ASCO Guidelines Research Articles

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update Clinical Insights.

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update Clinical Insights.

Endocrine and Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer-Capivasertib-Fulvestrant: ASCO Rapid Recommendation Update.

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).

2020 ASCO, 2023 NCCN, 2023 MASCC/ESMO, and 2019 CCO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in cancer patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common toxicity that may impair the quality of life of patients with various malignancies ranging from early to end stages. In light of frequent changes to the guidelines for optimal management of CINV, we undertook this narrative review to compare the most recent guidelines published by ASCO (2020), NCCN (2023), MASCC/ESMO (2023), and CCO (2019). The processes undertaken by each organization to evaluate existing literature were also described. Although ASCO, NCCN, MASCC/ESMO, and CCO guidelines for the treatment and prevention of CINV share many fundamental similarities, the literature surrounding low and minimal emetic risk regimens is lacking. Current data regarding adherence to these guidelines is poor and warrants further investigation to improve care.

Vaccination of Adults With Cancer: ASCO Guideline.

To guide the vaccination of adults with solid tumors or hematologic malignancies. A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and nonrandomized studies on the efficacy and safety of vaccines used by adults with cancer or their household contacts. This review builds on a 2013 guideline by the Infectious Disease Society of America. PubMed and the Cochrane Library were searched from January 1, 2013, to February 16, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. A total of 102 publications were included in the systematic review: 24 systematic reviews, 14 RCTs, and 64 nonrandomized studies. The largest body of evidence addressed COVID-19 vaccines. The goal of vaccination is to limit the severity of infection and prevent infection where feasible. Optimizing vaccination status should be considered a key element in the care of patients with cancer. This approach includes the documentation of vaccination status at the time of the first patient visit; timely provision of recommended vaccines; and appropriate revaccination after hematopoietic stem-cell transplantation, chimeric antigen receptor T-cell therapy, or B-cell-depleting therapy. Active interaction and coordination among healthcare providers, including primary care practitioners, pharmacists, and nursing team members, are needed. Vaccination of household contacts will enhance protection for patients with cancer. Some vaccination and revaccination plans for patients with cancer may be affected by the underlying immune status and the anticancer therapy received. As a result, vaccine strategies may differ from the vaccine recommendations for the general healthy adult population vaccine.Additional information is available at www.asco.org/supportive-care-guidelines.

Vaccination of Adults With Cancer: ASCO Guideline Clinical Insights.

Vaccination of Adults With Cancer: ASCO Guideline Clinical Insights.

Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline Q&A.

@JCO_ASCO guideline on #cannabis in cancer with @JCOOP_ASCO companion Q&A addressing key clinical questions.

Follow-up of breast cancer: why is it necessary to start a Consensus in 2024?

In Italy, breast cancer is the most frequently diagnosed cancer in women, with 55,900 new cases in 2023 (over 90% in the early stages). Due to the screening, early diagnosis and adjuvant treatment, these patients have a 5-years survival rate of 87% after the diagnosis. There are 834,154 women in Italy with a previous diagnosis of breast cancer: most of these women require a follow-up. The AIOM, ESMO and ASCO Guidelines recommend for early breast cancer (EBC) a clinical follow-up with only physical examination (and eliciting of symptoms) and an annual X-ray mammography, on the basis of the results of two randomized trials published in 1994 that showed no benefit in overall survival with intensive follow-up. However, an Italian survey reported the application by 80% of oncologists of an intensive follow-up based on the individual patient’s risk of recurrence. In fact, the oncologists believe that an early diagnosis of locoregional or distant recurrence may allow an early start of very effective therapies. In this lack of up-to-date scientific data, many questions about follow-up remain unanswered and the few ongoing studies will provide results in several years. Non-compliance with guideline recommendations leads to increased costs for the healthcare system. Furthermore, management varies widely from centre to centre with regard to guideline recommendations, resulting in inequalities between patients. For these reasons, the follow-up of breast cancer should be reconsidered. In the absence of recent scientific evidence, a multidisciplinary group of breast cancer experts has initiated a Consensus on the follow-up of EBC according to the mini-Delphi methodology. The project will be completed by the end of 2024.

Role of thromboprophylaxis during neoadjuvant chemotherapy before radical cystectomy in patients with bladder cancer: Results of a multicenter retrospective cohort study.

598 Background: Patients undergoing radical cystectomy are at risk of developing venous thromboembolic events (VTE), with most VTEs occurring during neoadjuvant chemotherapy. The ASCO Clinical Practice Guideline Update recommends thromboprophylaxis in cancer patients with a high risk of VTE and a low risk of bleeding. However, the risks of VTE and bleeding with or without thromboprophylaxis in bladder cancer patients scheduled for radical cystectomy have not been well evaluated. Methods: We conducted a retrospective cohort study of patients with non-metastatic bladder cancer undergoing cystectomy across 28 centers in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis during neoadjuvant chemotherapy on VTE and bleeding. Results: Of 4886 patients, 4631 (95%) received neither thromboprophylaxis nor anticoagulation during chemotherapy. Thromboprophylaxis during neoadjuvant chemotherapy was prescribed in 151 (3%) patients mainly being enoxaparin (80%) with a median duration of 94 (range 38 to 104) days. In inverse probability weighting analyses, patients with thromboprophylaxis compared to patients without thromboprophylaxis during chemotherapy had not only a lower VTE (HR 0.32 [95% CI, 0.12 to 0.81], p-value = 0.016) but also a lower bleeding risk (HR 0.03 [95% CI, 0.09 to 0.12], p-value: <0.0001). Conclusions: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomized trials in other malignancies. Our data suggests thromboprophylaxis seems protective against VTEs during neoadjuvant chemotherapy in bladder cancer patients planned for cystectomy. The ASCO guidelines recommending thromboprophylaxis during chemotherapy should therefore also be regarded as a standard of care in patients treated with neoadjuvant chemotherapy before cystectomy.

Germline testing in patients with early-onset pancreatic cancer (EOPC).

639 Background: EOPC, defined as pancreatic cancer (PC) diagnosed at 60 years of age or younger, is associated with significant life years lost. Approximately 5-10% of average-onset PC have an underlying germline etiology. Currently NCCN & ASCO guidelines recommend germline testing in all pts w PC. However, there is limited data regarding to what extent pts with EOPC pursue recommended germline testing. We examined the findings from genetic evaluation in EOPC. Methods: A retrospective review of EOPC pts at the Levine Cancer Institute who underwent clinical genetic assessment between January 2019 and December 2021 was performed. Data on clinicodemographic, family history, and genetic testing results were obtained and analyzed descriptively. Results: We identified 69 EOPC pts who were evaluated by genetics. Baseline characteristics include median age of 55 years (range 25-60) with 52% male, 48% white, 23% black, and 52% with current or prior tobacco use. At presentation, 41% and 59% had metastatic and non-metastatic disease, respectively. Eight (12%) pts declined germline testing. Among the 61 who underwent germline testing, 30 (49%) pts had negative testing, 21 (34%) had only variants of uncertain significance, and 10 (16%) had pathogenic/likely pathogenic germline variants (PVs). The most frequently seen PVs were ATM (20%), BRCA1 (20%), BRCA2 (10%), MLH1 (10%), NTHL1 (10%), PTCH1 (10%), CFTR (10%) and one (10%) with multiple pathogenic germline findings including RAD51 and BRCA1. Among the 10 pts with PVs, only two reported any first or second-degree family members with cancer. Conclusions: In this cohort of EOPC at a large community multi-site cancer center, 16% of patients had germline PVs, higher than reported in older patients with PC. Only 20% of pts w PVs reported first or second-degree family members with cancer and highlights the importance to recommend germline testing independent of family history even among EOPC cohorts. Further investigation to clarify reasons for refusal of germline testing in EOPC should be evaluated.

Early Recognition and Management of Side Effects Related to Systemic Anticancer Therapy for Advanced Breast Cancer

ObjectivesAdvances in science and technology have meant there are numerous treatment options available for people with advanced breast cancer (ABC). However, each therapeutic approach can cause side effects or adverse events, which can significantly affect the person's quality of life, overall well-being, and, in some instances, safety. This report presents an overview of the common side effects of systemic anticancer therapy and ways to manage them. Data SourcesData sources include peer-reviewed articles sourced in electronic databases and national and international best practice guidelines (ESMO, ASCO, and MASCC guidelines). ConclusionSystemic anticancer therapies have side effects that healthcare professionals need to know about to monitor and manage them in early stages. Nurses play an important role in patient education, early identification, monitoring, and management of treatment side effects. Implications for Nursing PracticePeople with ABC face many challenges during their treatment journey. Oncology nurses, specialist nurses, and nurse practitioners can be of support by providing preventive measures and side effects management at an early stage. Nurses need to have a good understanding of toxicity management but also advanced tumor-specific cancer knowledge of the different subtypes of ABC and holistic assessment skills. They are also key to providing support and enhancing self-management and early recognition of side effects.

Diagnosis Update and Treatment of Depression in Breast Cancer Survivor

Individuals suffering from breast cancer or those who have overcome it may experience symptoms such as despondency, despair, apprehension, and a feeling of void. The aim of this study is to provide a comprehensive overview of the diagnosis and treatment advancements for depression in people who have been diagnosed with and survived breast cancer. The prevalence of depressive symptoms and their association with patients' and survivors' quality of life were assessed using the Patient Health Questionnaire (PHQ-8). Depression has a robust association with quality of life. Several clinical care guidelines for cancer patients with co-morbid distress have highlighted the importance of screening and detection. According to the ASCO guidelines, healthcare facilities should create networks of referral sources or appropriate resources to efficiently handle patients' concerns about screening measures, in addition to doing screenings. The availability of screening or treatment depends directly on the financial resources of the institutions that provide them. Ultimately, due to the continuous advancements in breast cancer treatments, a significant number of individuals who have survived breast cancer will need prompt intervention to manage the long-term consequences of the illness. Survivors of breast cancer nevertheless encounter a significant health hazard in the form of depression, which endures long after the completion of therapy.

Systemic Therapy for Melanoma: ASCO Guideline Update Q and A.

This Q&A answers questions regarding ASCO's recent Systemic Therapy for Melanoma guideline.

Assessment of Incidence of Distress and Utilization of Supportive Care Services in Multiple Myeloma Patients, a Retrospective Single Center Experience

Introduction: Multiple myeloma (MM) is the second most common hematological malignancy. Current literature represents substantial underutilization of guideline-recommended supportive services (SS) in MM patients. Earlier studies have shown that most patients with MM have focal osseous lesions leading to skeletal-related events, fractures, pain, and debility. These events may negatively affect the treatment course and result in poor quality of life. Recent NCCN and ASCO guidelines recommend utilization of SS in all patients by early integration of cancer care for symptom control while being treated for primary malignancy. We evaluated the level of distress in patients (pts), SS utilization, ED visits, and hospitalization in pts with MM. Methods: We included adult patients (≥18 years) with newly diagnosed or relapsed/refractory MM at Levine Cancer Institute who had completed an electronic distress survey (EDS) within three months of diagnosis or relapse. Amyloidosis and plasma cell leukemia diagnoses were excluded. The EDS includes questions related to sociodemographic, patient-reported outcomes (PROs): distress level, physical symptoms (scale 0 - 10), screening for depression (PHQ-2, scale 0 - 6), anxiety (GAD-2, scale 0 - 6),Utilization of at least one SS (social work, palliative medicine, psych-oncology, cancer rehab, integrative medicine, and nutrition) within 6 months of EDS and emergency department visits/hospitalizations within 1 year of EDS were collected, retrospectively, from the electronic medical record. The PROs were summarized overall and compared among three distress groups [Distress score (DS) <4, 4-6, ≥7] with Wilcoxon rank sum tests for the EDS symptom scores and Fisher's exact tests for other categorical endpoints. Results: 541 MM pts were identified with an EDS within 3 months of diagnosis or relapse (assessment date range: January 2017 - May 2022), with 71.5% of those occurring near diagnosis, and 28.5% occurring around relapse. The mean age was 64.9 years, 58.6% were male, and additional patient characteristics are presented in Table 1. There were 33.8% (n=183) pts with DS<4, 30.9% (167) with DS 4-6, and 35.3% (191) with DS of ≥7. The highest scoring EDS symptoms were pain (mean score 4.7), fatigue (5.1) and sleep disturbance (3.6). Broadly, patients with higher distress scores had higher symptom scores (p<0.05 for all symptoms). There were 77.6% (420) pts with anxiety GAD-2 score of 0-2, 12.9% (70) pts with a score of 3-4 and 9.4% (51) pts with a score of 5-6. Similarly, for depression, 76.9% (416) pts reported a PHQ-2 score of 0-2, 15% (81) with a score of 3-4, and 8.1% (44) with a score of 5-6. For anxiety and depression, patients with higher DS had higher depression and anxiety screening scores (p <0.001), as shown in Table 2. 64.3% (348) pts utilized at least one SS within six months of their initial EDS assessment. The rate of utilization of at least one SS increased with DS (49.2% in DS <4, 67.1% in DS 4-6, and 76.7% in DS ≥7; p value<0.001). Numerically, more patients with high distress had at least one ED visit within a year of EDS (25.7% DS <4, 33.5% DS 4-6, 36.1% DS ≥7, p = 0.08). There was no significant difference in hospitalization within 1 year between the DS groups. There were 147 (36.8%) pts with high-risk cytogenetics, of which 43.5% had a distress score of ≥7. The rate of utilization of SS, ED visits, and hospitalizations was numerically higher in pts with newly diagnosed MM (68.5%, 34.4%, 63.1%, respectively), as compared to pts with RRMM (64.3%, 25.3%, 48.7%). Conclusion: The disease-specific symptoms predict clinically significant DS >4 on EDS. There were about 20% of pts with screening score >2 for anxiety (GAD-2) & depression (PHQ-2) that may warrant further exploration regarding the detail and nature of symptoms related to the diagnosis. There was a higher rate of utilization of SS and ED visits in pts with higher DS. Given these findings, there is a need to identify the optimal healthcare pathways for better utilization & incorporation of these EDS and PROs in the clinical care of distressed patients. Our study indicates that more work is needed to align needs with resources in order to optimize quality of life and disease outcomes for our pts.

Incidence and treatment of checkpoint inhibitor induced immune related adverse events in the emergency department.

438 Background: Immune checkpoint inhibitors (ICPis) are currently indicated for the treatment of various types of cancers. Through inhibition of the cancer cell’s checkpoint mediated T-cell evasion, ICPis allow for sustained T-cell activation and proliferation, resulting in increased cancer cell death. However, due to increased activation and proliferation of cytotoxic T-cells, ICPis have been associated with a wide spectrum of adverse effects, known as immune related adverse effects (irAEs). Although recently updated, the 2018 NCCN and ASCO guidelines state that treatment is based on the location and severity of irAEs. In general, grade 3 toxicities warrant suspension of ICPis and initiation of high-dose corticosteroids. Corticosteroids should then be tapered over the course of at least 4-6 weeks. The diagnosis of an irAE is challenging, toxicities may be misdiagnosed as there is a diverse familiarity with ICPis and their associated irAEs. Subsequently, care may be delayed, and patients may not receive appropriate guideline directed care. Methods: This multi-center chart review included 7 hospitals within a large health system. Our electronic health record was utilized to compile a report of patients who had received ICPIs within 12 months of presentation to an ED within the health system between 9/1/2019 and 9/1/2022. Assessed outcomes included incidence and type of irAE, time between last ICPi dose and presentation to the ED, steroid used for treatment, time to steroid, treatment driver, and the action that deviated from the 2018 ASCO/NCCN guideline directed treatment if applicable. Results: Of the 241 patients receiving an ICPi, 26 (10.8%) experienced an irAE that prompted a visit to an ED within our health system. Guideline directed treatment of irAE(s) was followed 76.9% of the time, with the steroid dose being too low (15.4%) and the steroid taper occurring too quickly (7.7%) being the two reasons for discordant treatment. Treatment started a median of 1.1 after presentation to an ED, with colitis as the most prevalent irAE in 11 patients (42%) presenting. For all patients, there was an average of 20 days between the last ICPi dose and presentation to ED. The main steroid used was methylprednisolone (42%). Conclusions: The 10.8% of patients who experienced an irAE that prompted a visit to an ED within our health system is a lower rate than what has been described in the literature previously, where rates of presentation to an ED due to an irAE ranged from 25-37%. This could be due to previous data coming from before or shortly after the publication of ASCO and NCCN guidelines in 2018, or because our outpatient medical staff has become more aware of irAEs and their appropriate treatment. Limitations include this review was retrospective, no patients had an irAE that was refractory to steroids, and the study period being soon after national guidelines were published.

Care utilization and satisfaction among patients with cancer with neutropenic fever managed by a remote patient monitoring (RPM) program.

572 Background: The DEFeNDR (Decreasing the burden of Febrile Neutropenia through Dynamic RPM) program leverages in-home technology and centralized nurse monitoring to facilitate ambulatory management as an alternative to hospital-based care for cancer patients with neutropenic fever (NF). The objective of this study is to assess 30-day care utilization outcomes and patient satisfaction at 12 months after program implementation. Methods: Adult cancer patients hospitalized with NF were assessed daily for DEFeNDR program eligibility including MASCC score ≥21 (per ASCO guidelines) and no cellular therapy (CAR-T, BMT) in the prior 100 days. Patients agreeing to participate in the 30-day program received a cellular-enabled tablet with pre-connected devices for twice-daily vital signs and symptom assessments. Patient generated data were EHR-integrated in real-time. Embedded decision trees facilitated alerts for adverse trends. Virtual RPM nurses responded to alerts and utilized predefined care pathways. The primary endpoint was the mean proportion of evaluable days spent inpatient (mPEDI) within 30 days of eligibility comparing those who participated in the program (RPM) with those who declined (no RPM). Results: Of 85 eligible patients, 62 were offered DEFeNDR participation. Of those, 34 (54.8%) participated and 28 (45.2%) declined. Baseline characteristics and care utilization outcomes are summarized in Table 1. RPM patients experienced significantly lower mPEDI compared with unmonitored patients [5.1% (Standard Error [SE], 1.9%) vs 12.4% (SE, 2.1%); Wilcoxon Rank Sums p-value, 0.032]. RPM patients also experienced a trend toward fewer total hospital days and lower 30-day readmission rate, as well as shorter mean length of stay and lower rate of ICU utilization when readmitted. Non-visit care activities (EHR clinical communications, documentation, and patient messaging) were decreased from pre-hospital baseline for 58.8% of RPM patients versus 46.6% of those unmonitored. All RPM patients completing a patient satisfaction survey (n=9) indicated that they would recommend the program to patients with a similar condition. Conclusions: Cancer patients with NF participating in the DEFeNDR program experienced a significant reduction in mPEDI and care utilization compared with those who declined. Further studies are warranted to assess comparative effectiveness of this model vs usual care.[Table: see text]

Simultaneous care clinic: A mono-institutional experience at an ESMO designated center for palliative care.

254 Background: Early palliative care has been shown to improve patient (pts) and caregiver satisfaction, symptom control, quality of end-of-life care, cost and in some cases survival in pts with advanced cancer. In accordance with ASCO, ESMO and AIOM guidelines a Simultaneous Care Clinic (SCC) was set up at Veneto Institute of Oncology (IOV) since 2014. In the Castelfranco Branch of the IOV, SCC started in January 2022. Methods: Data from all consecutive outpatient patients seen in SCC were retrieved from a prospectively maintained database.Data collected included cancer type, status of disease, performance status (PS), ongoing oncological treatment, nutritional evaluation, social evaluation, psychological evaluation, activation of home territorial and/or palliative care services,use of other health services after a first visit and place of death. At the first visit pts were evaluated with validated tools for symptom identification, Edmonton Symptom Assessment (ESAS), distress thermometer, Malnutrition Universal Screening Toll (MUST). Results: From January to December 2022seventy-four pts were evaluated by a multidisciplinary team and re-evaluated 2 months later in terms of improvement or stabilization of symptoms, appropriateness of intervention and outcome. All patients had a metastatic disease and were in active oncological treatment. The median age was 73 y and the most prevalent disease type was gastrointestinal cancers (48%). The median time from first SCC visit to death was 3.8 months; 32 pts are still alive. At the first visit symptom management measures were adopted. The median score for the distress thermometer was 5 with higher prevalence of physical problem. A higher prevalence on 7-10 ESAS score (26% of the pts) was found for pain, fatigue and lack of appetite. At the second visit, an improvement was observed: the median score for the distress thermometer was 4 and ESAS score was 7-10 in 18% of the pts. At first SCC visit, patients deemed in need of home care services were 17 (23%) and for these a formal request for Home Care services activation was sent to the Local Health Territorial Unit (Distretto ULSS). Conclusions: The SCC multidisciplinary assessment represents an organizational model effective in granting a global management of needs with the aim of improving the therapeutic path for patients and their caregivers.

Current and Emerging Role of Monoclonal Antibody-Based First-Line Treatment in Advanced Gastro-Esophageal and Gastric Cancer.

Gastric cancer is the fifth most common malignancy worldwide and one of the main causes of cancer-related death. While surgical treatment is the only curative option for early disease, many have inoperable or advanced disease at diagnosis. Treatment in this case would be a combination of chemotherapy and immunotherapy. Gastro-esophageal (GEJ) and gastric cancer (GC) genetic profiling with current molecular diagnostic techniques has significantly changed the therapeutic landscape in advanced cancers. The identification of key players in GEJ and GC survival and proliferation, such as human epidermal growth factor 2 (HER2), vascular endothelial growth factor (VEGF), and programmed cell death protein 1 (PD-1)/programmed cell death ligand-1 (PD-L1), has allowed for the individualization of advanced cancer treatment and significant improvement in overall survival and progression-free survival of patients. This review comprehensively examines the current and emerging role of monoclonal antibody-based first-line treatments in advanced GEJ and GC. We explore the impact of monoclonal antibodies targeting HER2, VEGF, PD-1/PD-L1, and Claudin 18.2 (CLDN18.2) on the first-line treatment landscape by talking about key clinical trials. This review emphasizes the importance of biomarker testing for optimal treatment selection and provides practical recommendations based on ASCO guidelines.

Management of Metastatic Renal Clear Cell Cancer: ASCO Guideline Rapid Recommendation Update.

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. See the Appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).

Systemic Therapy for Tumor Control in Well-Differentiated Metastatic Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline Q and A.

ASCO recently published new guidance on systemic therapy for tumor control in well-differentiated metastatic gastrointestinal and pancreatic neuroendocrine tumors in the Journal of Clinical Oncology. A companion Q and A article in the JCO-OP addresses some of the questions that clinicians may face as they implement these recommendations into clinical practice, including the role of somatostatin receptors and observation, definition of terms used within the guideline, considerations related to therapy options for G3 NETs, and future direction in research and treatment. ASCO also plans to address recommendations on the topic of symptom control of GEP-NETs in a forthcoming guideline

Systemic Therapy for Tumor Control in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline.

To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. Eight randomized controlled trials met the inclusion criteria for the systematic review. Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)-positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.