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PURPOSE Oral chemotherapy challenges providers' abilities to safely monitor patients' symptoms, adherence, and financial toxicity. COVID-19 has increased the urgency of caring for patients remotely. Collection of electronic patient-reported outcomes (ePROs) has demonstrated efficacy for patients on intravenous chemotherapy, but limited data support their use in oral chemotherapy. We undertook a pilot project to assess the feasibility of implementing an ePRO system for patients starting oral chemotherapy at our cancer center, which includes both an academic site and a community site. METHODS Patients initiating oral chemotherapy were asked to participate. A five-question tool was built in REDCap. Concerning responses triggered outreach within one business day. The primary outcome was time to first symptom assessment. For comparison, we used a historical cohort of patients who had been prescribed oral chemotherapies by providers in the same disease groups at the cancer center. RESULTS Twenty-five of 62 (40%) patients completed ePRO assessments. Fifty historical charts were reviewed. Time to first symptom assessment was 7 days (IQR, 4-14 days) in the historical group compared with 3 days (IQR, 2-4 days) in the ePRO group. Time to clinical action was 14 days (7-35 days) in the historical group compared with 8 days (4-19 days) in the ePRO group. No statistically significant differences were detected in 30-day emergency department visit or hospitalization (12% for both groups) or 90-day emergency department visit or hospitalization rates (historical 28% and ePRO 20%). CONCLUSION An ePRO tool monitoring patient concerns about adherence, cost, and toxicities for patients with new oral chemotherapy regimens is feasible and improves time to symptom assessment. Further investigation is needed to improve patient engagement with ePROs and evaluate the long-term impacts for patients on oral chemotherapy.

PURPOSE Estrogen receptor (ER)–positive endometrial cancers (ECs) are characterized by phosphatidylinositol 3-kinase (PI3K) and receptor tyrosine kinase (RTK)/RAS/β-catenin (CTNNB1) pathway alterations in approximately 90% and 80% of cases, respectively. Extensive cross-talk between ER, PI3K, and RTK/RAS/CTNNB1 pathways leads to both ligand-dependent and ligand-independent ER transcriptional activity as well as upregulation of cyclin D1 which, in complex with cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), is a critical regulator of cell cycle progression and a key mediator of resistance to hormonal therapy. We hypothesized that the combination of the aromatase inhibitor letrozole and CDK4/6 inhibitor abemaciclib would demonstrate promising activity in this setting. METHODS We conducted a phase II, two-stage study of letrozole/abemaciclib in recurrent ER-positive EC. Eligibility criteria included measurable disease, no limit on prior therapies, and all EC histologies; prior hormonal therapy was allowed. Primary end points were objective response rate by RECIST 1.1 and progression-free survival (PFS) rate at 6 months. RESULTS At the data cutoff date (December 03, 2021), 30 patients (28 with endometrioid EC) initiated protocol therapy; 15 (50%) patients had prior hormonal therapy. There were nine total responses (eight confirmed), for an objective response rate of 30% (95% CI, 14.7 to 49.4), all in endometrioid adenocarcinomas. Median PFS was 9.1 months, PFS at 6 months was 55.6% (95% CI, 35.1 to 72), and median duration of response was 7.4 months. Most common ≥ grade 3 treatment-related adverse events were neutropenia (20%) and anemia (17%). Responses were observed regardless of grade, prior hormonal therapy, mismatch repair, and progesterone receptor status. Exploratory tumor profiling revealed several mechanistically relevant candidate predictors of response ( CTNNB1, KRAS, and CDKN2A mutations) or absence of response ( TP53 mutations), which require independent validation. CONCLUSION Letrozole/abemaciclib demonstrated encouraging and durable evidence of activity in recurrent ER positive endometrioid EC.

On May 5, 2021, the Colorado Department of Public Health and Environment (CDPHE) identified the first five COVID-19 cases caused by the SARS-CoV-2 B.1.617.2 (Delta) variant in Mesa County in western Colorado (population 154,933

Public two-year colleges offer an entry point to postsecondary education for many Americans who might otherwise forgo college. Most students leave college without a credential. A growing body of research examines the returns to higher education among two-year college entrants but primarily focuses on returns to credentials. This study examines the returns to different types of credits, including academic, technical, and developmental credits. In a series of individual fixed effects models, we use state administrative data following a population of public two-year college entrants to understand which college credits yield the greatest returns and how returns to credits vary across degree attainment. Our findings illustrate that average estimates of the returns to credits obscure varied patterns of returns among two-year college students, where sub-baccalaureate credential recipients appear to experience different returns to academic and technical credits compared with their peers.

ImportanceAlthough the activity of pembrolizumab and lenvatinib (the only US Food and Drug Administration–approved immunotherapy for mismatch repair proficient endometrial cancer [MMRP EC]) is compelling, there are no biomarkers of response and most patients do not tolerate, do not respond to, or develop resistance to this regimen, highlighting the need for additional, potentially biomarker-driven therapeutic approaches for patients with recurrent MMRP EC.ObjectiveTo assess the potential positive outcomes and safety of the combination of the polyadenosine diphosphate-ribose polymerase inhibitor talazoparib and the programmed cell death ligand 1 (PD-L1) inhibitor avelumab in recurrent MMRP EC.Design, Settings, and ParticipantsThis investigator-initiated, open-label, single-arm, 2-stage, phase 2 study nonrandomized controlled trial patients at 4 institutions in the US. Key eligibility criteria included measurable disease, unlimited prior therapies, and all endometrial cancer histologies.InterventionsTalazoparib, 1 mg, orally, daily, and avelumab, 10 mg/kg, intravenously, every 2 weeks, were administered until disease progression or unacceptable toxic effects.Main Outcomes and MeasuresStatistical considerations were developed for 2 coprimary objectives of objective response rate and rate of progression-free survival at 6 months, with a 2-stage design that allowed for early discontinuation for futility. Prespecified exploratory objectives included the association of immunogenomic features (determined by targeted-panel next-generation sequencing and immunohistochemistry) with activity.ResultsThirty-five female patients (mean [SD] age, 67.9 [8.41] years) received protocol therapy; 9 (25.7%) derived clinical benefit after meeting at least 1 of the 2 coprimary end points. Four patients (11.4%) exhibited confirmed objective response rates (4 partial responses), and 8 (22.9%) survived progression free at 6 months. The most common grade 3 and 4 treatment-related toxic effects were anemia (16 [46%]), thrombocytopenia (10 [29%]), and neutropenia (4 [11%]); no patient discontinued receipt of therapy because of toxic effects. Tumors with homologous recombination repair alterations were associated with clinical benefit from treatment with avelumab and talazoparib. Tumor mutational burden, tumor-infiltrating lymphocytes, and PD-L1 status were not associated with clinical benefit.Conclusions and RelevanceThe results of this nonrandomized controlled trial suggest that treatment with avelumab and talazoparib demonstrated a favorable toxic effect profile and met the predetermined criteria to be considered worthy of further evaluation in MMRP EC. Immunogenomic profiling provided insights that may inform ongoing and future studies of polyadenosine diphosphate-ribose polymerase and PD-L1 inhibitor combinations in endometrial cancer.Trial RegistrationClinicalTrials.gov Identifier: NCT02912572

Introduction The advent of immunotherapy has revolutionized cancer therapy in recent years. Immunotherapy using monoclonal antibodies against checkpoint molecules, including programmed death (PD)-1, PD ligand (PD-L)1, and cytotoxic T-lymphocyte antigen 4 (CTLA)-4, has become a cornerstone in cancer therapy. However, due to the physiologic role of checkpoint molecules in preventing autoimmunity, immune-related adverse events (irAEs) have emerged as frequent complications. As the use of immunotherapy increases, a better understanding of irAEs and screening tools for timely diagnosis and management are needed. Materials and methods We surveyed oncology providers at our institution with 10 questions assessing their knowledge, and comfort levels in diagnosing and managing endocrine irAEs. We created an endocrine clinic referral order specifically for oncology-related endocrinopathies and created a screening tool for diagnosing these endocrinopathies. We met with our oncology providers in three different hour-long sessions. A post-intervention survey was sent out six months after our initial meeting to assess changes in the participants' knowledge and comfort levels. We also reviewed the electronic medical records system for the number of new referrals to endocrinology clinic. Results A total of 27 (N) participants responded to the initial survey and 14 (n) responded to the subsequent survey six months later. Based on the initial survey, only a minority (26%) of respondents were comfortable diagnosing and managing (15%) immunotherapy-related adrenal dysfunction whereas more respondents were comfortable diagnosing (55%) and managing (56%) thyroid dysfunction. The majority (67%) of the respondents knew which immunotherapies commonly are implicated in hypophysitis but only 42% of them were aware of the next steps of its management. We noted a significant increase in self-reported comfort levels in diagnosing (p0.05) and managing (p0.05) adrenal disorders post-intervention. There was also a trend of improvement in participants' comfort levels regarding diagnosing and managing thyroid dysfunction, management of hypophysitis, and immunotherapies implicated in thyroid dysfunction but the changes did not reach statistical significance. There was no significant change in their knowledge regarding immunotherapies implicated in hypophysitis and natural history of thyroid dysfunction in this setting. In the six months following our intervention, 30% (n=21) of the patients referred to the endocrine clinic were for immune-related endocrinopathies compared to 19% (n=7) of patients over a similar duration before the intervention. Data on the time between referral and endocrinology appointment was available for 16 out of the 21 patients and the mean (±SD) time to endocrine clinic appointment was 2.66 (±1.95) weeks. Nine (43%) of the 21 referred patients were seen in endocrinology clinic within two weeks. Conclusions Although immune-related endocrinopathies are rarely fatal, they have a significant impact on patients' quality of life. Endocrinopathies are typically manageable with prompt recognition and treatment. But the subtle and non-specific manifestations make the diagnostic process a challenge. Standardized and practical screening tools can help in diagnosing these adverse events promptly, seeking specialized care if needed and may also aid in reducing healthcare-related costs.

ObjectiveThe Comprehensive Score for Financial Toxicity (COST) is a validated instrument measuring the economic burden experienced by patients with cancer. We evaluated the frequency of financial toxicity at different COST levels and stratified risk factors and associations with cost-coping strategies by financial toxicity severity.MethodsWe analyzed previously collected survey data of gynecologic oncology patients from two tertiary care institutions. Both surveys included the COST tool and questions assessing economic and behavioral cost-coping strategies. We adapted a proposed grading scale to define three groups: no/mild, moderate, and severe financial toxicity and used χ2, Fisher’s exact test, and Wilcoxon rank sum test to compare groups. We used Poisson regression to calculate crude and adjusted risk ratios for cost-coping strategies, comparing patients with moderate or severe to no/mild financial toxicity.ResultsAmong 308 patients, 14.9% had severe, 32.1% had moderate, and 52.9% had no/mild financial toxicity. Younger age, non-white race, lower education, unemployment, lower income, use of systemic therapy, and shorter time since diagnosis were associated with worse financial toxicity (all pConclusionsAmong a geographically diverse cohort of gynecologic oncology patients, nearly half reported financial toxicity (COST

Objective Genomic alterations of BCOR via ZC3H7B-BCOR fusion or BCOR internal tandem duplication (ITD) define a subset of endometrial stromal sarcoma (ESS). The goals of this study were to: 1) determine the molecular landscape of BCOR-rearranged ESS, 2) to identify novel BCOR fusion gene partners in ESS and their associated clinicopathological characteristics, and 3) to potentially unravel targetable genomic alterations in BCOR-mutated ESS. Methods A retrospective database search of a CLIA-certified molecular laboratory was performed for uterine sarcomas that contained BCOR rearrangements or BCOR ITD. The cases were previously assayed by comprehensive genomic profiling via both DNA- and RNA-based targeted next generation sequencing during the course of clinical care. Clinicopathological and genomic data was centrally re-reviewed. Results We identify largest cohort of BCOR-rearranged ESS to date (n = 40), which included 31 cases with canonical ZC3H7B-BCOR fusion as well as 8 cases with novel BCOR gene rearrangement partners, such as BCOR-L3MBTL2, EP300-BCOR, BCOR-NUTM2G, BCOR-RALGPS1, BCOR-MAP7D2, RGAG1-BCOR, ING3-BCOR, BCOR-NUGGC, KMT2D-BCOR, CREBBP-BCOR and 1 case with BCOR internal rearrangement. Re-review of cases with novel rearrangements demonstrated sarcomas with spindle, epithelioid or small round cell components and frequent myxoid stromal change. Comprehensive genomic profiling revealed high frequency of CDK4 and MDM2 amplification in 38% and 45% of BCOR-rearranged cases, respectively, and homozygous deletion of CDKN2A, which encodes an inhibitor of CDK4 in 28% of cases. Notably, CDK4 and MDM2 amplification was absent in all cases from 15 different ESS cases harboring BCOR ITD. Conclusions Alterations of CDK4 pathway members, for which targeted therapy is clinically available (i.e. palbociclib), via CDK4 amplification or CDKN2A loss, contributes to the pathogenesis of BCOR-rearranged uterine sarcomas, which may have therapeutic implications.

Objective Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) and SMARCA4-deficient undifferentiated uterine sarcoma (SMARCA4-DUS) are rare and aggressive tumors, primarily affecting pre- and perimenopausal women. Inactivating SMARCA4 mutations are thought to be the driving molecular events in the majority of these tumors. Here, we report the clinical course of a family with germline SMARCA4 mutation and compare large cohorts of these rare tumor types. Methods We extracted clinico-pathological medical record data for the family with germline SMARCA4 mutation. Clinico-genomic data from SCCOHT and SMARCA4-DUS cohorts were retrospectively extracted from the archives of a large CLIA-certified reference molecular laboratory. Results We identified a single family with an inherited germline SMARCA4 mutation, in which two different family members developed either SCCOHT or SMARCA4-DUS, both of whom died within one year of diagnosis, despite aggressive surgical, chemotherapy and immunotherapy treatment. Retrospective comparative analysis of large SCCOHT (n = 48) and SMARCA4-DUS (n = 17) cohorts revealed that SCCOHT patients were younger (median age: 28.5 vs. 49.0) and more likely to have germline SMARCA4 alterations (37.5% vs. 11.8%) than SMARCA4-DUS patients. Conclusions Growing understanding of the role SMARCA4 plays in the pathogenesis of these rare cancers may inform recommended genetic testing and counseling in families with these tumor types.

Supplemental material, sj-pdf-1-epx-10.1177_08959048211049415 for Getting to the Core of Credit Transfer: How Do Pre-Transfer Core Credits Predict Baccalaureate Attainment for Community College Transfer Students? by Lauren Schudde, Ibrahim Bicak and Shea Meghan in Educational Policy

319 Background: The medical oncology infusion unit at Beth Israel Deaconess Medical Center (BIDMC) experienced six anaphylactic reactions to chemotherapy between June 2000 and April 2021. EpiPen was delayed in all cases. In one instance, a patient experienced an emergency where she could not breathe, and her blood pressure continued to decrease. The covering nurse hesitated before administering an EpiPen. In follow-up, nurses reported a lack of confidence in administering an EpiPen. No licensed independent provider (LIP) was stationed in the infusion unit to guide nurses. The project's goal was to facilitate timely EpiPen administration, guided by the Translating Evidence into Practice (TRIP) framework. Methods: The project lead and the medical director revised the hospital’s chemotherapy reaction guidelines to highlight anaphylaxis management. They established an interdisciplinary project team with medical, nursing, pharmacy, and informatics representatives. Interventions, which started in November 2021, included a reaction management algorithm and PRN-reaction orders allowing nurses to initiate interventions while waiting for a LIP arrival. The unit educator provided EpiPen training, and the pharmacy leaders created an adverse drug reactions (ADR) kit—a locked box with necessary medications that followed BIDMC’s institutional algorithm to manage infusion reactions. Results: The project team collected post-intervention data between December 2021 and April 2022. Nurses reported twenty mild-to-severe chemotherapy reactions, including four anaphylactic episodes. Nineteen patients were discharged home on the day of reactions, and one patient required hospital admission for persistent symptoms. The management algorithm was followed in ten reactions (50%). Deviations from the algorithm were noted in eight cases, with the most frequent reason being smaller doses of antihistamine or corticosteroid. The algorithm was not applicable in two cases with atypical patient symptoms. In seventeen of the twenty reactions (85%), PRN-reaction orders were available in the electronic ordering system. The ADR kit was used in all reactions. In two of the four anaphylactic reactions, EpiPen was administered immediately following hypotension or hypoxia. In the remaining two cases, it was administered for persistent symptoms. Conclusions: The project facilitated EpiPen administration. The critical steps were systemic analysis of barriers, problem-solving with the TRIP framework, and engagement of frontline nurses. In our next step, we will consider narrowing the scope to managing acute hypotension or hypoxia. The narrower scope will enable targeted education about emergency management, potentially at the hospital’s simulation center. To ensure every patient has an order, the department could consider a standing EpiPen order for hemodynamically unstable patients.

42 Background: COVID-19 presents a particular challenge in oncology, as in-person visits and treatments can be delayed during infection and patients are at risk for prolonged viral shedding. Our center uses two consecutive negative PCR tests for patients to return to clinic. As vaccination rates increase, we questioned the need for this strategy vs a time-based clearance approach. Methods: We identified cancer patients who tested positive for COVID-19 from 10/1/2021 to 3/31/2022 at a single tertiary care center and performed chart review under an IRB-approved protocol. Subgroups were compared using the Welch’s t-test and Welch’s ANOVA for 2 or > 2 groups, respectively. Results: 169 patients were identified. 153 had documented clearance defined as two consecutive negative PCR tests. The mean clearance time was 35.7 days (95% CI 32.3-39.0). There was a trend toward longer clearance time in patients with hematologic vs solid tumors (39.6 vs 33.2, p =.06) and a significant increase in patients treated with B cell depletion (58.0) vs chemo/targeted therapy (35.7, p =.01) or immunotherapy (29.0, p =.004). No significant difference was found by vaccination status or between the Delta and Omicron waves. If defined as one negative test, mean clearance time was 25.9 days (95% CI 23.6-28.1), and there was a significant difference in patients with hematologic vs solid tumors and in those treated with B cell depletion vs other therapies. However, 16.0% (27/169) of patients had a subsequent positive test after a first negative result, with increased incidence in patients with hematologic malignancy (26.2%, 16/61) and stem cell/adoptive cell transplant (46.2%, 6/13). Conclusions: COVID-19 is a significant barrier to oncologic care, and clearance times remain longer than reported for the general population. In this single center study, clearance time was > 1 month and further increased in patients with hematologic malignancy or on B cell depleting therapy. While adjusting clearance criteria to a single negative test or specific timeframe may be an attractive option to reduce delays, a large proportion of patients may have further positive PCR testing.[Table: see text]

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A healthy 51-year-old woman presented with increasing abdominal and pelvic pain. Computed tomography imaging of the abdomen and pelvis showed an 11.6-cm pelvic mass, retroperitoneal lymphadenopathy, right hydronephrosis, and mesenteric tumor deposits ( Fig 1A ). A serum CA-125 was elevated at 1,149 U/mL. She underwent primary surgical cytoreduction including hysterectomy, bilateral salpingo-oophorectomy, appendectomy, resection of pelvic tumor, omentectomy, and low anterior resection with colorectal anastomosis. Intraoperatively, she was noted to have bilateral ovarian masses, pelvic and para-aortic lymphadenopathy, and a 4-cm omental tumor; in addition, both the uterus and rectosigmoid colon had adherent tumor deposits. All gross tumor was resected during the procedure. Final pathology confirmed high-grade serous carcinoma of ovarian origin ( Fig 1B ) that was determined to be stage IIIC as a result of upper abdominal involvement with greater than 2-cm tumor deposits, as well as retroperitoneal lymph node involvement. She underwent germline genetic testing, which did not identify a mutation in the BRCA1, BRCA2, BRIP1, RAD51C, or RAD51D genes. She presented for adjuvant chemotherapy after an optimal (R0) resection.

e21033 Background: Osimertinib is a third-generation mutation-specific covalent tyrosine kinase inhibitor of epidermal growth factor receptor ( EGFR) that is used for first-line therapy in EGFR-mutated non-small cell lung cancer (NSCLC) based on results of the FLAURA trial. We performed a retrospective analysis of baseline characteristics and clinical outcomes in real-world patients treated with osimertinib. Methods: We queried medical records at our NCI-designated cancer center hospital, Beth Israel Deaconess Medical Center (Boston, MA), for patients with unresectable EGFR-mutated NSCLC treated with first-line osimertinib. 56 patients were identified who initiated treatment with osimertinib from October 2017 to February 2021. Patient demographic information, treatment duration and next generation sequencing data were collected. Patients were determined to be FLAURA-eligible or FLAURA-ineligible based on published FLAURA trial inclusion and exclusion criteria. Time to discontinuation (TTD) of osimertinib was defined as months between osimertinib initiation and discontinuation. Median TTD and median OS were calculated. Results: Of the 56 patients included, 34 (61%) were female; 40 (71%) of patients were White, and 16 (29%) were Asian. 14 (25%) patients had an ECOG performance status of 2-4 at time of osimertinib initiation. Regarding EGFR mutation, 32 (57%) had exon 19 deletion and 16 (29%) had exon 21 L858R mutation. 8 (14%) patients had other EGFR mutations (not included in FLAURA) including: G719X, L861Q, and exon 20 insertion. In total, 25 (45%) patients were determined to be FLAURA-eligible, and 31 (55%) were FLAURA-ineligible. The most frequently occurring exclusionary comorbidities were concurrent active malignancy within two years (n = 9), baseline ECG abnormality (n = 9), and uncontrolled hypertension (n = 6). For clinical outcomes, the median TTD for all patients was 16.9 months (95% CI 12.6 – 35.1), whereas the median TTD was 31.1 months (95% CI 14.9 – NR) in the FLAURA-eligible cohort. Median OS for all patients was 32.0 months (95% CI 15.7 – NR) and not reached for the FLAURA-eligible cohort. No individual characteristic was associated with clinical outcomes using regression analysis. Conclusions: We report a single academic center’s experience with real-world osimertinib use in unresectable EGFR-mutated NSCLC – of which 55% of patients would have been ineligible for inclusion in the practice-changing FLAURA trial. Outcomes in the overall cohort (median TTD and OS) were comparable to the median PFS and OS, respectively, reported in the FLAURA study. Outcomes in our real-world FLAURA-eligible patients were better than previously reported. Our data supports the use of osimertinib in real-word settings and highlights the need for designing registration trials that are more inclusive of patient/disease characteristics seen in routine clinical practice.

We evaluated whether provision and promotion of improved sanitation hardware (toilets and child feces management tools) reduced rotavirus and human fecal contamination of drinking water, child hands, and soil among rural Bangladeshi compounds enrolled in a cluster-randomized trial. We also measured host-associated genetic markers of ruminant and avian feces. We found evidence of widespread ruminant and avian fecal contamination in the compound environment; non-human fecal marker occurrence scaled with animal ownership. Strategies for controlling non- human fecal waste should be considered when designing interventions to reduce exposure to fecal contamination in low-income settings. Detection of a human- associated fecal marker and rotavirus was rare and unchanged by provision and promotion of improved sanitation to intervention compounds. The sanitation intervention reduced ruminant fecal contamination in drinking water and general (non-host specific) fecal contamination in soil but overall had limited effects on reducing fecal contamination in the household environment.

Background Besides modeling/simulation-based analysis, no post-approval studies have evaluated optimal administration frequency of pembrolizumab in non-small cell lung cancer (NSCLC). Patients and Methods We performed a multicenter retrospective cohort study to evaluate association between survival outcomes and treatment extensions/delays of pembrolizumab-based regimens in advanced NSCLC patients. Those who had received at least four cycles in routine practice were divided into two groups: non-standard (Non-Std: ≥2 cycles at intervals >3weeks +3days) and standard (Std: all cycles every 3weeks or 1 cycle >3weeks +3days). Results Among 150 patients, 92 (61%) were eligible for the study (Non-Std:27, Std:65). Reasons for patients with extensions/delays in the Non-Std group included: immune-related adverse events (irAEs,33%), non-irAE-related medical issues (26%), and patient-physician preference (41%). Non-Std group was more likely to have higher PD-L1 tumor proportion score, higher number of treatment cycles and pembrolizumab monotherapy. Univariate and 6-month landmark analyses showed longer median overall survival (OS) and progression-free survival (PFS) in Non-Std group compared to the Std group. After multivariable adjustment for confounding factors, there was no significant difference in OS [HR 1.2 (95%C.I.: 0.3–4.8), p=0.824] or PFS [HR 2.6 (95%C.I.: 0.7–9.6), p=0.157] between the two groups. Conclusion Our study shows that a significant proportion of advanced NSCLC patients receive pembrolizumab-based regimens with extended intervals or delays in routine clinical practice and with similar outcomes to those receiving treatment at label-specified 3-week intervals. Given the durability of benefit seen and the potential for cost reduction and decreased infusion frequency in these patients, this requires validation in prospective trials., Highlights • The most cost-effective dosing frequency of pembrolizumab in advanced lung cancer is unknown. • We found delays/extensions of pembrolizumab-based treatment regimens in routine practice. • These delays/extensions were due to immune-related adverse events, medical issues or preferences. • Treatment delays/extensions were not associated with worse outcomes in advanced NSCLC. • Prospective trials are needed to evaluate extended pembrolizumab dosing regimens., The most cost-effective administration frequency of pembrolizumab in advanced non-small cell lung cancer (NSCLC) is unknown. We found that a significant proportion of these patients receive pembrolizumab-based regimens with extended intervals or delays in routine practice, with similar outcomes to those on label-specified 3-week interval treatments. Prospective evaluation of alternative dosing strategies is warranted to develop a more fiscally viable and patient-centered model.

Introduction Despite widespread administration of programmed death receptor 1 (PD-1) pathway inhibitors among individuals with NSCLC, little is known about the safety and activity of these agents among human immunodeficiency virus (HIV) – infected patients since this population has largely been excluded from immunotherapy clinical trials. Methods Here, we describe seven patients with metastatic NSCLC and HIV infection who were treated with PD-1 inhibitors nivolumab (two cases) or pembrolizumab (five cases with three in the first-line setting). Results Partial responses to immune checkpoint inhibitors were observed in three of seven cases. Among four patients with a programmed death ligand-1 tumor proportion score ≥50%, three partial responses were observed. All patients received antiretroviral therapy while on anti–PD-1 treatment. None of the patients experienced grade 3 or 4 immune-related adverse events or immune reconstitution inflammatory syndrome, and none required PD-1 inhibitor dose interruption or discontinuation due to toxicity. Conclusions Nivolumab and pembrolizumab can be safe and effective among patients with NSCLC and HIV. Larger studies will be needed to determine the overall safety and efficacy of immune checkpoint inhibitors among cancer patients with HIV.

Introduction Programmed death ligand 1 (PD-L1) testing of non–small cell lung cancer (NSCLC) specimens helps select patients most likely to respond to immune checkpoint inhibitors. PD-L1 immunohistochemical testing is approved for formalin-fixed, paraffin-embedded (FFPE) surgical pathology specimens; the testing performance on FFPE cytology cell block specimens is unknown, however. Materials and Methods The study is a retrospective cohort analysis of advanced-stage NSCLC patients treated at our institution where tumor PD-L1 expression using the clone 22C3 pharmDx kit (Agilent Technologies, Santa Clara, CA) on the Dako (Carpenteria, CA) Automated Link 48 platform was performed on either cytology cell block or surgical pathology specimens. Concomitant tumor mutation biomarkers were also collected, as well as tumor clinicopathologic characteristics and clinical outcome data following pembrolizumab treatment. Results A total of 232 patient tumor specimens were tested for PD-L1 expression (94 on cytology cell block and 138 on surgical pathology specimens). No significant differences in PD-L1 tumor proportion score (TPS) were observed between cytology and surgical pathology groups, with both patient cohorts containing ∼35% of tumors showing TPS ≥50%. Although few in number, patients with PD-L1 TPS ≥50% based on cytology versus surgical pathology who received treatment with pembrolizumab demonstrated similar response and disease control rates. Conclusions In this cohort of advanced NSCLC patients with standard of care PD-L1 testing performed on either FFPE cytology cell blocks or FFPE surgical pathology specimens, similar patterns were observed in population tumor PD-L1 expression patterns, concomitant driver mutations, and clinical response to palliative pembrolizumab in selected patients with TPS ≥50%.

OBJECTIVES: Financial toxicity is increasingly recognized as an adverse outcome of cancer treatment. Our objective was to measure financial toxicity among gynecologic oncology patients and its association with demographic and disease-related characteristics; self-reported overall health; and cost-coping strategies. METHODS: Follow-up patients at a gynecologic oncology practice completed a survey including the Comprehensive Score for Financial Toxicity (COST) tool and a self-reported overall health assessment, the EQ-VAS. We abstracted disease and treatment characteristics from medical records. We dichotomized COST scores into low and high financial toxicity and assessed the correlation (r) between COST scores and self-reported health. We calculated risk ratios (RR) and 95% confidence intervals (CI) for the associations of demographic and disease-related characteristics with high financial toxicity, as well as the associations between high financial toxicity and cost-coping strategies. RESULTS: Among 240 respondents, median COST score was 29. Greater financial toxicity was correlated with worse self-reported health (r = 0.47; p

TPS5609 Background: Despite significant strides in understanding the molecular pathogenesis of EC, there remain few effective therapies for recurrent disease. Deeper insight into the roles of disordered tumor vasculature and HIF1α- and VEGF-mediated immunosuppressive effects on myeloid-derived suppressor cells, T-cells, and PD-L1 expression contributed to the development of new targeted regimens. Activity of pembrolizumab and lenvatinib was demonstrated in a phase 2 trial in MMR-P EC (NCT02501096). By inhibiting VEGF receptor (VEGFR) and PD-L1 signaling, immunologically “cold” tumors may become inflamed. However, there are concerns regarding the toxicity of pembrolizumab/lenvatinib and alternatives are sought. The combination of the anti-PD-L1 antibody avelumab with axitinib, an inhibitor of VEGFR 1-3 and PDGFR with more potent IC50 inhibitory activity than lenvatinib, has also shown synergistic activity and is FDA approved as first line treatment for patients with renal cell cancer. We therefore hypothesized that this combination would be well tolerated and efficacious in recurrent MMR-P EC. Methods: This is an investigator-initiated, phase 2, two-stage single cohort trial evaluating avelumab with axitinib in recurrent or persistent EC. Participants must have MMR-P EC of any histology and have received at least one chemotherapeutic regimen, with no upper limit on the number of prior lines received. Prior use of immune checkpoint (IC) inhibitors is excluded. Treatment consists of avelumab 800mg IV every 2 weeks and axitinib 5mg orally twice daily. Co-primary endpoints are progression-free survival at 6 months (PFS6) and objective response rate by RECIST 1.1. Translational objectives include characterization of tumor-infiltrating lymphocytes, infiltrating myeloid cells, expression of IC markers, and whole exome sequencing to evaluate mutations in genes related to DNA repair and immunologic response. This is a two-stage design in the method of Sill et al, with 16 participants anticipated in stage 1 and 19 participants in stage 2, for a total of 35 participants. Accrual is ongoing. Clinical trial information: NCT02912572.

221 Background: ASCO’s Quality Oncology Practice Initiative (QOPI) includes process measures on oral chemotherapy education. Whether achievement of these measures has an impact on clinical outcomes and if an intervention to improve these measures can improve outcomes is not yet known. Methods: A retrospective analysis was conducted of patients initiated on oral chemotherapy in an academic medical center site and a community oncology practice between January 2016 and October 2019. The primary aim was to compare the time to emergency department (ED) within 90 days from initiation of oral chemotherapy of patients who met the QOPI process measure through an intervention of pharmacist-driven education with a comparison group of patients who had not received formal education. A secondary aim was to assess for a difference in oral chemotherapy medication persistence. Data were also analyzed by demographics, concurrent parenteral therapy, intent of therapy, and disease group. Results: 285 patients in the education group and 284 patients in the non-education group were analyzed. The education group had a higher proportion of patients with gastrointestinal and gynecologic cancers, and a lower proportion of patients with hematologic malignancies, compared to the non-education group. The education group also had a higher proportion of patients treated at the community practice compared to the non-education group. There was no statistical difference in median time-to-ED, with 49 days (IQR 37-74) in the education group and 59 days (IQR 41-60) in the non-education group (p=0.15). Conclusions: In patients receiving oral chemotherapy, pharmacist-driven education with improvement in QOPI process measures did not result in an improvement in time to ED. One factor contributing to this result may be that only 20% of patients required ED-level care within 90 days of starting oral We continue to collect data regarding medication persistence, which may be a more sensitive outcome measure. At this point, further work is needed to determine if achievement or modification of the QOPI oral chemotherapy process measures results in a clinically significant change in outcome. [Table: see text]

Precision oncology is now the evidence-based standard of care for the management of many advanced non-small cell lung cancers (NSCLCs). Expert consensus has defined minimum requirements for routine testing and identification of epidermal growth factor ( EGFR) mutations (15% of tumors harbor EGFR exon 19 deletions or exon 21 L858R substitutions) and anaplastic lymphoma kinase ( ALK) rearrangements (5% of tumors) in advanced lung adenocarcinomas (ACs). Application of palliative targeted therapies with oral tyrosine kinase inhibitors (TKIs) in advanced/metastatic lung ACs harboring abnormalities in EGFR (gefitinib, erlotinib, afatinib) and ALK/ ROS1/ MET (crizotinib) has consistently led to more favorable outcomes compared with traditional cytotoxic agents. In addition, mutations leading to resistance to first-line EGFR and ALK TKIs can now be successfully inhibited by soon to be approved third-generation EGFR TKIs (osimertinib, rociletinib) and second-generation ALK TKIs (ceritinib, alectinib). Notably, increasing feasibility, accessibility, and application of molecular profiling technologies has permitted dynamic growth in the identification of actionable driver oncogenes. Emerging genomic aberrations for which TKIs have shown impressive results in clinical trials and expansion of drug labels for approved agents are awaited include ROS1 rearrangements (1–2% of tumors, drug: crizotinib) and BRAF-V600E mutations (1–3% of tumors, drugs: vemurafenib, dafrafenib + trametinib). Evolving genomic events in which TKI responses have been reported in smaller series include MET exon 14 skipping mutations (2–4% of tumors, drug: crizotinib); high-level MET amplification (1–2% of tumors, drug: crizotinib); RET rearrangements (1% of tumors, drug: cabozantinib); and ERBB2 mutations (2–3% of tumors, drug: afatinib), among others. Unfortunately, the most common genomic event in NSCLC, KRAS mutations (25–30% of tumors), is not targetable with approved or in development small molecule inhibitors. Here, we review currently approved, emerging, and evolving systemic precision therapies matched with their driver oncogenes for the management of advanced NSCLC.

Oncologists are increasingly managing drug-induced pneumonitis in lung cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors. To date only few studies on the topic have described both radiologic and pathologic findings in these patients. Here, we report a fatal case of immune checkpoint inhibitor-associated pneumonitis initially presenting with an organizing pneumonia, but who rapidly developed acute respiratory distress syndrome (confirmed histologically at the time of autopsy). As such, this case illustrates the need for clinicians to maintain a high index of suspicion for immune checkpoint inhibitor associated pneumonitis and have a low threshold to perform CT imaging in any symptomatic patient receiving checkpoint inhibition therapy. CLINICAL PRACTICE POINTS.

Introduction Targeted somatic genomic analysis (EGFR, anaplastic lymphoma receptor tyrosine kinase gene [ALK], and ROS1) and programmed death ligand 1 (PD-L1) tumor proportion score (TPS) determined by immunohistochemistry (IHC) are used for selection of first-line therapies in advanced lung cancer; however, the frequency of overlap of these biomarkers in routine clinical practice is poorly reported. Methods We retrospectively probed the first 71 pairs of patients with lung adenocarcinoma from our institution. They were analyzed for PD-L1 by IHC using the clone 22C3 pharmDx kit (Agilent Technologies, Santa Clara, CA) and evaluated for co-occurrence of genomic aberrations and clinicopathologic characteristics. Results Surgical resection specimens, small biopsy (transbronchial or core needle) samples, and cytologic cell blocks (needle aspirates or pleural fluid) were tested. A PD-L1 TPS of at least ≥50% was seen in 29.6% of tumors. Of 19 tumors with EGFR mutations, ALK fluorescence in situ hybridization positivity, or ROS1 fluorescence in situ hybridization positivity, 18 had a PD-L1 TPS less than 50% versus only one tumor with a PD-L1 TPS of at least 50% (p = 0.0073). Tumors with a PD-L1 TPS of at least 50% were significantly associated with smoking status compared with tumors with a PD-L1 TPS less than 50% but were not associated with patient sex, ethnicity, tumor stage, biopsy site, or biopsy type/preparation. Conclusions PD-L1 IHC can be performed on routine clinical lung cancer specimens. A TPS of at least 50% seldom overlaps with presence of driver oncogenes with approved targeted therapies. Three biomarker-specified groups of advanced lung adenocarcinomas can now be defined, each paired with a specific palliative first-line systemic therapy of proven clinical benefit: (1) EGFR/ALK/ROS1-affected adenocarcinoma paired with a matched tyrosine kinase inhibitor (∼20% of cases), (2) PD-L1–enriched adenocarcinoma (TPS ≥50%) paired with anti–PD-1 pembrolizumab (∼30% of cases), and (3) biomarker-negative (i.e., EGFR/ALK/ROS1/PD-L1–negative) adenocarcinoma paired with platinum doublet chemotherapy with or without bevacizumab (∼50% of cases).

Paraneoplastic syndromes are rare, occurring in

e18007 Background: Patients on oral chemotherapy (OC) often lack consistent education and monitoring, risking toxicity and poor adherence. We developed an OC management program including education and an online tool for active outreach. Methods: In November 2017, we initiated pharmacist-led education for patients newly prescribed OC at a community practice and in the gastrointestinal oncology group at an academic medical center (AMC). An online tool assessing adherence, symptoms, and financial toxicity was emailed to patients three days after starting OC. Non-responders were contacted for phone interviews. A random sample of 28 patients newly started on OC at both sites before the intervention in 2017 was analyzed at baseline. A retrospective chart analysis was done to collect time to symptom assessment, identification and action. A report generated date of first emergency department (ED) visit or hospitalization within the AMC. We conducted a Mann Whitney U-Test, using a one-sided p value of 0.025 with Bonferroni correction. Results: Sixty-nine of 106 eligible patients (66%) received education, of whom 36 (52.1%) received the online tool, and 13 (36.1%) responded. There was a significant difference between the intervention and baseline median times to first new/worsening symptoms (p = 0.0105) but otherwise there were no outcome improvements. Eight of 23 patients who did not respond to the electronic tool were interviewed and indicated that their illness impeded their ability to check email (n = 2), and that they never check email (n = 2). Conclusions: This OC management program improved time to detect new/worsening symptoms and could potentially improve outcomes after further patient accrual. Future investigation should examine ways to improve patient responsiveness to electronic patient-reported symptom tools. [Table: see text]

e20617 Background: Pembrolizumab (P) administered every 3 weeks ± chemotherapy is a standard treatment option for advanced NSCLC. However, there have been no post-approval studies to determine the optimal frequency of administration or if longer intervals between administrations are effective. Methods: We conducted a retrospective review of patients with advanced NSCLC treated with P for at least 4 cycles at a single academic center (02/2016-12/2018). Patients received P-based regimens administered at a standard frequency (3 weeks ± 3 days, group A), ≥ 25% of total treatment cycles outside the standard frequency (group B), and < 25% of total treatment cycles outside the standard frequency (group C). We extracted demographic, tumor characteristic, treatment detail and outcomes data. Results: Of 84 P-treated patients, 43 (51%) were identified as receiving at least 4 cycles (groups A: 17, B: 10, C: 16). There were no significant differences in sex, stage at diagnosis, smoking status, tumor histology, driver oncogene mutations, PD-L1 expression, tumor mutation burden, line of therapy, performance status, or immune-related adverse events (irAEs). Patients in group A were more likely to receive P+chemotherapy (groups A: 41.2%, B: 10%, C: 6.3%; p = 0.03). The reasons for non-standard cycles were: patient-physician preference (65.4% patients), irAEs (15.4%), and non-irAE medical issues (42.3%). Time to treatment discontinuation was significantly longer in groups B & C receiving P-based therapy at longer non-standard intervals and with no statistically significant differences in overall survival. Conclusions: Our data, though limited by sample size and single institution design, shows that a significant proportion of patients receive P at extended intervals in routine clinical practice and with comparable outcomes as would be expected for those with advanced NSCLC receiving P at label-specified 3-week intervals. Given the durability of benefit seen in such patients, this requires confirmation in larger datasets and prospective trials so as to maximize patient experience and clinical outcomes while minimizing financial toxicity.

283 Background: Monitoring of toxicity and adherence is often lacking for patients recently started on oral chemotherapy. National guidelines recommend active outreach to patients within a week after treatment start. We developed an online tool to actively reach out to patients newly started on oral chemotherapy at one academic medical center and community practice. Methods: A multi-disciplinary team, including patients, developed an online oral chemotherapy adherence, symptom, and financial toxicity assessment tool within REDCap. We implemented this tool for new oral chemotherapy prescriptions in May 2018 in the gastrointestinal oncology group of an academic medical center and a general community practice. To quantify the impact of this tool on symptom management, we completed a retrospective analysis of patients receiving new oral chemotherapy prescriptions at these same sites, in the 13 months immediately preceding clinical implementation of the online tool, May 2017 to May 2018. Results: In the pre-intervention historical cohort (n = 58) the median time to first symptom assessment by a clinician was 7 days (range 1 – 41 days, SD 7 days), median time to identifying a new or worsening symptom was 10 days (range 1-55 days, SD 10 days), and median time to clinical action regarding a new or worsening symptom was 10 days (range 1-104, SD 20 days). Our first intervention patient used the online tool in May 2018 to report symptoms of “nausea and fatigue,” 4 days after starting oral chemotherapy. This resulted in an oncology clinical nurse calling the patient to review symptom management by phone. Conclusions: The median time to first symptom assessment in our historical control cohort is 7 days, with standard deviation of 7 days, suggesting potential room for improvement. Thus far, the online tool has been completed by one patient. Further data will be reported regarding the uptake of this tool, the tool’s impact on quality measures, and patient reported symptoms, adherence, and financial toxicity.