Brian Hunis

Immunotherapeutic Agents in Non-small-cell Lung Cancer Finally Coming to the Front Lines

Non-small-cell lung cancer usually carries a dismal prognosis. Novel treatment approaches are clearly warranted. Immunotherapy has emerged as a promising area of research developing agents that manipulate the immune system to induce antitumor responses while avoiding major toxicity. New vaccines and checkpoint inhibitors are currently undergoing investigation in phase II and phase III clinical trials. In advanced non-small-cell lung cancer (NSCLC), belagenpumatucel-L, an allogeneic cell vaccine directed against transforming growth factor β in the tumor microenvironment, knocks down the immune suppression caused by the tumor and has demonstrated a dose- and time-dependent efficacy in some subgroups of patients. L-BLP25 and TG4010 are both antigenic vaccines that target mucin 1, whose encoding proto-oncogene is commonly mutated in solid tumors. The L-BLP25 vaccine achieved a significant improvement in overall survival in the subgroup of patients with stage IIIB NSCLC treated with chemoradiotherapy. TG4010 vaccination resulted in better progression-free survival when added to cisplatin–gemcitabine chemotherapy. These results are being addressed in the currently ongoing phase III TIME trial. In the adjuvant setting, MAGE-A3, an antigen-based vaccine, showed promising results in melanoma-associated antigen A3 positive lung cancer patients who underwent resection in the phase II study; however, no improvement in progression-free survival was observed in the phase III MAGRIT study. CIMAVax is a recombinant human epidermal growth factor (EGF) vaccine that induces anti-EGF antibody production and prevents EGF from binding to its receptor. It has improved overall survival in patients with advanced NSCLC who achieve seroconversion. Ipilimumab, an immune checkpoint inhibitor that targets cytotoxic T-lymphocyte antigen 4, demonstrated improved progression-free survival in advanced NSCLC patients who received the drug after chemotherapy in a phased regimen. Finally, anti-programmed death receptor 1 agents have achieved durable response rates in phase I studies. This review gives an overview of the current data and the most promissory immunotherapeutic agents for NSCLC.

3PD Liquid biopsy in patients with adenocarcinoma of the lung and its correlation with their tumor tissue molecular profile

Background: Adequate quantity of tumor tissue for molecular analysis is a major handicap to deliver personalized medicine. Reasons such as difficulty to perform tumor biopsy (TBX) either because of tumor location, patient’s co-morbid conditions or the fact we need to repeat the TBX are among the common factors for lack of molecular profiling results (MPR). Hence, liquid biopsy (LBX) has emerged as a potential alternative to detect these genomic alterations. Methods: We analyzed 59 patients with stage IV or recurrent adenocarcinoma of the lung (ADENO) using Guardant 360 test; sample collections were done at Lynn Cancer Institute and Memorial Cancer Institute. Alterations detected by this test include single nucleotide variations, amplifications, ALK, FGFR2, FGFR3, RET, ROS1, NTRK1 genes, and short insertions/duplications/deletions in exons 19 and 20 of the EGFR and ERBB2 genes as well as exon 14 skipping of the MET gene. We compared these results with their tumor tissue MPR in each individual, to assess their correlation. Results: 41/59 pts were females; median age 75 (range, 27–99). 44 pts (75%) had at least 1 genomic alteration by LBX (range, 1–10). Most common abnormalities found in LBX: EGFR (20 pts), TP53 (19 pts), and NF1 (11 pts). From this 44 pts with + LBX results, 29 pts (66%) had tumor tissue MPRs for comparison. Major reason for lack of tumor tissue MPRs: insufficient tumor (11/17; 65%). For comparison between the 2 modalities, we considered all pts with available results in both tests (n = 42 pts); 20 pts (48%) had at least 1 genomic abnormality or no abnormality identify in both type of “biopsies”. Most of the concordance was in EGFR mutations; LBX caught 12/17 (71%) EGFR mutations in TBX. Nonetheless, LBX caught 11 EGFR alterations not present or available by TBX MPR. Conclusions: Insufficient amount of tumor is the reason for lacking tumor MPRs. LBX offers an alternative/complementary way to identify genomic alterations in a much easy way. Our cohort had 48% concordance between LBX and TBX; however, for EGFR mutation, correlation was higher (71%). Discrepancies between both modalities could be explained by timing when samples were taken and tumor heterogeneity. Updated data with 90 pts will be presented at the meeting. Legal entity responsible for the study: Lynn Cancer Institute Research Department Funding: Lynn Cancer Institute Research Department Disclosure: L. Raez, B. Hunis: Research support: Liquid Genomics; Exosomes. All other authors have declared no conflicts of interest. 4P Co-amplifications of PD-L1/PD-L2 genes (9p24.1) and PD-L1 protein expression in NSCLC patients

PS4 Clinical Outcomes in Hispanic Patients Treated with Checkpoint Inhibitors

nivolumab + ipilimumab and chemotherapy, respectively. Grade 3e4 select TRAEs by category with nivolumab + ipilimumab included hepatic (8%), endocrine (4%), and skin (4%), and were consistent with previous reports. Median time to onset of select TRAEs ranged from 2 to 15 weeks, and the majority resolved (median time: 10 weeks). PRO results will be reported in the final presentation. Conclusion: First-line nivolumab + ipilimumab significantly prolonged PFS vs chemotherapy in patients with NSCLC and high TMB 10 mut/Mb regardless of PD-L1 expression. These results validate the role of TMB as a biomarker for the use of nivolumab + ipilimumab in first-line NSCLC. Safety of nivolumab + low-dose ipilimumab was manageable.

PS5 New Biomarkers to Follow Therapy Response in Plasma of NSCLC Patients

nivolumab + ipilimumab and chemotherapy, respectively. Grade 3e4 select TRAEs by category with nivolumab + ipilimumab included hepatic (8%), endocrine (4%), and skin (4%), and were consistent with previous reports. Median time to onset of select TRAEs ranged from 2 to 15 weeks, and the majority resolved (median time: 10 weeks). PRO results will be reported in the final presentation. Conclusion: First-line nivolumab + ipilimumab significantly prolonged PFS vs chemotherapy in patients with NSCLC and high TMB 10 mut/Mb regardless of PD-L1 expression. These results validate the role of TMB as a biomarker for the use of nivolumab + ipilimumab in first-line NSCLC. Safety of nivolumab + low-dose ipilimumab was manageable.

P2.01-056 Use of Cell-Free Circulating RNA (cfRNA) Expression of PD-L1 and ERCC1 in Plasma to Monitor Response to Therapy in NSCLC

Quantitative levels of ERCC1 cfRNA are used to monitor/predict a clinical response with respect to a disease state of a cancer in a patient subject to treatment with a platinum-based drug. Most typically, the cancer is a NSCLC and the patient is treated with a platinum-based drug. Where treatment also includes immune checkpoint inhibitors, PD-L1 cfRNA may be quantified to further predict treatment outcome.

P1.29: “Real World” Use of Liquid Biopsy in Patients With Lung Adenocarcinoma and Correlation With Tumor Tissue Genetic Profile: Track: Advanced NSCLC

blood vessel invasion detected in 32 patients. Distal recurrence sites after curative resection were lung (10/22patients:45.5%), bone (6:27%), mediastinal lymph nodes(6), brain(6), paraadrenal(5:23%) chest wall or pleura(4:18%) and femoral muscle(1:5%). Fiveyear overall survival and disease-free survival were 43.5% (N0:71%, N1+N2 35%), disease-free survival was 50.2%. Adjuvant chemotherapy was performed in 21patients. Among the 21 patients who received adjuvant chemotherapy, four cycles of carboplatin with pemetrexed, paclitaxel or gemcitabine chemotherapy were performed in 20 (95%) patients. Among the 21 patients who underwent adjuvant chemotherapy, there was no mortality related to chemotherapy. Conclusion: It was difficult to have preoperative exact diagnosis with pleomorphic carcinoma.Many long survival patients had N0-histological component of sarcoma or adenocarcinoma tumor with platinumdoublet adjuvant chemotherapy. It is necessary to select appropriate treatment strategies to prevent postoperative recurrence even for early staged patients.

PD2.01 (also presented as P1.13): Lung Cancer Chromosomal Aberrations and Gene Expression Profiles of Hispanics Living in the US or Latin America are Similar

POSTER DISCUSSION SESSION 2 SATURDAY, AUGUST 27, 2016 e 08:00 e 09:15 PD2.01 (also presented as P1.13) Genes Evaluated by GEP # Tumors Tested Frequency % Hispanics % NHW % EGFR 380 22% 25% 21% ALK 339 5% 5% 5% Lung Cancer Chromosomal Aberrations and Gene Expression Profiles of Hispanics Living in the US or Latin America are Similar ROS-1 180 8% 3% 9% KRAS 258 30% 27% 31% c-MET 165 31% 27% 32%

Making steps to decrease emergency room visits in patients with cancer: Our experience after participating in the ASCO Quality Training Program.

51 Background: Overutilization of emergency room services by oncology patients is a known problem associated with increased admission rates and health care expenditure. A review of our oncology patients emergency room (ER) visits from January to May 2015 demonstrated that 48% of ER visits happened during office hours. Consequently a rapid cycle quality improvement project was developed with an aim to decrease ER visits by 30% by September 2015.nnnMETHODSnA multidisciplinary team completed an action plan, starting with a project charter and definition of aim statement. A process map for patient scheduling/triage was created. A cause and effect diagram helped identify potential causes patient utilization of the ER. Diagnostic data were obtained querying our EMR (EPIC) for ER visits from January to May 2015. A Pareto chart identified Breast, Hematology and GI malignancies as main diagnosis utilizing the ER. Plan-do-study-act (PDSA) #1 began with development of a protocol to guide the handling of patients calls that could previously resulted in an ER visit. Staff from the patient access center (PAC), a telephone operator service, and physicians offices were trained on its application. PDSA #2 focused on patient education to the importance of contacting the PAC for any concern or symptom related to active chemotherapy treatment.nnnRESULTSnThe implementation of a triage system at our PAC resulted in a 60% decrease in the number of patients utilizing the ER, which met our goal. Patients calls to the PAC have increased. Two new materials were developed: a telephone triage form categorizing the patients complaint and the resulting action by our PAC center staff, and a patient Clinical Intervention Triage Tracking Log which allowed for the tracking of all patients triaged, their data, and the responsible team member.nnnCONCLUSIONSnThis study suggests that the development of a tool to properly identify and address emergent chemotherapy symptoms without utilizing the ER during working hours resulted in an intervention that positively affected the pre-specified endpoint.