CONTEXT:Pediatric death can lead to long-term adverse effects on parents' health. OBJECTIVES:To describe the trajectory of parental mental and physical health burden within 24 months before and after a child's death and to evaluate the impact of specialized pediatric palliative care (SPPC) and several a priori selected factors on new mental or physical health burden in bereaved parents within 12 months following the death of a child. METHODS:Retrospective cohort study of biological parents of children (0-21 years) who died in or out of the hospital within six months of receiving care in the intensive care units (ICUs) of a free-standing quaternary care children's hospital in the Mountain West region between January 2013 and December 2019. Parental mental and physical health burden were assessed within 24 months before and after a child's death in six-month intervals. Multivariable logistic regression models evaluated the associations between new parental health burden within 12 months following a child's death with SPPC consultation and several a priori factors. RESULTS:Of 776 deceased children linked to 773 mothers and 711 fathers, 36.1% received a SPPC consultation prior to death. Higher rates of mental and physical health burden were observed in mothers than fathers across all time points. Lack of SPPC was associated with increased risks for new mental and physical health burden for mothers within 12 months after the child's death (adjusted odds ratios [95% CIs] 1.77 [1.03-3.03] and 2.63 [1.07-6.46], respectively). CONCLUSIONS:Bereaved parents, especially mothers, experienced new mental and physical health burden up to 24 months after a child's death. SPPC may be helpful in reducing the development of new health burdens in mothers within 12 months after a child's death.

Introduction:Patients with congenital heart disease are medically complex and experience high rates of morbidity and mortality. Pediatric palliative care (PPC) supports families navigating complex medical scenarios. This study evaluates the effect of quality improvement (QI) interventions towards increasing PPC consultations in patients with heart disease and cardiac intensive care unit (CICU) length of stay (LOS) >= 14 days. Methods:We conducted a mixed methods QI study using CICU team members and family survey assessments of PPC involvement. Patients with CICU LOS >= 14 days were eligible and comprised our study cohort. Interventions included the implementation of a digital prompt screening for eligible patients sent to CICU and PPC providers, as well as the implementation of weekly huddles to discuss consulted and eligible patients. Through the pre- and postintervention phases, family members of consulted patients and CICU team members were surveyed. Results:Preintervention (January 2020 to December 2021), PPC consultation rates were 35% (n = 34) and increased to 63% (n = 43) postintervention (January 2022 to February 2023) (P < 0.01). The timing of consultation was similar between phases. Survey results from family members (n = 19, 39% of 49 participants) and CICU team members (n = 80, 40% of eligible) revealed predominantly positive perceptions regarding PPC involvement. Conclusions:QI interventions, including collaborative huddles and digital prompts based on discrete screening criteria, lead to significantly increased rates of PPC consultation in patients with heart disease in the CICU. Survey results support PPC consultation as a positive contribution for families and CICU team members.

Background Trastuzumab and multiagent chemotherapy have been the standard of care for the 20-30% of metastatic gastric and esophageal adenocarcinomas that overexpress HER2. Preclinical data show that trastuzumab requires a functional adaptive immune system for efficacy, suggesting synergy of trastuzumab combined with immune checkpoint inhibitors, further supported by current clinical studies. Methods HCRN GI17-319 was a multicenter, single-arm, phase II clinical trial with a prespecified 6-subject safety run-in of the anti-PD-L1 antibody avelumab, combined with trastuzumab and mFOLFOX6, in previously untreated, metastatic, HER2-amplified gastric and esophageal adenocarcinomas. The primary endpoint was the best overall response within 24 weeks. Subjects received 9 cycles of induction avelumab, trastuzumab, and mFOLFOX6, followed by maintenance avelumab + trastuzumab. The study was initially designed as a Simon’s 2-stage trial, but enrollment was stopped after the 18-subject first stage for reasons unrelated to safety or efficacy. Results A total of 18 subjects, including the 6-subject safety run-in, were enrolled 4/2019-8/2020. The 24-week response rate was 11/18 (61%; 95% CI: 39%-84%), and the confirmed overall response rate is 9/18 (50%). With a median follow-up of 14.6 months, the median PFS was 8.0 months (95% CI: 5.3-NA) and median OS was 13.1 months (95% CI: 11.5-NA). The regimen was well tolerated, without any new safety signals. Conclusions The combination of avelumab, trastuzumab, and FOLFOX chemotherapy demonstrated some activity, with a reasonable response rate and median PFS. These outcomes provide some support to other clinical trials of similar agents and support the future evaluation of adding avelumab in this setting. NCT03783936.

BACKGROUND:Standard therapy for patients with KRAS/NRAS/BRAF wild-type (WT), microsatellite stable (MSS), L-sided metastatic colorectal cancer (mCRC) often includes chemotherapy with a monoclonal antibody (mAb) that targets epidermal growth factor receptor (EGFR) such as cetuximab. Preclinical studies suggest the role of CDK4/6 activity downstream of EGFR as a possible resistance mechanism to anti-EGFR therapy. Therefore, we hypothesized that the addition of the CDK4/6 inhibitor palbociclib would increase the disease control rate of patients with anti-EGFR naïve KRAS/NRAS/BRAF-WT mCRC. METHODS:LCCC1717 was a phase II trial with a Simon two-stage design in which patients with KRAS/NRAS WT mCRC having progressed on at least two lines of therapy were given palbociclib and cetuximab. The primary end point was four-month disease control rate (DCR). Secondary endpoints were overall survival (OS) and progression-free survival (PFS). If six or more patients achieved disease control at four months, the study would continue enrollment, otherwise the study would be discontinued. RESULTS:A total of 12 subjects were enrolled, 11 of whom had left-sided colon cancer. The four-month DCR was 41.7% (95% CI 15% to 72%) with median OS at 13.9 months and median PFS of 5.3 months, which did not meet the pre-specified endpoint of efficacy. The treatment combination was well tolerated with the most common treatment-related toxicity being decreased lymphocyte and neutrophil counts. CONCLUSION:While clinical benefit was observed with the combination, it did not meet its pre-specified endpoint for efficacy in patients with KRAS/NRAS/BRAF WT EGFR therapy-naïve mCRC patients. Clinicaltrials.gov Identifier: NCT03446157.

CONTEXT:Pediatric hospice provides care for children during the final stages of a terminal illness, usually defined as a prognosis of six months or less. There is limited data to inform hospice utilization in children among different hospice diagnoses. OBJECTIVE:The objective of this study is to perform a retrospective analysis of pediatric hospice patients to better describe clinical trends and utilization among different hospice diagnoses. METHODS:This is a single center retrospective study of pediatric hospice patients enrolled in hospice from 2015-2023 (0-23 y). Using descriptive statistics, the study examines hospice diagnoses, hospice length of stay (LOS), and the type of hospice care, traditional or concurrent care hospice. RESULTS:One hundred fifty-five pediatric hospice patients met criteria. Children were divided into the four most common diagnostic categories: oncologic (n = 54), neurologic (n = 41), genetic/metabolic (n = 38), and cardiovascular (n = 22). Children who received concurrent care hospice had significantly longer median hospice LOS compared to traditional hospice care (33d vs. 14d; P < 0.001). More than half of the children spent less than one month in hospice (90/155, 58%) with 20% having a late referral defined as hospice LOS ≤ 3 days. There were no statistically significant results between LOS in the four most common diagnostic categories. CONCLUSION:Hospice LOS was not statistically different across diagnostic categories. Children enrolled in concurrent care hospice have statistically significant longer stays in hospice compared to traditional hospice. Short hospice stays and late referrals continue to occur.

The influence of ethnicity and language preference on palliative and end-of-life (EOL) experiences in children with cancer is poorly understood. Existing data relies on adult studies and suggests that patients from underserved populations often receive inferior palliative and EOL care, characterized by medically intense care at EOL. This qualitative study explores the EOL experiences of English and Spanish-preferring families of children with poor-prognosis cancers, with the hypothesis that language-based disparities exist. English and Spanish-preferring parents of children with poor-prognosis cancers, and bereaved parents whose children died of cancer within the last 5 years were eligible. Language preference and ethnicity data were obtained from the patient chart and confirmed by self-report during interviews. We conducted 11 interviews with 15 caregivers: 6 in Spanish and 5 in English. Interviews were recorded, transcribed, and analyzed using Braun and Clarke inductive coding approach. Our analysis revealed that many Hispanic, particularly Spanish-preferring families, reported disparities compared with non-Hispanic families, including inconsistent interpreter use, confusion about prognosis and treatment, perceived discrimination, inadequate EOL anticipatory guidance, and dissatisfaction with hospice. The study identifies perceived gaps in our current practices that negatively impact pediatric Hispanic, Spanish-preferring patients and their families. Larger scale studies are needed to further explore the influence of language preference on EOL experiences. There is a critical need to better assess the effective delivery of pediatric palliative care among Spanish-preferring families, and interventions to reduce disparities in EOL/palliative care should be founded on the expressed needs of families who prefer to communicate in languages other than English.

PURPOSE Panitumumab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR), is standard therapy for patients with KRAS/NRAS/BRAF wild-type (WT), microsatellite stable (MSS), metastatic colorectal cancer (mCRC). We hypothesized that the addition of ipilimumab (anti–cytotoxic T-cell lymphocyte-4) and nivolumab (anti-PD1) to panitumumab would increase response rate. METHODS This is a phase II, multicenter, single-arm trial of panitumumab, ipilimumab, and nivolumab in KRAS / NRAS / BRAF WT, MSS mCRC. Eligible patients had received ≥1 previous lines of therapy and no previous anti-EGFR or immune checkpoint inhibitor. Patients received ipilimumab 1 mg/kg IV once every 6 weeks, nivolumab 240 mg IV once every 2 weeks, and panitumumab 6 mg/kg IV once every 2 weeks until progression, toxicity, or patient withdrawal. The primary outcome was overall response rate at 12 weeks. Using a Simon's two-stage design, with null and alternative hypothesis response rates of 22% and 35%, responses in ≥17 patients of 56 would be considered worthy of additional study. RESULTS In 56 patients enrolled between March 2018 and June 2020, the response rate was 32.1% (95% CI, 21.4 to 45.2; n = 18). The median progression-free survival was 6.0 months (95% CI, 5.5 to 7.4), and the median overall survival was 17.4 months (95% CI, 14.2 to 27.5). With a median follow-up of 43.3 months (95% CI, 41 to 55), four patients (10.7%) were alive without progression, including two patients with liver metastases. There was one treatment-related grade 5 myocarditis. The most common treatment-related grade 3 to 4 toxicities included lipase increased (9%), amylase increased (7%), ALT increased (5%), AST increased (5%), diarrhea (5%), hypophosphatemia (5%), and maculopapular rash (5%). CONCLUSION The combination of panitumumab, ipilimumab, and nivolumab demonstrated an acceptable response rate including a signal of durable response even among patients with liver metastases, suggesting activity of immune checkpoint inhibitors combined with anti-EGFR therapy in MSS mCRC.

PI3K/AKT pathway activation may confer chemotherapy resistance, so combining PI3K-targeted therapy with oral chemotherapy is appealing but can have additive toxicity. This phase I study of alpelisib, an oral alpha-specific class I PI3K inhibitor, combined with capecitabine in patients with HER2-negative metastatic breast cancer found that the combination was safe, tolerable, and demonstrated clinical benefit. Background: Alpelisib is an oral alpha-specific class I PI3K inhibitor approved in combination with fulvestrant for the treatment of PIK3CA -mutated hormone receptor-positive (HR + ), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. The tolerability of this drug with the oral chemotherapy capecitabine is unknown. Patients and Methods: This phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of alpelisib (250 mg or 300 mg daily for 3-weeks) with capecitabine (1000 mg/m2 twice daily for 2-weeks followed by a 1-week rest period) in patients with metastatic HER2-negative breast cancer, regardless of PIK3CA mutation status. Results: Eighteen patients were treated with alpelisib-capecitabine. Half of the patients had HR + breast cancer, and 16 had prior systemic therapy for metastatic disease. The MTD of alpelisib was 250 mg daily in combination with capecitabine 1000 mg/m2 twice daily. DLTs included hyperglycemia, QTc prolongation, fatigue, and chest pain. The most common grade 3 adverse event (AE) was hyperglycemia (28%). No grade 4 AEs were observed. Three patients discontinued therapy due to an AE. One-third of patients required dose reduction of both alpelisib and capecitabine. Four patients experienced a partial response and 8 patients experienced stable disease. The median progression-free survival was 9.7 months (95% CI 2.8-13.5 months) and median overall survival was 18.2 months (95% CI 7.2-35.2 months). Twelve patients had PIK3CA mutation testing completed, of these 2 had known or likely deleterious PIK3CA mutation. Conclusion: This study provides safety data for an oral combination therapy of alpelisib-capecitabine and defines tolerable doses for further study.

Background: Chimeric antigen receptor T cells targeting CD30 (CD30.CAR) are safe and with promising efficacy when preceded by lymphodepleting chemotherapy. Methods: In a phase 1 dose-escalation study, we assessed the safety of CD30.CAR-T cell infusion as consolidation after carmustine, etoposide, cytarabine, and melphalan (BEAM) autologous stem cell transplant (ASCT) in adult and pediatric patients with high risk relapsed/refractory classical Hodgkin lymphoma (HL) and CD30+ non-Hodgkin lymphoma (NHL). Patients received autologous CD30.CAR-T cells after trilineage hematopoietic engraftment defined as absolute neutrophil count ≥500/mm3 for 3 days, platelets ≥25x109/L and hemoglobin ≥ 8 g/dL without transfusion for 5 days. Findings:T wenty-one patients were enrolled and 18 patients (11 HL, 6 T cell lymphoma, 1 grey zone lymphoma) were infused with CD30.CAR-T cells at a median of 21.5 days (range 17-44 days) after ASCT. There were no dose limiting toxicities from the CAR-T cell product. One patient had grade 1 cytokine release syndrome. At a median follow up of 48 months post infusion, the median progression free survival (PFS) for all patients is 31.5 months and the median PFS for HL patients has not been reached. The 2-year PFS for HL patients was 73%. The median overall survival for all patients has not been reached. CD30.CAR-T cell expansion and persistence in the peripheral blood were similar across CAR-T cell dose levels and comparable to that previously observed in patients post lymphodepleting chemotherapy. Interpretation: CD30.CAR-T cell infusion as consolidation after BEAM ASCT has low rates of toxicity and encouraging efficacy in HL patients at high risk of relapse. Funding: This work was supported by an NHLBI-R01HL114564 and University Cancer Research Fund at the Lineberger Comprehensive Cancer Center. NSG was supported by Lymphoma Research Foundation Career Development Award.Declaration of Interest: The University of North Carolina (UNC) has a research collaboration with Tessa Therapeutics. Competing interests of authors from UNC (GP, JSS, BS) are managed in accordance with institutional policies. This study was monitored by an independent Data Safety Monitoring Committee. NSG has served on an advisory board or consulted for Novartis, Kite, Seagen, ADC Therapeutics, and Caribou Biosciences. MLR is employed by Iqvia Biotech. WAW has done consulting for Teladoc, has been on advisory board for Koneksa Health and Quantum Health, has research funding from Pfizer and Genentech and salary support from the ASH Research Collaborative.Ethical Approval: This study was conducted in accordance with the Declaration of Helsinki and International Conference on Harmonization Guidelines for Good Clinical Practice (CT.gov #NCT02663297) and was approved by the institutional review board at UNC. All patients or parents/legal guardians provided written informed consent.

INTRODUCTION: In Cushing disease, the definition of success after resection of corticotroph adenomas remains unclear given inconsistent pathology and high recurrence rates despite initial biochemical remission. METHODS: We collected 12 years of in-hospital cortisol data after the removal of pathology-confirmed corticotroph adenomas in patients with Cushing disease. A novel cortisol halving time analysis was performed using exponential decay modeling, results were dichotomized a priori, and then applied to an external cohort of patients. Halving time was compared to first post-operative cortisol and nadir cortisol variables by estimating long-term remission and time-to-recurrence using Cox regression modeling and the Kaplan-Meier method. RESULTS: A total of 320 patients met inclusion/exclusion criteria for the final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 2.1 years, although 62 patients had five years or longer follow-up time. Higher first post-operative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first post-operative cortisol = 50 µd/dL were 4.1 times more likely to recur than those with a first post-operative cortisol < 50 µd/dL (HR 4.1, 1.8-9.2; p = 0.0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, p = 0.18). Patients with a nadir cortisol =2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, p < 0.0001). CONCLUSIONS: Post-operative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first post-operative cortisol and cortisol halving time, a nadir < 2 µg/dL occurring within the first three post-operative days showed the strongest association with long-term remission.

Outcomes1. Describe caregiver decision-making experiences regarding tracheostomy placement in infants with severe bronchopulmonary dysplasia, including from families that have chosen not to proceed with tracheostomy and families that speak Spanish.2. Practically integrate caregiver perspectives and advice to improve clinical care for other families facing this decision.Key MessageThrough this convergent mixed-methods study, we explore caregiver decision-making and advice regarding tracheostomy in infants with severe bronchopulmonary dysplasia. Caregiver perspectives reveal an educational gap in long-term lived experience with tracheostomy. Communication with other families, support from Palliative Care, and interactions with knowledgeable providers are essential to support decision-making and alleviate fears surrounding tracheostomy.Introduction/ContextBronchopulmonary dysplasia (BPD) is a chronic respiratory disease that commonly affects preterm infants due to interruptions in pulmonary development. In infants with severe BPD, families often face the decision of tracheostomy placement, which is difficult due to unclear long-term outcomes, quality of life impacts, and associated financial and emotional burden.MethodsWe developed this convergent mixed-methods study using a logic model based on an existing framework of shared decision-making for children with chronic illnesses. It is comprised of semi-structured interviews and surveys of caregivers of children with severe BPD who were offered tracheostomy. Caregivers must be English- or Spanish-speaking and >/=6 months from decision. Interview topics include resources/information, involvement of palliative care, emotional well-being, and advice. Surveys include sociodemographics, system support, decisional conflict, health literacy, and caregiver burden. Two independent coders will analyze interview transcripts using grounded theory and will conduct subgroup analyses based on survey measures.ResultsWe interviewed n=8 caregivers: median age 32 years, 86% female, 86% Caucasian, 29% Hispanic/Latino, median decisional conflict score 15. Caregivers highly valued lived experience in their decision-making process and in alleviating fears surrounding education gaps, such as tracheostomy cares and impact on quality of life. Caregivers perceived providers’ familiarity with these concepts to significantly affect their advice, and perceived Palliative Care to be a helpful support and advocate. Caregivers that postponed tracheostomy attributed this to hope for clinical improvement and fear of tracheostomy. Overall, caregivers found tracheostomy to improve quality of life and advise other parents of children with severe BPD to get a tracheostomy.ConclusionCurrent educational efforts focus on acute implications of the decision regarding tracheostomy rather than long-term lived experience. Education on this, ideally from other families, is essential to tracheostomy decision-making from caregivers’ perspectives. Palliative Care may be a team that could address this gap.KeywordsShared Decision Making / Advance Care Planning; Communication

Background Chimeric antigen receptor (CAR) T cells targeting CD30 are safe and have promising activity when preceded by lymphodepleting chemotherapy. We aimed to determine the safety of anti-CD30 CAR T cells as consolidation after autologous haematopoietic stem-cell transplantation (HSCT) in patients with CD30 + lymphoma at high risk of relapse. Methods This phase 1 dose-escalation study was performed at two sites in the USA. Patients aged 3 years and older, with classical Hodgkin lymphoma or non-Hodgkin lymphoma with CD30 + disease documented by immuno histo chemistry, and a Karnofsky performance score of more than 60% planned for autologous HSCT were eligible if they were considered high risk for relapse as defined by primary refractory disease or relapse within 12 months of initial therapy or extranodal involvement at the start of pre-transplantation salvage therapy. Patients received a single infusion of CAR T cells (2 x 10(7) CAR T cells per m(2) , 1 x 10(8) CAR T cells per m(2) , or 2 x 10(8) CAR T cells per m(2) ) as consolidation after trilineage haematopoietic engraftment (defined as absolute neutrophil count >= 500 cells per mu L for 3 days, platelet count >= 25 x 10(9) platelets per L without transfusion for 5 days, and haemoglobin >= 8 g/dL without transfusion for 5 days) following carmustine, etoposide, cytarabine, and melphalan (BEAM) and HSCT. The primary endpoint was the determination of the maximum tolerated dose, which was based on the rate of dose-limiting toxicity in patients who received CAR T-cell infusion. This study is registered with ClinicalTrials.gov (NCT02663297) and enrolment is complete. Findings Between lune 7, 2016, and Nov 30, 2020, 21 patients were enrolled and 18 patients (11 with Hodgkin lymphoma, six with T-cell lymphoma, one with grey zone lymphoma) were infused with anti-CD30 CAR T cells at a median of 22 days (range 16-44) after autologous HSCT. There were no dose-limiting toxicities observed, so the highest dose tested, 2 x 10(8) CAR T cells per m 2 , was determined to be the maximum tolerated dose. One patient had grade 1 cytokine release syndrome. The most common grade 3-4 adverse events were lymphopenia (two [11%] of 18) and leukopenia (two [11%] of 18). There were no treatment-related deaths. Two patients developed secondary malignancies approximately 2 years and 25 years following treatment (one stage 4 non-small cell lung cancer and one testicular cancer), but these were judged unrelated to treatment. At a median follow-up of 482 months (IQR 275-607) postinfusion, the median progression-free survival for all treated patients (n=18) was 323 months (95% CI 46 months to not estimable) and the median progression-free survival for treated patients with Hodgkin lymphoma (n=11) has not been reached. The median overall survival for all treated patients has not been reached. Interpretation Anti-CD30 CAR T-cell infusion as consolidation after BEAM and autologous HSCT is safe, with low rates of toxicity and encouraging preliminary activity in patients with Hodgkin lymphoma at high risk of relapse, highlighting the need for larger studies to confirm these findings.

Outcomes1. Attendees will be able to identify the methods used to abstract and characterize pain from the electronic health record of children and adolescents with cancer receiving palliative care services.2. Attendees will be able to describe the trends in pain documentation across a cohort of children and adolescents with cancer receiving palliative care services.Key MessagePediatric palliative care teams can help to address complex pain care needs of children and adolescents with cancer. Our study evaluated documentation of pain characteristics in pediatric palliative care team clinical notes. While physical characteristics were commonly documented, pain's impact on well-being and daily living were less evident.ImportanceAlthough pain reporting and treatment among children and adolescents with cancer has improved, less focus has been on capturing pain characteristics to tailor pain care strategies. Clinical documentation by pediatric palliative care teams may provide valuable insights to evaluating multifaceted pain care needs of children with cancer.Objective(s)To characterize pediatric palliative clinicians’ documentation of pain characteristics among children and adolescents with cancer.Scientific Methods UtilizedWe retrospectively evaluated electronic health records of 115 pediatric oncology patients (61 males; 6-17 years, median 13 years) who initiated palliative care services at a children's hospital in the Intermountain West between October 2017-January 2021. Our team abstracted symptom care-related statements from 661 palliative care consultation and progress notes. We used content analysis with a modified coding scheme based on standards for pain outcome measures in pediatric pain clinical trials. We achieved K ≥.90 inter-rater reliability.ResultsThe sample included 29 (25.2%) patients with Hispanic/Latino ethnicity, 13 (11.3%) who spoke a language other than English, and 56 (48.7%) who lived 35 miles or greater from the children's hospital. We coded 499 pain characteristics across 68 (59.1%) patients. The most frequently documented characteristic was location (56 patients, 165 statements), followed by severity (47 patients, 109 statements), and frequency (32 patients, 73 statements). Descriptions of pain type, physical/functional impact, and escalating factors were documented in less than 25% of patients. The influence of pain on the patient's overall well-being and social life was evident in less than 10% of patients.Conclusion(s)Pediatric palliative clinicians frequently documented physical pain characteristics for children with cancer, however evidence illustrating pain-related life impact was inconsistent.ImpactPain is a priority symptom for children and adolescents with cancer. The standards for pain outcome measures provide a useful framework for evaluating pediatric palliative care documentation and can guide future research.

Previous work from our group and others has shown that patients with breast cancer can generate a T cell response against specific human epidermal growth factor 2 (HER2) epitopes. In addition, preclinical work has shown that this T cell response can be augmented by Ag-directed mAb therapy. This study evaluated the activity and safety of a combination of dendritic cell (DC) vaccination given with mAb and cytotoxic therapy. We performed a phase I/II study using autologous DCs pulsed with two different HER2 peptides given with trastuzumab and vinorelbine to a study cohort of patients with HER2-overexpressing and a second with HER2 nonoverexpressing metastatic breast cancer. Seventeen patients with HER2-overexpressing and seven with nonoverexpressing disease were treated. Treatment was well tolerated, with one patient removed from therapy because of toxicity and no deaths. Forty-six percent of patients had stable disease after therapy, with 4% achieving a partial response and no complete responses. Immune responses were generated in the majority of patients but did not correlate with clinical response. However, in one patient, who has survived >14 y since treatment in the trial, a robust immune response was demonstrated, with 25% of her T cells specific to one of the peptides in the vaccine at the peak of her response. These data suggest that autologous DC vaccination when given with anti-HER2-directed mAb therapy and vinorelbine is safe and can induce immune responses, including significant T cell clonal expansion, in a subset of patients.