e21213 Background: Lung cancer is the leading cause of death in males and females in the United States. Approximately 85% of all cases are classified as non-small cell lung cancer (NSCLC) with majority diagnosed at an advanced stage. Unfortunately, response to traditional chemotherapy (ChT) has been poor with a five-year survival rate of 6% in metastatic NSCLC. Immune checkpoint inhibitors (ICI) have changed the therapeutic landscape for advanced NSCLC and are being utilized alone or in combination with ChT as the standard first-line therapy. With widespread use of ICIs, immune-related adverse events (irAE) are commonly seen and in some studies their occurrence correlates with improved outcomes. The aim of our study was to evaluate whether development of irAEs has an impact on survival in NSCLC. Methods: We performed a retrospective analysis on stage IV NSCLC patients treated with ChT, ChT plus ICI, or ICI monotherapy from December 2016 to December 2019. Univariable and multivariable analyses identified characteristics predictive of progression-free survival (PFS) and overall survival (OS). OS was calculated using Kaplan Meier curves. Log-rank statistics were used to assess statistical significance between groups. Multivariable logistic regression was performed to identify predictors of survival. Results: 193 patients were evaluated out of which 92 (47.2%) received ChT plus pembrolizumab, 69 (35.4%) received pembrolizumab alone and 32 (16.4%) received ChT alone. 130 patients were found to have no irAEs compared to 57 patients who were noted to have any grade of irAE. The median PFS was 17.4 months (irAE group) vs. 8.5 months (non-irAE group) with hazard ratio (HR) of 0.58 (95% CI: 0.41 to 0.80, p = 0.001). The median OS was 29.4 months (irAE group) vs. 14.4 months (non-irAE group) with HR of 0.56 (95% CI: 0.39 to 0.82, p = 0.0026). A multivariate analysis was performed for age, gender, ECOG performance status, insurance status, BMI, PDL1 status and smoking history, amongst other variables. Worse survival outcomes were noted with an ECOG performance status ≥ 2, no history of smoking, and involvement of palliative care. Multivariable logistic regression analysis showed that PDL-1 expression > 50% was the only predictor of developing an irAE. Of note, receipt of ChT in combination with pembrolizumab compared to pembrolizumab alone did not predict for development of irAE. Conclusions: Development of irAEs was associated with doubling of PFS and OS, regardless of whether the ICI was administered alone or in combination with ChT. The differences were statistically significant regardless of age, gender, race, BMI, insurance status or performance status. Our study highlights the correlation between development of irAEs and improved survival outcomes in advanced NSCLC patients treated with ICIs.
Background Pheochromocytomas are a subset of paragangliomas, which are a rare group of neural crest cell-derived tumors. Malignant cases of both pheochromocytomas and paragangliomas are even rarer, and currently there is no standard of care. This case report details the use of off-label immunotherapy and its efficacy in the management of the aforementioned tumor. Case presentation Herein is presented a case of a 60-year-old Caucasian female with a rare malignant pheochromocytoma. The tumor was determined to be unresectable because of involvement of surrounding organs. Radiation therapy was also not a viable option because of concerns over appreciable toxicity in relation to mass size. As there is no standard of care for malignant cases, the patient was started on chemotherapeutic agents but was soon shown to be intolerant to this treatment. As she was ineligible for several clinical trials, the patient was started on the off-label immunotherapeutic agents nivolumab and ipilimumab. Immunotherapy use resulted in decreased tumor size, improved quality of life, and reconsideration for radiation therapy. Conclusions The use of immunotherapy in pheochromocytoma in this patient clearly demonstrated substantial benefit, as she was able to be reconsidered for radiation therapy. Not only has the patient been tolerant of this treatment, but she has exhibited progression-free survival of over 20 months. As there is no current standard treatment for malignant pheochromocytomas, the success of its use in this patient lends support to the ongoing clinical trials regarding the use of immunotherapy in rare tumors, including pheochromocytomas.
e16247 Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal solid tumors, predicted to become the second leading cause of cancer related death in some regions of the world. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Only about 20% of the cases are diagnosed early enough to undergo surgical resection leading to complete remission. While chemotherapy has an established role in the setting of metastatic disease, utilizing it in the neo-adjuvant setting has been adopted by most institutes for resectable/ borderline resectable cases. Ongoing trials are exploring the use of different regimens in the neo-adjuvant setting. The aim of our study was to identify patients with resectable/borderline resectable PDAC undergoing neoadjuvant chemotherapy and differences in surgical outcome based on the regimen received i.e gemcitabine/ nab-Paclitaxel vs FOLFIRINOX. Methods: A retrospective review was conducted of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Summary statistics were presented using percentages for categorical variables and medians with interquartile ranges for continuous variables. Results: Out of 121 patients who received and completed treatment in our institution, 30 underwent neoadjuvant chemotherapy treatment followed by surgical intervention. 21 (70%) patients were found to be borderline resectable, 8 (27%) patients were resectable and 1 patient had locally advanced PDAC. 16 (53%) patients received FOLFIRINOX compared to 13 (43%) patients received gem/nab-paclitaxel. Among patients who received neoadjuvant FOLFIRINOX, 5 out of 16 (31%) patients had moderate to significant treatment response at the time of surgery compared to 7 out of 13 (54%) patients who received gemcitabine/nab-paclitaxel. Conclusions: Our study revealed no significant difference (p=0.21) between the patients who received neoadjuvant gemcitabine/nab-paclitaxel vs FOLFIRINOX in terms of treatment response assessed pathologically at the time surgical resection. We recognize the limitations of our study in terms of it being a retrospective analysis with a small sample size and therefore further prospective and randomized controlled trials are needed to determine the most suitable and effective regimen in the neoadjuvant setting for resectable/borderline resectable PDAC patients. Response to treatment among different chemotherapy groups.[Table: see text]
e18610 Background: Early stage pancreatic ductal adenocarcinoma (PDAC) account for up to 30% of newly diagnosed patients. Until recently, the mainstay of treatment remained curative-intent surgery followed by adjuvant chemotherapy. More recently, the incorporation of neoadjuvant therapy (NAT) has demonstrated clinical benefit. The two commonly used regimens are 5-Fluorouracil, Leucovorin, Oxaliplatin and Irinotecan (FOLFIRINOX), or Gemcitabine and nab-Paclitaxel. Limited data is available to differentiate outcomes between the 2 common NAT regimens. We conducted a retrospective review to assess the rates of disease recurrence and progression after neoadjuvant chemotherapy and to identify any associations that may predict early recurrence. Methods: A retrospective review was conducted of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Disease recurrence or progression was assessed radiologically, and time to progression was calculated as time (months) since diagnosis to evidence of radiological progression. Results: Out of 171 patients reviewed, 56 were deemed resectable or borderline resectable and underwent curative-intent surgery and were included in the analysis. Median age was 68, and 12 (41%) were male. Majority of the patients were white (90%). 29 (52%) patients received neoadjuvant chemotherapy: 16 (55%) received FOLFIRINOX, 12 (41%) received Gemcitabine with nab-Paclitaxel, and 1 received another regimen. 9 patients out of 16 (56%) that received FOLFIRINOX progressed, and 5 out of 12 patients (42%) who received Gemcitabine with nab-Paclitaxel progressed. Patterns of progression in those that received FOLFIRINOX: 1 (11%) within 6 months, 4 (44%) between 6-12 months, and 4 (44%) after 12 months. Of those that received Gemcitabine with nab-Paclitaxel, 2 (40%) progressed within 6 months, 1 (20%) progressed between 6-12 months, and 2 (40%) progressed after 12 months. On multivariate analysis, no association was identified to predict progression. Conclusions: There was no significant difference in disease progression rates among patients that received neoadjuvant FOLFIRINOX versus Gemcitabine and nab-Paclitaxel (42% vs. 56%; p = 0.46). No predictive associations were identified in patients with disease recurrence. Study limitations include a low sample size and retrospective analysis. Further, larger scale studies are warranted to better assess the difference in rates of progression after neoadjuvant FOLFIRINOX versus Gemcitabine and nab-Paclitaxel.[Table: see text]
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