Kazmi, Syed Mohammad Ali

Abstract Background Neuroendocrine tumors (NETs) are rare, heterogeneous neoplasms associated with prolonged survival and substantial symptom burden. However, patient-reported outcomes across NET subtypes remain poorly characterized, particularly in real-world settings. This study describes baseline health-related quality of life (HRQoL) and care experiences among patients with gastroenteropancreatic and lung NETs, examining differences by tumor site and time since diagnosis. Methods The Neuroendocrine Tumors–Patient Reported Outcomes study is a prospective, multi-institutional US cohort of adults (aged 18 years and older) with incident small intestinal, pancreatic, gastroenteropancreatic, or lung NETs diagnosed from January 2018 through September 2024, identified via a validated electronic medical record–based computable phenotype. Baseline surveys assessed HRQoL, symptoms, care experiences, and clinical characteristics using validated instruments. Descriptive statistics and standardized mean differences compared responses by NET site and time since diagnosis. Results Among 2367 participants (mean age = 57.8 years; 57.3% female), 1974 had gastroenteropancreatic NETs (659 small intestinal NET, 555 pancreatic NET) and 393 had lung NETs. Fatigue (mean = 33.0), insomnia (mean = 32.5), and diarrhea (mean = 25.7) were the most burdensome symptoms. Lung NET patients reported worse dyspnea (standardized mean difference = 0.58, P < .001) and lower physical, role, and global QoL scores than those with gastroenteropancreatic NETs, while pancreatic NET patients reported better functioning. Diarrhea worsened over time, especially in small intestinal NETs. Most rated care highly (75.3%) but cited concerns about treatment side effects (80.4%), costs (60.7%), and travel burden (58.8%). Conclusions This large US cohort reveals persistent symptom burden and HRQoL variation by tumor site and disease duration, underscoring the need for longitudinal HRQoL assessment in NET care.

TPS3641 Background: Patients with mismatch repair proficient (pMMR) BRAF V600E mutant high-risk stage II (T4) or stage III colon cancer have a substantial risk of recurrence despite standard adjuvant therapy. In patients with metastatic BRAF V600E mutant colorectal cancer, the combination of the RAF inhibitor encorafenib and the EGFR inhibitor cetuximab has been shown to improve overall and progression-free survival compared to standard therapy after at least one prior line of therapy. This study will evaluate if this combination improves disease-free survival (DFS) in patients with resected BRAF V600E mutant pMMR/microsatellite stable (MSS) high-risk stage II (T4) or stage III colon cancer after standard adjuvant therapy. Methods: The study has a seamless phase II/III design, enrolling a maximum of 394 patients. BRAF mutation status can be determined locally or submitted for central testing in trial pre-screening. Eligible patients will be randomized 1:1 to usual surveillance versus 6 months of treatment with encorafenib (300mg oral daily) plus cetuximab (500mg/m2 intravenous every 14 days). Stratification factors are adjuvant chemotherapy regimen (FOLFOX versus CAPOX), duration of adjuvant therapy (3 months versus > 3 months), tumor stage (T4N0 versus T1-3N1 versus T4N1/TanyN2), and ctDNA marker status (detectable versus undetectable) at randomization. Adjuvant therapy must be completed at most 8 weeks prior to registration. For the phase II component, in the ctDNA detectable cohort, the primary endpoint will be ctDNA clearance rate at 6 months, and, in the ctDNA undetectable cohort, the primary endpoint will be 6-month ctDNA recurrence-free survival, where events consist of death, recurrence, or ctDNA positivity. The primary endpoint of the phase III component is DFS, and secondary endpoints are overall survival, adverse events, and alternative DFS calculated from the date of primary resection, rather than date of study randomization. Patient reported symptoms (PRO-CTCAE) will be collected and analyzed as an exploratory endpoint, and serial blood banking will support future correlative studies. The trial will proceed to the phase III portion if either of the two endpoints in the phase II cohorts is statistically superior in patients receiving encorafenib plus cetuximab. The phase III study sample size will provide 80% power at a one-sided α of 0.05 to detect an approximately 10% improvement in the three-year DFS rate, assuming 68% in the control arm. Two interim analyses will be performed for DFS endpoint. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org . U10CA180820 (ECOG-ACRIN); U10CA180868 (NRG); U10CA180888 (SWOG); Pfizer, Eli Lilly; Clinicaltrials.gov ID: NCT05710406. Clinical trial information: NCT05710406 .