Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

Combining anti-VEGFR and anti-EGFR antibodies: Randomized phase II study of irinotecan and cetuximab with/without ramucirumab in second-line colorectal cancer:(ECOG-ACRIN E7208).

INTRODUCTION: Early studies showed promise of combined anti-EGFR plus anti-VEGF antibodies for advanced colorectal cancer (CRC), yet this was later rejected as toxic and ineffective in studies not selected for RAS status. We studied advanced KRAS wild-type CRC, as second-line treatment, using irinotecan-cetuximab (IC) with or without the anti-VEGFR antibody, ramucirumab (ICR). METHODS: Patients with one prior regimen including fluoropyrimidine, oxaliplatin and bevacizumab, with KRAS wild-type tumors, were stratified by ECOG PS, time since last chemotherapy and progression on oxaliplatin, to IC (180 and 500 mg/2 q2w), vs modified ICR (mICR) (150 and 400 mg/m2 plus 6 mg/kg respectively). 102 patients were compared for progression-free survival (PFS) as primary endpoint (85% power for 70% improvement in median PFS from 4.5 to 7.65 months). RESULTS: Of the 102 enrolled, 44 treated with IC and 45 with mICR were evaluable. Median PFS was 6.0 vs 9.2 months respectively (HR 0.75, p = .07, significant by study design for p < .128). Response rate was 23% vs 36% (p = .27) and disease-control rate (DCR) was 52% vs 73% (p = .05). Grade ≥3 toxicity was not equivalent. Overall survival was not significantly different at ∼19 months. CONCLUSION: Previous phase 3 trials without RAS genotyping, rejected combining anti-EGFR and anti-VEGF drugs. In this randomized multi-center phase 2 study for KRAS wild type CRC (all previously bevacizumab-treated) the addition of ramucirumab, to irinotecan and cetuximab improved PFS and DCR, showing the combination is feasible and effective here. Further phase 3 trials with appropriate patient-selection are required. (NCT01079780).

Oncologic drug repository programs in the United States: a review and comparison.

As cancer affects 40% of all Americans during their lifetime, the financial burden of cancer care represents a significant contribution towards the overall cost of health care in the United States. Cancer drug repository programs offer a unique solution for patients who have limited financial ability to access medications while reducing medical waste. We reviewed all state legislation in the United States regarding cancer drug repository programs. Five states have oral anticancer drug (OACD)-specific drug repository programs, while 28 states have generalized drug repository programs. Iowa's statewide, mail-order OACD repository program is the preeminent example of an effective and efficient program, which should be replicated across the country. Many states have passed legislation allowing for drug repository programs but have struggled to translate such legislation into active programs due to lack of funding and management. We offer recommendations across policy, manufacturing, institutional, health care professional, and patient domains in order provide optimal patient care.

A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms: Results from ECOG-ACRIN E1Z11.

PURPOSE: Aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS. PATIENTS AND METHODS: Postmenopausal women with stage I to III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972). RESULTS: Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS. CONCLUSIONS: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race.

Are We There Yet? - Alternating Chemotherapy Regimens in Pancreatic Cancer.

In the randomized phase 2 SEQUENCE trial in patients with metastatic pancreatic cancer, reported in this issue of NEJM Evidence, the authors compared therapy with alternating FOLFOX and nab-paclitaxel/gemcitabine chemotherapy versus standard-of-care, single-regimen nab-paclitaxel/gemcitabine therapy.1 They were testing the idea that because most tumor cells express both basal and classic markers, alternating treatment would target both cell populations and thus confer a survival benefit. The trial, which enrolled 157 patients, met the primary end point of an overall survival rate at 12 months of 55.3% in the alternating treatment group compared with 35.4% in the standard-of-care group.

An update on pharmacotherapies for colorectal cancer: 2023 and beyond.

INTRODUCTION: Colorectal cancer (CRC) is one of the most prevalent and lethal cancers worldwide. The treatment of metastatic colorectal cancer (mCRC) is difficult, and mCRC has a survival rate of only 13-17% compared with 70-90% in locoregional CRC. There is ongoing research effort on pharmacotherapy for CRC to improve the treatment outcome. AREAS COVERED: We reviewed the current literature and ongoing clinical trials on CRC pharmacotherapy, with a focus on targeted therapy based on the results of genetic testing. The pharmacotherapies covered in this article include novel agents targeting EGFR and EGFR-related pathways, agents targeting the VEGF pathway, immunotherapy options depending on the MMR/MSI status, and new therapies targeting genetic fusions such as NTRK. We also briefly discuss the value of next-generation sequencing (NGS) in treatment selection and response monitoring. EXPERT OPINION: We advocate for the early and routine use of NGS to genetically characterize CRC to assist with pharmacotherapy selection. Targeted therapy is a promising field of ongoing research and improves CRC treatment outcome.

Defining the Role of the Advanced Practice Provider Within the National Cancer Institute Community Oncology Research Program.

PURPOSE: Oncology advanced practice providers (APPs), including nurse practitioners, clinical nurse specialists, physician assistants, and clinical pharmacists, contribute significantly to quality cancer care. Understanding the research-related roles of APPs in the National Cancer Institute's (NCI) Community Oncology Research Program (NCORP) could lead to enhanced protocol development, trial conduct, and accrual. METHODS: The 2022 NCORP Landscape Assessment Survey asked two questions about the utilization and roles of APPs in the NCORP. RESULTS: A total of 271 practice groups completed the 2022 survey, with a response rate of 90%. Of the 259 nonpediatric exclusive practice groups analyzed in this study, 92% used APPs for clinical care activities and 73% used APPs for research activities. APPs most often provided clinical care for patients enrolled in trials (97%), followed by assistance with coordination (65%), presenting/explaining clinical trials (59%), screening patients (49%), ordering investigational drugs (37%), and consenting participants (24%). Some groups reported APPs as an enrolling investigator (18%) and/or participating in institutional oversight/selection of trials (15%). Only 5% of NCORP sites reported APPs as a site primary investigator for trials, and very few (3%) reported APPs participating in protocol development. CONCLUSION: Practice groups report involving APPs in clinical research within the NCORP network; however, opportunities for growth exists. As team-based care has enhanced clinical practice in oncology, this same approach can be used to enhance successful research. Suggested strategies include supporting APP research-related time, recognition, and education. The findings of this survey and subsequent recommendations may be applied to all adult oncology practices that participate in clinical research.

Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort.

Importance: Tissue-based next-generation sequencing (NGS) of solid tumors is the criterion standard for identifying somatic mutations that can be treated with National Comprehensive Cancer Network guideline-recommended targeted therapies. Sequencing of circulating tumor DNA (ctDNA) can also identify tumor-derived mutations, and there is increasing clinical evidence supporting ctDNA testing as a diagnostic tool. The clinical value of concurrent tissue and ctDNA profiling has not been formally assessed in a large, multicancer cohort from heterogeneous clinical settings. Objective: To evaluate whether patients concurrently tested with both tissue and ctDNA NGS testing have a higher rate of detection of guideline-based targeted mutations compared with tissue testing alone. Design, Setting, and Participants: This cohort study comprised 3209 patients who underwent sequencing between May 2020, and December 2022, within the deidentified, Tempus multimodal database, consisting of linked molecular and clinical data. Included patients had stage IV disease (non-small cell lung cancer, breast cancer, prostate cancer, or colorectal cancer) with sufficient tissue and blood sample quantities for analysis. Exposures: Received results from tissue and plasma ctDNA genomic profiling, with biopsies and blood draws occurring within 30 days of one another. Main Outcomes and Measures: Detection rates of guideline-based variants found uniquely by ctDNA and tissue profiling. Results: The cohort of 3209 patients (median age at diagnosis of stage IV disease, 65.3 years [2.5%-97.5% range, 43.3-83.3 years]) who underwent concurrent tissue and ctDNA testing included 1693 women (52.8%). Overall, 1448 patients (45.1%) had a guideline-based variant detected. Of these patients, 9.3% (135 of 1448) had variants uniquely detected by ctDNA profiling, and 24.2% (351 of 1448) had variants uniquely detected by solid-tissue testing. Although largely concordant with one another, differences in the identification of actionable variants by either assay varied according to cancer type, gene, variant, and ctDNA burden. Of 352 patients with breast cancer, 20.2% (71 of 352) with actionable variants had unique findings in ctDNA profiling results. Most of these unique, actionable variants (55.0% [55 of 100]) were found in ESR1, resulting in a 24.7% increase (23 of 93) in the identification of patients harboring an ESR1 mutation relative to tissue testing alone. Conclusions and Relevance: This study suggests that unique actionable biomarkers are detected by both concurrent tissue and ctDNA testing, with higher ctDNA identification among patients with breast cancer. Integration of concurrent NGS testing into the routine management of advanced solid cancers may expand the delivery of molecularly guided therapy and improve patient outcomes.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Ampullary Adenocarcinoma, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Ampullary cancers refer to tumors originating from the ampulla of Vater (the ampulla, the intraduodenal portion of the bile duct, and the intraduodenal portion of the pancreatic duct), while periampullary cancers may arise from locations encompassing the head of the pancreas, distal bile duct, duodenum, or ampulla of Vater. Ampullary cancers are rare gastrointestinal malignancies, and prognosis varies greatly based on factors such as patient age, TNM classification, differentiation grade, and treatment modality received. Systemic therapy is used in all stages of ampullary cancer, including neoadjuvant therapy, adjuvant therapy, and first-line or subsequent-line therapy for locally advanced, metastatic, and recurrent disease. Radiation therapy may be used in localized ampullary cancer, sometimes in combination with chemotherapy, but there is no high-level evidence to support its utility. Select tumors may be treated surgically. This article describes NCCN recommendations regarding management of ampullary adenocarcinoma.

Bevacizumab in Combination With Oxaliplatin, Fluorouracil, and Leucovorin (FOLFOX4) for Previously Treated Metastatic Colorectal Cancer: Results From the Eastern Cooperative Oncology Group Study E3200.

PURPOSE: Colorectal cancer is the second leading cause of cancer mortality in the United States. Antiangiogenic therapy with bevacizumab combined with chemotherapy improves survival in previously untreated metastatic colorectal cancer. This study was conducted to determine the effect of bevacizumab (at 10 mg/kg) on survival duration for oxaliplatin-based chemotherapy in patients with previously treated metastatic colorectal cancer. PATIENTS AND METHODS: Eight hundred twenty-nine metastatic colorectal cancer patients previously treated with a fluoropyrimidine and irinotecan were randomly assigned to one of three treatment groups: oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab; FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end point was overall survival, with additional determinations of progression-free survival, response, and toxicity. RESULTS: The median duration of survival for the group treated with FOLFOX4 and bevacizumab was 12.9 months compared with 10.8 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for death = 0.75; P = .0011), and 10.2 months for those treated with bevacizumab alone. The median progression-free survival for the group treated with FOLFOX4 in combination with bevacizumab was 7.3 months, compared with 4.7 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for progression = 0.61; P < .0001), and 2.7 months for those treated with bevacizumab alone. The corresponding overall response rates were 22.7%, 8.6%, and 3.3%, respectively (P < .0001 for FOLFOX4 with bevacizumab v FOLFOX4 comparison). Bevacizumab was associated with hypertension, bleeding, and vomiting. CONCLUSION: The addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival duration for patients with previously treated metastatic colorectal cancer.

Combination of pembrolizumab and pelareorep promotes anti-tumour immunity in advanced pancreatic adenocarcinoma (PDAC).

BACKGROUND: We previously reported activity of pelareorep, pembrolizumab and chemotherapy. Patients developed new T-cell clones and increased peripheral T-cell clonality, leading to an inflamed tumour. To evaluate a chemotherapy-free regimen, this study assesses if pelareorep and pembrolizumab has efficacy by inducing anti-tumour immunological changes (NCT03723915). METHODS: PDAC patients who progressed after first-line therapy, received iv pelareorep induction with pembrolizumab every 21-days. Primary objective is overall response rate. Secondary objectives included evaluation of immunological changes within tumour and blood. RESULTS: Clinical benefit rate (CBR) was 42% amongst 12 patients. One patient achieved partial response (PR) and four stable disease (SD). Seven progressed, deemed non-responders (NR). VDAC1 expression in peripheral CD8+ T cells was higher at baseline in CBR than NR but decreased in CBR upon treatment. On-treatment peripheral CD4+ Treg levels decreased in CBR but not in NR. Analysis of tumour demonstrated PD-L1+ cells touching CD8+ T cells, and NK cells were more abundant post-treatment vs. baseline. A higher intensity of PD-L1 in tumour infiltrates at baseline, particularly in CBR vs. NR. Finally, higher levels of soluble (s)IDO, sLag3, sPD-1 observed at baseline among NR vs. CBR. CONCLUSION: Pelareorep and pembrolizumab showed modest efficacy in unselected patients, although potential immune and metabolic biomarkers were identified to warrant further evaluation.

Baseline Quality of Life is a Strong and Independent Prognostic Factor for Overall Survival in Metastatic Colorectal Cancer.

BACKGROUND: Previous studies have established that higher baseline quality of life (QOL) scores are associated with improved survival in patients with metastatic colorectal cancer (mCRC). We examined the relationship between overall survival (OS) and baseline QOL. PATIENTS AND METHODS: A total of 1 247 patients with mCRC participating in N9741 (comparing bolus 5-FU/LV, irinotecan [IFL] vs infusional 5-FU/leucovorin [LV]/oxaliplatin [FOLFOX] vs. irinotecan/oxaliplatin [IROX]) provided data at baseline on overall QOL using a single-item linear analogue self-assessment (LASA) 0-100 point scale. The association of OS according to clinically deficient (defined as CD-QOL, score 0-50) vs not clinically deficient (nCD-QOL, score 51-100) baseline QOL scores was tested. A multivariable analysis using Cox proportional hazards modeling was performed to adjust for the effects of multiple baseline factors. An exploratory analysis was performed evaluating OS according to baseline QOL status among patients who did or did not receive second-line therapy. RESULTS: Baseline QOL was a strong predictor of OS for the whole cohort (CD-QOL vs nCD-QOL: 11.2 months vs 18.4 months, P < .0001), and in each arm IFL 12.4 vs 15.1 months, FOLFOX 11.1 months vs 20.6 months, and IROX 8.9 months vs 18.1 months. Baseline QOL was associated with baseline performance status (PS) (P < .0001). After adjusting for PS and treatment arm, baseline QOL was still associated with OS (P = .017). CONCLUSIONS: Baseline QOL is an independent prognostic factor for OS in patients with mCRC. The demonstration that patient-assessed QOL and PS are independent prognostic indicators suggests that these assessments provide important complementary prognostic information.

Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.

Paclitaxel With or Without Cixutumumab as Second-Line Treatment of Metastatic Esophageal or Gastroesophageal Junction Cancer: A Randomized Phase II ECOG-ACRIN Trial.

BACKGROUND: Patients with advanced esophageal cancer carry poor prognoses; limited data exist to guide second-line therapy in the metastatic setting. Paclitaxel has been used yet is associated with limited efficacy. There is preclinical evidence of synergy between paclitaxel and cixutumumab, a monoclonal antibody targeting insulin-like growth factor-1 receptor. We conducted a randomized phase II trial of paclitaxel (arm A) versus paclitaxel plus cixutumumab (arm B) in the second-line for patients with metastatic esophageal or gastroesophageal junction (GEJ) cancers. METHODS: The primary endpoint was progression-free survival (PFS); 87 patients (43 in arm A, 44 in arm B) were treated. RESULTS: Median PFS was 2.6 months in arm A [90% CL 1.8-3.5] and 2.3 months in arm B [90% 2.0-3.5], P = .86. Stable disease was observed in 29 (33%) patients. Objective response rates for Arms A and B were 12% [90% CI, 5-23%] and 14% [90% CI, 6-25%]. Median overall survival was 6.7 months [90% CL 4.9-9.5] in arm A and 7.2 months [90% CL 4.9-8.1] in arm B, P = 56. CONCLUSION: The addition of cixutumumab to paclitaxel in second-line therapy of metastatic esophageal/GEJ cancer was well tolerated but did not improve clinical outcomes relative to standard of care (ClinicalTrials.gov Identifier: NCT01142388).

An Assessment of the Feasibility and Utility of an ACCC-ASCO Implicit Bias Training Program to Enhance Racial and Ethnic Diversity in Cancer Clinical Trials.

PURPOSE: Cancer trial participants do not reflect the racial and ethnic diversity in the population of people with cancer in the United States. As a result of multiple system-, patient-, and provider-level factors, including implicit bias, cancer clinical trials are not consistently offered to all potentially eligible patients. MATERIALS AND METHODS: ASCO and ACCC evaluated the utility (pre- and post-test knowledge changes) and feasibility (completion rates, curriculum satisfaction metrics, survey questions, and interviews) of a customized online training program combined with facilitated peer-to-peer discussion designed to help research teams identify their own implicit biases and develop strategies to mitigate them. Discussion focused on (1) specific elements of the training modules; (2) how to apply lessons learned; and (3) key considerations for developing a facilitation guide to support peer-to-peer discussions in cancer clinical research settings. We evaluated discussion via a qualitative assessment. RESULTS: Participant completion rate was high: 49 of 50 participating cancer programs completed training; 126 of 129 participating individuals completed the training (98% response rate); and 119 completed the training and evaluations (92% response rate). Training increased the mean percentage change in knowledge scores by 19%-45% across key concepts (eg, causes of health disparities) and increased the mean percentage change in knowledge scores by 10%-31% about strategies/actions to address implicit bias and diversity concerns in cancer clinical trials. Knowledge increases were sustained at 6 weeks. Qualitative evaluation validated the utility and feasibility of facilitated peer-to-peer discussion. CONCLUSION: The pilot implementation of the training program demonstrated excellent utility and feasibility. Our evaluation affirms that an online training designed to raise awareness about implicit bias and develop strategies to mitigate biases among cancer research teams is feasible and can be readily implemented in cancer research settings.

Treatment of Metastatic Colorectal Cancer: ASCO Guideline.

PURPOSE: To develop recommendations for treatment of patients with metastatic colorectal cancer (mCRC). METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS: Five systematic reviews and 10 randomized controlled trials met the systematic review inclusion criteria. RECOMMENDATIONS: Doublet chemotherapy should be offered, or triplet therapy may be offered to patients with previously untreated, initially unresectable mCRC, on the basis of included studies of chemotherapy in combination with anti-vascular endothelial growth factor antibodies. In the first-line setting, pembrolizumab is recommended for patients with mCRC and microsatellite instability-high or deficient mismatch repair tumors; chemotherapy and anti-epidermal growth factor receptor therapy is recommended for microsatellite stable or proficient mismatch repair left-sided treatment-naive RAS wild-type mCRC; chemotherapy and anti-vascular endothelial growth factor therapy is recommended for microsatellite stable or proficient mismatch repair RAS wild-type right-sided mCRC. Encorafenib plus cetuximab is recommended for patients with previously treated BRAF V600E-mutant mCRC that has progressed after at least one previous line of therapy. Cytoreductive surgery plus systemic chemotherapy may be recommended for selected patients with colorectal peritoneal metastases; however, the addition of hyperthermic intraperitoneal chemotherapy is not recommended. Stereotactic body radiation therapy may be recommended following systemic therapy for patients with oligometastases of the liver who are not considered candidates for resection. Selective internal radiation therapy is not routinely recommended for patients with unilobar or bilobar metastases of the liver. Perioperative chemotherapy or surgery alone should be offered to patients with mCRC who are candidates for potentially curative resection of liver metastases. Multidisciplinary team management and shared decision making are recommended. Qualifying statements with further details related to implementation of guideline recommendations are also included.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Resource and Reimbursement Barriers to Comprehensive Cancer Care Delivery: An Analysis of Association of Community Cancer Centers Survey Data.

PURPOSE: Comprehensive cancer care (CCC) delivery is recommended in guidelines and considered essential for high-quality cancer management. Barriers, such as insufficient reimbursement, prevent consistent access to and delivery of CCC. Association of Community Cancer Centers conducted a national survey to elucidate capacity and barriers to CCC delivery to inform policy and value-based payment reform. METHODS: Survey methodology included item generation with expert review, iterative piloting, and cognitive validity testing. In the final instrument, 27 supportive oncology services were assessed for availability, reasons not offered, and coverage/reimbursement. RESULTS: 204 of 704 member programs completed survey questions. Despite most services being reported as offered, a minority were funded through insurance reimbursement. The services least likely to obtain reimbursement were those that address practical and family/childcare needs (0.7%), caregiver support (1.5%), advanced care directives (1.7%), spiritual services (1.8%), and navigation (2.7%). These findings did not vary by region or practice type. CONCLUSION: There is a lack of sufficient reimbursement, staffing, and budget to provide CCC across the United States. Care models and reimbursement policies must include CCC services to optimize delivery of cancer care.

Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211).

PURPOSE: Patients with advanced pancreatic neuroendocrine tumors (NETs) have few treatment options that yield objective responses. Retrospective and small prospective studies suggest that capecitabine and temozolomide are associated with high response rates (RRs) and long progression-free survival (PFS). PATIENTS AND METHODS: E2211 was a multicenter, randomized, phase II trial comparing temozolomide versus capecitabine/temozolomide in patients with advanced low-grade or intermediate-grade pancreatic NETs. Key eligibility criteria included progression within the preceding 12 months and no prior temozolomide, dimethyl-triazeno-imidazole-carboxamide or dacarbazine, capecitabine or fluorouracil. The primary end point was PFS; secondary endpoints were overall survival, RR, safety, and methylguanine methyltransferase (MGMT) by immunohistochemistry and promoter methylation. RESULTS: A total of 144 patients were enrolled between April 2013 and March 2016 to temozolomide (n = 72) or capecitabine and temozolomide (n = 72); the primary analysis population included 133 eligible patients. At the scheduled interim analysis in January 2018, the median PFS was 14.4 months for temozolomide versus 22.7 months for capecitabine/temozolomide (hazard ratio = 0.58), which was sufficient to reject the null hypothesis for the primary end point (stratified log-rank P = .022). In the final analysis (May 2021), the median overall survival was 53.8 months for temozolomide and 58.7 months for capecitabine/temozolomide (hazard ratio = 0.82, P = .42). MGMT deficiency was associated with response. CONCLUSION: The combination of capecitabine/temozolomide was associated with a significant improvement in PFS compared with temozolomide alone in patients with advanced pancreatic NETs. The median PFS and RR observed with capecitabine/temozolomide are the highest reported in a randomized study for pancreatic NETs. MGMT deficiency was associated with response, and although routine MGMT testing is not recommended, it can be considered for select patients in need of objective response (ClinicalTrials.gov identifier: NCT01824875).