Abstract: e21579 Background: P and P+C are standard-of-care (SOC) treatment options for advanced NSCLC. However, they have not yet been directly compared in clinical trials. Methods: We conducted a retrospective cohort study of patients with advanced NSCLC who initiated treatment with SOC P±C at our center from 2/11/16 to 10/15/19 (data cutoff 1/15/20). Patient demographic, clinicopathologic, therapeutic and outcomes data were extracted. All radiographic scans were independently evaluated by a thoracic radiologist using iRECIST. Survival time was defined from the start of P±C. Kaplan-Meier and Cox proportional hazards model were utilized. Results: Of 103 patients with median follow up of 17.7 months, 74 (71.8%) had received P, while 29 (28.2%) had received P+C. In PD-L1 tumor proportion score (TPS) unselected population, there were no significant differences in age, sex, smoking status, driver mutation, tumor mutational burden (TMB), line of therapy, ECOG performance status (PS) or immune-related adverse events (irAE) between P and P+C groups. 71.6% in P vs 13.8% in P+C had PD-L1 TPS ≥50% (p 〈 0.001). There were no significant differences between the two groups in objective response rate (ORR), disease control rate (DCR), unadjusted progression-free survival (PFS) or unadjusted overall survival (OS) (Table). Multivariable adjustment for confounding factors between P+C vs P revealed no differences in OS [hazard ratio (HR) for death, 1.53, 95% CI 0.55 – 4.25] or PFS [HR for progression/death, 1.75, 95% CI 0.63 – 4.91] . Further stratification into PD-L1 TPS ≥50% and 〈 50% showed no significant differences between P+C vs. P in adjusted OS [HR for death, TPS 〈 50%- 1.54 (95% CI 0.59 – 4.03); TPS ≥50%- 0.71 (95% CI 0.11 – 4.52)] or PFS [HR for progression/death, TPS 〈 50%- 1.58 (95% CI 0.72 – 3.48); TPS ≥50%- 0.64 (95% CI 0.06 – 6.93)]. ECOG PS and development of irAE influenced OS in all groups, while TMB was relevant in PD-L1 ≥50% only. Conclusions: Our study shows no significant differences in outcomes with P vs P+C in advanced NSCLC in a real-world setting, albeit with limitations of single-center design, limited sample size, different line settings and lack of disease burden stratification. Ongoing phase III trials comparing front line P vs P+C will definitively address the long-term clinical benefits -if any- of combining cytotoxic chemotherapy with anti-PD-1 drugs. [Table: see text]

Abstract: 9533 Background: Pembrolizumab (P) is now widely used as standard of care (SOC) in advanced NSCLC. We sought to identify prognostic factors influencing survival with it in a real-world setting. Methods: We conducted a retrospective cohort study of with advanced NSCLC patients who initiated treatment with SOC P monotherapy at our center from 2/11/16 to 10/15/19 (data cutoff 1/15/20). Patient demographic, clinicopathologic, therapeutic and outcomes data were extracted. Survival time was defined from start of P. Cox proportional hazards and logistic regression were utilized. Results: Of 74 patients with median follow up of 83.9 weeks, 30 (40.5%) were alive at cutoff. Patient characteristics at start of therapy were: 36 (48.6%) female, median age 68.5 yr (range 33-87), 10 (13.5%) with symptomatic brain metastases; 54 (72.9%) treatment-naïve, 29 (39.2%) with ECOG performance status (PS) ≥2. Tumor characteristics were: 53 (71.6%) with PD-L1 tumor proportion score (TPS) ≥50%, median PD-L1 TPS 75% (range 1-100), tumor mutational burden (TMB) tested in only 37 (50%) patients, median TMB 8 mut/mB (range 1-62). Any grade immune-related adverse events (irAE) occurred in 33 (44.6%) patients, while 16 (21.6%) received systemic steroids. Median survival was 43.3 wks (95% CI 29-104.1). Multivariable regression showed ECOG PS of ≥2 as the strongest risk factor for death (Table). We next evaluated differences in characteristics of patients who were alive vs dead within 12 wks of starting P, by which initial response assessments are completed in routine practice. ECOG PS was the only significantly different baseline variable, even after multivariable adjustment (p = 0.002). Conclusions: ECOG PS of ≥2 is a poor prognostic risk factor associated with P monotherapy in advanced NSCLC. Though comprising a clinically significant subset of patients in real-world, they were not included in landmark trials (KEYNOTE-024 & 042). Prospective evaluation is warranted. [Table: see text]

Abstract: 11028 Background: Evidence shows that cancer patients are interested in learning about medicinal cannabis and frequently ask their oncologists for recommendations. To determine whether oncology training is adequately preparing physicians to address this topic, we conducted a national survey of oncology trainees to determine attitudes, practices, and knowledge about medical cannabis in cancer care. Methods: An interdisciplinary team developed an electronic questionnaire assessing trainees’ current practices regarding cannabis recommendations in cancer care and their knowledge of its effectiveness and risks compared with conventional care for cancer-related symptoms. We contacted 155 oncology training programs throughout the U.S. and asked that they distribute the survey to their trainees. Primary outcomes were: whether trainees reported discussing or recommending cannabis with/to patients and whether they felt sufficiently informed to make such recommendations. We presented data as proportions and used chi-square tests to compare proportions between groups. Results: Forty training programs from 25 states participated; of the 462 trainees in these programs, 187 completed surveys, yielding a response rate of 40%. Of the participants, 52% were female, 53% White, 33% Asian, and 5% Hispanic. One third (34%) graduated medical school before 2015, and 22% attended medical school outside the US. While 24% of trainees reported having received training regarding medical cannabis, only 12% felt sufficiently informed to make cannabis recommendations. Despite this, 91% reported having discussed cannabis with patients, and 58% reported recommending cannabis clinically to more than five patients in the prior year. Many viewed it as useful adjunctive therapy that was at least as effective as conventional treatments for: anorexia/cachexia (72%), nausea/vomiting (45%), and pain (41%). Over half (55%) believed that cannabis was beneficial to patients at the end of life; 31%, patients in active treatment; 11%, cancer survivors; 20%, the elderly with cancer and 16%, young adults with cancer. Peer-reviewed material (30%), lectures or webinars by another physician (29%), and patients and their families (22%) were the most commonly cited sources of information regarding medical cannabis. Oncologists who reported at least one area of focus as supportive/palliative care were more likely to feel sufficiently informed to make recommendations than oncologists without this focus (17% vs. 4%, P = 0.01); no other demographic or practice characteristics were associated with feeling sufficiently informed (all P 〉 0.10). Conclusions: Although most oncology trainees discuss cannabis use with their patients, the majority do not feel sufficiently informed about its use in cancer care. This represents an unmet need in contemporary oncology training, trainee satisfaction, and patient care.

Abstract: 11013 Background: There is continued uptake in the use of medical cannabis (MC) among patients with cancer. Our group previously conducted a national study that showed that while a majority of oncology fellows discussed MC with patients, very few feel well informed in doing so. We hypothesized that an evidence-based curriculum on the use of MC for oncology trainees is feasible to develop and would be effective in improving confidence to discuss MC with patients. Methods: A multidisciplinary expert team designed an evidence-based educational curriculum in 5 modules specifically for MC in oncology populations that included pharmacology/history, symptom management, cancer-directed effects, toxicities and practical/logistic concerns. The curriculum was piloted as a one-hour webinar at three US hematology oncology fellowship training programs in 2022-2023. Anonymous incentivized survey instruments that were designed to assess self-perceived knowledge, attitudes and behaviors pertaining to MC (on a 5-point Likert scale; strongly agree to strongly disagree) were distributed anonymously via email at the pilot (t = 0) and immediately after (t + 7 days); additional delayed surveys (t+90 days) are in progress. Results: Of 35 eligible trainees, 31 completed the pre-training surveys (88.6%), and 26 (74.3%) completed the post-training surveys. Most trainees indicated that the curriculum is helpful (88.5%, 95% CI: 69.8-97.6) and that they would recommend it to their colleagues (80.8%, 95% CI: 60.6-93.4). Following the webinar, there was significant improvement in self-reported comfort with discussing MC for symptom management (3.2% vs. 92.3%, P 〈 0.001), risks of MC (9.7% vs. 76.9%, P 〈 0.001) and modes of MC use (16.1 vs. 80.8%, P 〈 0.001). The majority of participants (80.0%, 95% CI: 59.3-93.2) reported that they were more likely to initiate conversations about MC with their patients after attending the webinar. Conclusions: In this multi-center study, we demonstrate that it is feasible to develop and deliver a fellow-focused, evidence-based curriculum for MC use in patients with cancer. The webinar was well received and demonstrated significant improvement in fellow-reported attitudes surrounding MC efficacy, risks, and modes of use. Further work to assess durability of the curriculum on knowledge, attitudes, and behaviors is ongoing.

Abstract: Background: Chronic graft versus host disease (cGVHD) remains a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HCT), with a cumulative incidence of 50% (Arora et al, Biol Blood Marrow Transplant 2016). Systemic corticosteroids are considered first-line therapy, and best approach to managing steroid-refractory cGVHD is lacking. Abatacept is a recombinant fusion protein consisting of the extracellular domain of human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc portion of human immunoglobulin G1 (IgG1) to prevent complement fixation and antibody-dependent cellular cytotoxicity. Abatacept is a selective costimulation modulator that binds specifically to CD80 and CD86 on antigen presenting cells, thus attenuating CD28-mediated T cell activation. We previously reported results from a Phase I clinical trial evaluating the safety and clinical efficacy of abatacept in patients with steroid-refractory cGVHD (Nahas et al, Blood 2018 #NCT01954979). Here we report results of the phase II study evaluating the overall clinical response rate of abatacept in patients with steroid-refractory cGVHD. Methods: Allogeneic bone marrow or stem cell transplantation recipients were eligible if they developed cGVHD as defined by NIH consensus criteria and were treated with prednisone ≥ 0.25 mg/kg/day for at least 4 weeks without complete resolution of signs and symptoms. Peripheral blood was drawn prior to each dose of abatacept and following completion of therapy to assess the effect of treatment on circulating T cells. Abatacept was administered at 10mg/kg for a total of 6 doses. Doses 1-3 were administered at two-week intervals. One month after administration of Dose 3, abatacept was given at four-week intervals for Doses 4-6. Patients who completed 6 doses of abatacept and continued to demonstrate response were eligible to receive extended duration therapy with monthly abatacept at a dose of 10mg/kg for up to a total of 12 additional doses. Primary study endpoint was overall response rate (ORR) of using abatacept in treating cGVHD. Complete response (CR) was defined as resolution of all manifestations in each organ or site, and partial response (PR) was defined as improvement in at least one organ or site without progression in any other organ or site as per the 2014 NIH Chronic GVHD Consensus Response Criteria (Lee et al Biol Blood Marrow Transplant 2015). Results: 39 subjects with median age of 62 years (range 25-77 years) had undergone HCT a median of 43 months (range 6-173 months) prior to study entry. Patients were treated with abatacept and received a median of 8 doses (range 2-18). 17 patients had moderate cGVHD and 22 patients had severe cGVHD at baseline. Baseline cGVHD assessment of the 39 evaluable patients showed involvement of the skin in 85% (n=33), mouth in 44% (n=17), eyes in 69% (n=27), gastrointestinal tract (GI) in 18% (n=7), liver in 23% (n=9), lung in 54% (n=21), joints in 82% (n=32), and genital tract in 8% (n=3). The ORR was 49% (19/39 patients) with CR 0% and PR 49%. The organ sites with greatest improvement included lung (33%), eyes (23%), mouth (21%), and joints (21%). Progression of disease occurred in 26% of patients (n=10), with sites of involvement including skin (8%), mouth (10%), eyes (5%), lung (3%), and joints (5%). Baseline median daily dose of prednisone was 20mg with a 27.5% reduction at 1-month follow-up to 14.5mg (p & lt;0.01) and 50% reduction at 5-month follow-up to 10mg (p=0.02). The most common adverse events were neutropenia, fatigue, headache, and upper respiratory infection (URI). No infusional reactions were observed. Nine events of neutropenia (5 Grade 2 , 2 Grade 3, 2 Grade 4) were reported in four patients. Infections were uncommon and included 1 Grade 2 eye infection, 2 Grade 2 lung infections, 1 Grade 3 lung infection, and 1 Grade 3 urinary tract infection. One patient died within 30 days from receiving the 6 th dose of abatacept due to concurrent HSV hepatitis. Conclusions: Abatacept is associated with a 49% ORR in steroid refractory cGVHD and leads to durable reduction in prednisone dosing over time. Severe infections are uncommon and the infusions are well tolerated. Abatacept represents a promising novel therapeutic agent for patients with steroid-refractory cGVHD. Disclosures Stroopinsky: The Blackstone Group: Consultancy. Arnason: Juno/BMS: Honoraria. Cutler: Cimeio: Consultancy; Editas: Consultancy; Kadmon: Consultancy; Pfizer: Consultancy; Mallinckrodt: Consultancy; CareDx: Consultancy; Incyte: Consultancy; Omeros: Consultancy; Syndax: Consultancy; Mesoblast: Consultancy; Deciphera: Consultancy; Jazz: Consultancy. Nikiforow: Kite/Gilead: Other: ad HOC Advisory Boards; Novartis: Other: ad Hoc Advisory Boards; Iovance: Other: ad Hoc Advisory Boards; Glaxo Smith Kline (GSK): Other: ad Hoc Advisory Boards. Avigan: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Kite Pharma: Consultancy, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Partner Tx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Aviv MedTech Ltd: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Parexcel: Consultancy; Takeda: Consultancy; Sanofi: Consultancy. Soiffer: Rheos Therapeutics, USA: Consultancy; Kiadis, Netherlands: Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics, USA: Other: Data Safety Monitoring Board; Precision Biosciences, USA: Consultancy; Jazz Pharmaceuticals, USA: Consultancy; Takeda: Consultancy; Jasper: Consultancy; Gilead, USA: Other: Career Development Award Committee; NMPD - Be the Match, USA: Membership on an entity's Board of Directors or advisory committees. Rosenblatt: Attivare Therapeutics: Consultancy; Parexel: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Imaging Endpoints: Consultancy; Wolters Kluwer Health: Consultancy, Patents & Royalties; Bristol-Myers Squibb: Research Funding.

Abstract: Non-small cell lung adenocarcinoma is the most common type of lung cancer but is often difficult to treat. New treatment options have emerged with the class of tyrosine kinase inhibitors, but it has been found that certain genetic mutations in the epidermal growth factor receptor (EGFR) receptor are not as sensitive to this treatment as others. We present a case of a 78-year-old man who was diagnosed with stage IV non-small cell lung adenocarcinoma with an EGFR exon 20 mutations treated with pemetrexed, nivolumab, and then docetaxel. He has lived over four years after his initial diagnosis. This case illustrates the importance of genetic testing of patients to evaluate for specific gene mutations. It highlights the fact that these patients with exon 20 mutations are not sensitive to tyrosine kinase inhibitor treatment and often respond better to chemotherapeutic agents.