J. Molina
- Abstract
Background:
Small cell lung cancer (SCLC) remains a frustrating disease to all parties involved. Most patients present with extensive stage disease (ED), with a median survival of 8 to 13 months (Expected). The aim of this study is to present data on survivors who lived beyond 3 years after a diagnosis of ED-SCLC (Exceptional) in order to uncover favorable factors for better patient management and clinical outcomes.
Methods:
We retrospectively evaluated the SCLC patient cohort diagnosed and followed from 1997 to 2015 at Mayo Clinic (Minnesota), and searched for Exceptional survivors with matched Expected survivors who had passed away within 12 months of diagnosis on age and year of diagnosis. Patient characteristics, treatments, and outcomes were compared between the two groups.
Results:
To date, we identified 36 Exceptional and 144 Expected ED-SCLC patients. Women and an Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) 0-1 were higher in Exceptional than in Expected group (61.8% vs 36.1%, p<0.01; 97.2% vs 77.6%, p<0.01; respectively). Smoking history, comorbidities (COPD, prior cancers or paraneoplastic syndrome), and T or N stage did not differ significantly. The top two metastatic sites in Exceptional group were brain (26.7%) and distant lymph nodes (20.0%), and in Expected were liver (28.3%) and bone (22.5%). Use of chemotherapy and the mean cycle number were higher in the Exceptional than the Expected group (100.0% vs 80.0%, p<0.01; 5.0 vs 3.6, p<0.01; respectively), with the main regimen being platinum/etoposide. However, carboplatin was used more frequently than cisplatin in Expected group (all patients, p=0.02; ECOG 0-1 patients, p=0.05). The overall response rate of chemotherapy was significantly higher in exceptional group (91.4% vs 56.7%, p<0.01). Thoracic radiotherapy and prophylactic cranial irradiation (PCI) in Exceptional were also higher than in Expected group (58.3% vs 17.4%; p<0.01, 19.4% vs 6.9%; p=0.03). Multivariate analysis is underway. In Exceptional group, median overall survival was 5.4 years (95% CI 3.7-6.8); 9 (25%) patients were still alive. Twelve (33%) patients had disease recurrence or progression with the median progression free survival 1.2 (95% CI 0.7-2.0) years. The most common recurrent site was brain. Three patients had secondary malignancy, 2 being a non-small cell lung cancer.
Conclusion:
Although the chance of curing ED-SCLC is small, long-term survival can be achieved. This study supports the importance of good performance status and the achievement of a response to cisplatin-based chemotherapy on long-term survival. Addition of thoracic radiotherapy and PCI are beneficial in prolong life of ED-SCLC patients.
