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4235 Background: Malignant portal vein tumor thrombus (PVTT) arising from hepatic metastases is associated with poor prognosis, rapid hepatic decompensation, and limited effective local treatment options despite systemic therapy. In real-world practice, local treatment intensity is frequently adapted to disease burden and treatment response. We evaluated outcomes of a risk-adapted, step-up local treatment strategy using microwave ablation (MWA) alone or in combination with iodine-125 (I-125) seed implantation for patients with malignant PVTT. Methods: We retrospectively reviewed patients with hepatic metastases treated with MWA with or without I-125 seed implantation between 2023 and July 2025. In clinical practice, MWA alone was preferentially used for patients with relatively limited disease burden, while MWA plus I-125 was employed as an escalation strategy for patients with more advanced PVTT or disease progression following MWA alone. The primary endpoint was PVTT-directed local outcome, defined as portal vein patency and/or local control of tumor thrombus on follow-up imaging. Secondary endpoints included progression-free survival (PFS), overall survival (OS), hepatic function changes, and treatment-related toxicity. Survival analyses were considered exploratory. Results: A total of 73 patients were included, of whom 50 were treated with MWA alone and 23 with MWA plus I-125 seed implantation. Patients receiving MWA plus I-125 demonstrated more advanced disease characteristics, including universal presence of PVTT and higher disease stage, consistent with treatment escalation by disease severity. Among patients with PVTT, MWA plus I-125 achieved portal vein patency and/or local control in 65% at first follow-up imaging. Treatment-related toxicities were manageable, with no unexpected grade ≥3 adverse events attributable to I-125 implantation. Median PFS was 11.5 months in patients treated with MWA alone and 9.9 months in patients treated with MWA plus I-125, consistent with greater baseline disease burden in the latter group. Conclusions: MWA alone and MWA plus I-125 function as complementary components of a risk-adapted, step-up local treatment strategy for malignant PVTT from hepatic metastases. Escalation to MWA plus I-125 appears feasible in patients with advanced or refractory PVTT and demonstrates a potential signal for improved PVTT-directed local control and portal vein patency. Prospective studies focused on PVTT-specific endpoints are warranted.

4514 Background: Maintenance avelumab is a standard of care in patients (pts) with la/mUC who do not progress after first-line PBC. Cabozantinib (CABO) is an oral inhibitor of MET, VEGFR and TAM, active in multiple solid tumors. We hypothesized that an avelumab (Av)-CABO combination would improve outcomes in pts with mUC with an acceptable safety profile compared to avelumab maintenance alone. Methods: MAIN-CAV (NCT05092958) is a phase III randomized, multicenter, international trial for la/mUC pts who did not progress after 4-6 cycles of any PBC (gemcitabine-cisplatin, gemcitabine-carboplatin, MVAC, ddMVAC). Pts were randomized 1:1 to Av 800 mg IV every 2 weeks alone or with CABO 40 mg daily for ≤2 years. Stratification factors were response to first-line PBC (complete response [CR] vs partial response [PR] vs stable disease [SD]) and visceral metastases. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), safety and quality of life. The target accrual was 654 pts; the trial closed early after enrollment of 68 pts following adoption of enfortumab vedotin plus pembrolizumab as the new preferred first-line standard in the US. Results: From 3/2022 to 3/2024, 68 pts were randomized (Av n = 33; CABO-Av n = 35). Median OS was 24.8 months (mo) with Av and 23.0 mo with Avb-CABO (Hazard ratio 1.41; 95% CI 0.66–3.01; p = 0.186). Median PFS was 4.6 mo with Av vs 6.0 mo with Av-CABO (p = 0.343). Objective response rate among pts with PR or SD after first-line PBC was 20.8% with Av vs 11.5% with Av-CABO (p = 0.424). Grade ≥3 treatment-related adverse events occurred in 24.2% pts on the Av arm vs 39.4% of pts on the Av-CABO arm and CABO dose reductions occurred in 63% of pts. Conclusions: Addition of CABO to Av did not improve OS or PFS compared with Av alone in this underpowered, prematurely closed phase III trial; safety was consistent with known profiles. U10CA180821,U10CA180882; U24CA196171, U10CA180863. (CCTG);U10CA180888 (SWOG); https://acknowledgments.alliancefound.org. Clinical trial information: NCT05092958 .

4565 Background: EVP is the preferred 1 st -line regimen for patients (pts) with aUC. EV-related toxicities are often managed with dose adjustments, such as reductions and holds. Analysis of EV monotherapy trials showed consistent survival outcomes despite dose adjustments. We hypothesized that on-treatment EV dose adjustments would not impact survival in these pts. Methods: Pts with aUC treated with EVP in the multisite UNITE study were analyzed. Early dose reductions (DR) and holds were defined as occurring < 9 weeks from EVP start, with the remainder classified as late. Pts with DR at treatment start were excluded. Survival endpoints were progression-free survival (PFS) and overall survival (OS) from EVP start, assessed by Kaplan-Meier analysis and Cox models. Multivariable Cox analysis (MVA) included age (≥ 75 vs < 75), ECOG performance status (0-1 vs 2-3), Hgb level (< 10 vs ≥ 10) and liver metastases (present vs not). A time-dependent covariate was used to reduce immortal time bias. Complementary MVA landmark analyses were performed, aligned to the total number of treatment cycles received, with six analyses from cycles 2 to 7. Results: 360 pts from 17 sites were included (median age 70; 78% Caucasian; 76% male; 27% upper tract primary; 35% histology subtype component; 17% with liver metastasis; 78% frontline); median follow-up was 11.7 months (95% CI [10.79, 13.08]). Median number of cycles was 6 in pts with DR and 3 with no DR. Early DRs (100 pts [28%]) and holds (18 pts [5%]) were most commonly due to rash (28% of all early DRs and holds). Late DR (75 pts [21%]) and holds (50 pts [14%]) were most commonly due to neuropathy (52% of all late DRs and holds). Pts with early or late DR had longer PFS and OS vs those who did not (Table); however, there was no significant PFS or OS difference with dose hold vs no hold (PFS HR 0.65, 95%CI (0.40, 1.05), p = 0.08; OS HR 0.70, 95%CI (0.39, 1.27), p=0.24). In landmark analyses, about 50% of pts had DR; no significant difference in PFS or OS was observed at most landmarks, except for longer OS in the DR cohort at cycle 4 (HR 0.53, 95% CI (0.29, 0.98), p = 0.042) and cycle 5 (HR 0.43, 95% CI (0.19, 0.99), p = 0.048). Conclusions: In this real-world retrospective analysis, EVP efficacy was maintained despite DR and dose holds. Survival difference noted in the time-dependent analyses were not consistently reproduced in landmark analyses, suggesting exposure-related selection bias rather than causal effect. Prospective studies are warranted to validate these hypothesis-generating findings. Association of EV DR with PFS/OS (time-dependent analyses). Early DR Late DR DR vs no DR outcomes UVAHR (95% CI), p MVAHR (95% CI), p UVAHR (95% CI), p MVAHR (95% CI), p PFS 0.50 (0.35, 0.72), <.001 0.56 (0.38, 0.84), 0.005 0.32 (0.21, 0.49), <.001 0.36 (0.23, 0.57), <.001 OS 0.51 (0.32, 0.79), 0.003 0.57 (0.35, 0.92), 0.022 0.26 (0.15, 0.45), <.001 0.31 (0.17, 0.55), <.001

4562 Background: Approximately 50-80% of patients (pts) with la/mUC have tumors with HER2 protein expression. As HER2-directed therapies enter development, a robust understanding of HER2 prevalence and real-world outcomes with standard-of-care (SOC) therapies across HER2 expression subgroups is needed. SGNDV-003 (NCT05902494) is a global retrospective chart review study in which HER2 status was assessed via central lab testing and outcomes were analyzed by HER2 status in pts with la/mUC. Methods: SGNDV-003, conducted 6/2023-7/2025, included pts with la/mUC who received ≥1 prior treatment (tx) (incl. 1 line of platinum-based chemotherapy [chemo]). HER2 status was centrally tested using a UC-specific investigational immunohistochemistry [IHC] and in situ hybridization (ISH) assays. HER2 status was defined as: HER2-positive (IHC3+ or IHC2+/ISH+), HER2-low (IHC2+/ISH- or IHC1+), HER2-expressing (IHC3+, 2+, 1+), and HER2-zero (IHC0). Index line of therapy (LOT) was defined as the first LOT received after platinum-based chemo. Outcomes included real-world objective response rate (rwORR) (per RECIST 1.1 or physician-assessed response) to index LOT, real-world progression-free survival (rwPFS), and overall survival (OS) from start of index LOT. Data was analyzed via descriptive statistics. Results: A total of 353 pts with la/mUC and available HER2 status were analyzed (male, 76%; median age, 70 years). 70% of pts were HER2 expressing (19% HER2-positive, 51% HER2-low); 30% were HER2-zero. Disease characteristics were well balanced by HER2 status. Index LOT tx and real-world outcomes are shown in the Table. Immuno-oncology therapies (IO) and enfortumab vedotin (EV) were the most common index LOTs. For IO, rwORRs were 21% for HER2-expressing and 17% for HER2-zero. For EV mono, rwORRs were 36% (HER2-expressing) and 38% (HER2-zero), respectively. Conclusions: This global study provides a robust estimate of HER2 distribution in la/mUC based on standardized central lab testing, showing high prevalence of HER2 expression. Real-world outcomes with current SOC therapies were broadly consistent across HER2 subgroups, establishing an important benchmark for the clinical development of HER2-directed therapies in this setting. HER2-positive (n=67) HER2-low (n=181) HER2-expressing (n=248) HER2-zero (n=105) Total (n=353) Real-world Outcomes rwORR, n (%)[95% CI] 17 (25.4)[15.5, 37.5] 50 (27.6)[21.3, 34.7] 67 (27.0)[21.6, 33.0] 22 (21.0)[13.6, 30.0] 89 (25.2)[20.8, 30.1] Median rwPFS (95% CI), mo 2.8(2.0, 4.1) 3.7(2.7, 5.1) 3.0(2.7, 4.5) 2.6(2.1, 3.4) 2.9 (2.6, 3.5) Median OS(95% CI), mo 12.2(9.3, 16.5) 11.5(9.5, 13.5) 11.9(10.3, 13.4) 7.7(5.9, 9.9) 10.8(9.1, 12.3) Index LOT, n% IO EV monoChemoOther tx 37 (55)17 (25)10 (15)3 (5) 94 (52)51 (28)24 (13)14 (8) 131 (53)68 (27)34 (14)17 (7) 65 (62)21 (20)12 (11)7 (7) 196 (56)89 (25)46 (13)24 (7)

4515 Background: Adenocarcinomas of the urinary tract are rare malignancies with limited prospective data. Outcomes of triplet chemotherapy remain poorly defined. Methods: This was a prospective, single-arm, phase II study (NCT00082706) conducted at MD Anderson. Between 2005 and 2010, patients (pts) aged ≥18 years with ECOG 0–2 and metastatic or unresectable urachal (UA) or non-urachal adenocarcinoma (NUA) received frontline GemFLP (5-fluorouracil 200 mg/m² continuous infusion ×5 days with leucovorin 23 mg IV daily ×5; cisplatin 20 mg/m² IV daily ×5; gemcitabine 200 mg/m² IV on days 1 and 5). Best overall response (BOR) was assessed by imaging. Primary endpoints were objective response rate (ORR) and overall survival (OS); secondary endpoint was toxicity. PFS was calculated from treatment initiation and duration of response (DoR) from first CR/PR to progression or death; time-to-event endpoints were estimated by Kaplan–Meier (KM). Post hoc analyses evaluated baseline tumor markers (CEA, CA19-9, CA125, β-hCG) Treatment-related adverse events (TRAEs) were graded per CTCAE v5. Results: Forty-six pts were enrolled (28 UA, 18 NUA). Median age was 58 years; 41% were de novo metastatic, and 78% had visceral metastases. ORR was 44% (20/46). Among responders, median DoR was 8.6 months (95% CI 4.6–30.8). median PFS was 3.3 months (95% CI 2.3–8.4) and median OS (mOS) was 21.0 months (95% CI 15.9–35.3) There was no difference in PFS (p=0.39) or OS (p=0.99) between UA and NUA. Baseline CEA, CA19-9, CA125, and β-hCG were not associated with ORR or PFS. Higher baseline CA125 was associated with inferior OS (HR 1.33, 95% CI: 1.12–1.58; p =0.001) Subsequent systemic therapy was administered to 28 pts (60.9%); median number of subsequent treatment lines was 2 (range 1–5). The most common hematologic TRAEs were anemia (28.1%; grade ≥3 [G3] 12.5%), thrombocytopenia (21.9%; G3 12.5%), and neutropenia (12.5%; G3 9.4%). The most frequent non-hematologic TRAEs were dehydration (21.9%; G3: 6.2%), diarrhea (9.4%; G3 6.2%) and catheter-related thrombosis (9.4%; G3 9.4%). No grade 5 events occurred. Conclusions: In this prospective phase II study, frontline GemFLP achieved a 44% ORR with durable responses (mDoR 8.6 mo) and 21 mo mOS in advanced UA and NUA. Survival did not differ between UA and NUA subtypes. Baseline CA125 was associated with OS. Toxicity was manageable. These data provide a prospective benchmark for this rare disease. Clinical trial information: NCT00082706 . Variable UA (n=28) NUA (n=18) Characteristics Age, median [ICR] 58 [54– 62] 58 [54– 62] 67 [ 62-72] Race, n (%) White 22 (79) 11 61) Black 6 (21) 6 (33) Other 0 1 (6) Prior surgery for localized disease, n (%) 18 (64) 5 (28) Mets at baseline Any 24 (86) 7 (39) Lung 6 (21) 4 (22) Liver 3 (11) 0 Peritoneum 17 (61) 0 Bone 3 (11) 3 (17) Nodal-only mets 1 (3) 2 (10) Outcomes ORR (%) 43.5 35.7 55.6 BOR n (%) CR 4 (14) 2 (11) PR 6 (21) 8 (44) SD 11 (39) 4 (22) PD 6 (21) 3 (17) NE 1 (4) 1 (6)

4513 Background: The AMBASSADOR trial (NCT03244381) showed that in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery, adjuvant pembrolizumab for one year improved disease-free survival from 14.2 to 29.6 months (Apolo et al, NEJM 2024). Here we report the HRQOL results. Methods: HRQOL was completed by 560 randomized patients and included the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 plus the bladder cancer supplement BLM30, and the EQ-5D-5L, which assesses overall quality of life or health state. Published minimally important difference thresholds for EQ-5D-5L is 0.06, and for EORTC instruments is 5-10 points. For all reported HRQOL data, higher score is better except BLM30 urinary symptoms, where higher score indicates more symptoms. Results: Mean changes from baseline to 12 months (corresponding to end of treatment) for each HRQOL measure are summarized in the Table. No statistically significant difference was seen between the observation vs. pembrolizumab arms. Further, numerical differences between arms for these HRQOL measures do not meet (are lower than) the published minimally clinically important difference thresholds. Conclusions: Adjuvant pembrolizumab after radical surgery for patients with high-risk muscle-invasive urothelial carcinoma improved disease-free survival without negatively affecting HRQOL. These HRQOL results add further support to adjuvant immune checkpoint blockade therapy in these patients. Support: U10CA180821, U10CA180882, UG1CA189823 (https://acknowledgments.alliancefound.org). Clinical trial information: NCT03244381 . HRQOL mean change from baseline to 12 months and between-arm comparisons. A) Observation B) Pembrolizumab Difference A vs B P-value EQ-5D-5L Index Value -.029 -.012 -.02 .45 QLQ-C30 Global Health 0.07 1.45 -1.38 .55 QLQ-C30 Physical Functioning -.089 -.069 -0.02 .99 QLQ-C30 Role Functioning 3.22 -1.23 4.45 .15 BLM30 Urinary Symptoms -3.44 -3.02 -.42 .87 BLM30 Sexual Functioning -.53 4.15 -4.68 .07

4559 Background: Baseline QOL has been linked to survival in mRCC therapy clinical trials (Cella, 2024); however, there is a paucity of prospectively collected real-world QOL data across front-line management strategies. We used data from ODYSSEY to examine the relationship between baseline QOL and early death. Methods: ODYSSEY is a multi-site, prospective observational study of 468 US pts with mRCC. Pts must have mRCC (any histology); have no prior systemic therapy (ST) or be within 3 months of starting ST; and follow up at a PCORnet study site. Exclusion criteria include treatment for cancer except mRCC. The primary objective is to determine patterns of change in QOL and symptom burden of pts with mRCC. Early death was defined as death within 12 months post-enrollment. All pts with non-missing FKSI-19 or FKSI-DRS at enrollment were included. Cumulative event probabilities as a function of time were stratified by either < or ≥ median QoL value and plotted as a step function vs time since enrollment to create cumulative event curves. To determine association between QoL at enrollment and early death, separate Cox proportional hazards models (unadjusted and adjusted) for time-to-first-event as a function of baseline QoL were fit. The adjusted model controlled for the following baseline covariates: IMDC risk (favorable vs intermediate or poor), histology (clear cell vs non). Results: As of 1/5/26, 468 pts were enrolled; 425 had non-missing FKSI-19 or FKSI-DRS at enrollment (329 immediate ST, 96 deferred ST [DST]). ST included 129 IO-IO, 108 IO-TKI, 92 Other. DST included 57 Active Surveillance, 22 Local Therapy Planned, 17 Other/Missing. 209 and 190 pts have < median FKSI-19 (score = 59) and FKSI-DRS (score = 29), respectively; 216 and 235 pts have ≥ median FKSI-19 and FKSI-DRS, respectively. Those below the median have lower rates of nephrectomy, worse IMDC risk and KPS, shorter time since RCC diagnosis, and higher rates of bone metastasis (all p<0.05). Cumulative event probabilities for death at 12 months are 21% and 7% in those < and ≥ median baseline FKSI-19, respectively; and 21% and 7% in those < and ≥ median baseline FKSI-DRS, respectively. For FKSI-19, the unadjusted hazard ratio (HR) for early death is 0.55 (95% CI: 0.43 – 0.70; p<0.001) and adjusted HR is 0.65 (0.49 – 0.85; p = 0.002) per 1 SD higher score. For FKSI-DRS, the unadjusted HR for early death is 0.57 (95% CI: 0.46 – 0.71; p<0.001) and adjusted HR is 0.66 (0.51 – 0.86; p =0.002) per 1 SD higher score (higher score indicates better QOL). Conclusions: Across management strategies in our ODYSSEY cohort of systemic therapy naïve mRCC patients, better baseline QOL was associated with better survival. This is to our knowledge the largest reported real world mRCC cohort with prospectively collected PROs. Future analyses will focus on association of outcomes with longitudinal PROs. Clinical trial information: NCT04919122 .

4183 Background: High grade neuroendocrine neoplasms (HG-NENs) are treated with platinum doublets mirroring guidelines for small cell lung cancer (SCLC) but recurrences are common and salvage options are limited in efficacy. Cabozantinib (CABO), an inhibitor of VEGFR, MET, and TAM kinases (TYRO3, AXL, and MER) was approved by the FDA for treatment of well differentiated (WD) NENs of both pancreatic and extrapancreatic origins based on the CABINET study (Chan, NEJM 2025). However, its efficacy in the whole spectrum of HG-NEN patients including poorly differentiated disease (PDD) has not been prospectively explored. Methods: This was a single institution, Phase II study of CABO in patients with HG-NENs who had progressed on at least one prior treatment. Key inclusion/exclusion criteria were NENs of any origin except SCLC, high grade by Ki-67 of > 20% or histology consensus, ECOG of < = 1, appropriate hematological parameters and no history of bleeding or active cardiac disease. CABO was given orally starting at 60 mg po daily in 3-week cycles. The primary endpoint of this study was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). A Simon optimal 2-stage design tested the null hypothesis that the true ORR is < = 1% at the type I error rate of 5%, resulting in projected enrollment of up to 32 total patients. Toxicities were graded according to CTCAE v5.0 and response was evaluated according to RECIST v1. Results: All patients have been accrued, with 4/32 patients still on treatment. Median age at diagnosis was 62 years and male to female ratio was 1.46. Origin of tumor was GI in 68.8% of the cases, the rest being thoracic (6.3%), prostate (6.3%) cervical (6.3%) head/neck (3.1%) and unknown (9.4%). Median Ki-67 was 55%, 11 patients had Ki-67 > 70%. Histology was WD-HG in 40% of patients and PDD in 60%. Two patients had mixed PDD/other components (MiNEN). Median PFS in evaluable patients was 4.01 months [95% CI 1.61 to 9.30] and mOS was 9.89 mo [95% CI 6.73 to 18.96]. Three patients so far (9.3%) have had partial response as best response (PDD-colon, WD-pancreas and PDD-cervical) while 19/32 (59.4%) patients have had stable disease as best response so far (disease control rate 68.8%). Five (15.6%) patients have received more than 10 treatment cycles. The three longest treated patients had WD-pancreas (23 and 17 cycles) and PDD-unknown (12 cycles). One patient had eventual resection of a metastatic site and is currently without evidence of disease. Three patients withdrew from the trial because of toxicities (shortness of breath, GI bleeding, thromboembolism). Twenty-six patients have expired. Conclusions: CABO monotherapy showed efficacy in some HG-NEN patients with not just WD but also the very aggressive PDD histology. No new side effects to the ones previously described for this agent were noted. Supported by Exelixis and a Siteman investment program grant. Clinical trial information: NCT04412629 .

4219 Background: Pancreatic ductal adenocarcinoma (PDAC) remains a notoriously difficult-to-treat malignancy, with limited therapy options for patients with advanced disease. While KRAS mutations are the dominant oncogenic driver in PDAC, next-generation sequencing has enabled the identification of rare, targetable alterations such as the BRAF V600E mutation, which occurs in approximately 2-3% of cases. BRAF mutant cell lines are responsive to MEK and RAF inhibitors. This study evaluates the efficacy of the combination of encorafenib and binimetinib as ≥ 2nd line therapy in this specific molecular subgroup of pancreatic cancer patients. Methods: This study used a planned two-stage design. Seven patients were pre-registered; one did not meet eligibility criteria and was excluded. Six patients were enrolled in Stage 1, which required an objective response (OR) in 40% of patients to proceed to Stage 2. Stage 2 was planned to enroll an additional 16 patients, contingent on meeting this efficacy threshold. Enrolled patients received treatment in 28-day cycles until disease progression or for a maximum of 36 cycles. Patients self-administered encorafenib (450 mg orally once daily) and binimetinib (45 mg orally twice daily) starting on Day 1 of each cycle. Objective responses were assessed using RECIST version 1.1 over 24 weeks. Results: The median number of cycles was 8. The objective response rate at 24 weeks was 33.33%. The overall objective response rate was 50%. The median time to response for progression-free survival, overall survival, duration of response, and time to response was 7.1, 15.0, 9.9, and 3.9 months respectively, with 95% CI in all categories. 50% of patients experienced at least one Grade ≥3 adverse event, including anemia, thromboembolic events, and acute kidney injury. Conclusions: The six BRAF-V600E-mutated PDAC patients in our cohort demonstrated meaningful antitumor activity with a manageable safety profile after treatment with encorafenib and binimetinib. Although the study was prematurely terminated due to limited accrual, observed objective responses and survival outcomes suggest that dual RAF/MEK inhibition may represent a feasible therapeutic strategy in this rare molecular subgroup. Larger studies are warranted to further define the efficacy and safety of this treatment combination in BRAF-V600E-mutated pancreatic cancer. Clinical trial information: NCI-2020-02972 .

4178 Background: In the CABINET trial, CABO significantly prolonged progression-free survival (PFS) compared to placebo (PB) in patients (pts) with advanced, previously treated extrapancreatic NET (epNET) or pancreatic NET (pNET) (Chan et al., NEJM, 2025). Here we report outcomes according to functional status based on NET hormone secretion. Methods: Pts with locally advanced or metastatic epNET or pNET were randomized 2:1 in separate cohorts to receive CABO 60 mg daily vs PB. Eligibility included progression by RECIST within 12 months (mo) before registration, ≥ 1 prior systemic therapy not including somatostatin analogs (SSA). Pts with functional NET due to hormone secretion and non-functional NET were included. In this post hoc subgroup analysis, we analyzed PFS by blinded independent central review and adverse events for pts receiving CABO vs PB based on functional status. Cox regression models were used with stratification on primary tumor site (epNET vs pNET). Subset analyses to evaluate treatment arm differences were conducted in pts with functional and non-functional tumors. Due to small numbers, separate results for those with unknown functional status are not included. Results: Of the total 298 pts enrolled in both cohorts, 74 had a functional NET (CABO, n = 47; PB, n = 27); 179 had a non-functional NET (CABO, n = 123; PB, n = 56); 45 had unknown functional status (CABO, n = 28; PB, n = 17). For functional NET, primary tumor sites were GI tract (n = 50; 68%), pancreas (n = 15; 20%), unknown (n = 4; 5%), lung (n = 3; 4%), and thymus (n = 2; 3%). Secreted hormones that were reported included serotonin (55%), somatostatin (18%), gastrin (16%), glucagon (4%), insulin (4%), ACTH (1%), and vasoactive intestinal peptide (1%). For non-functional NET, primary tumor sites were pancreas (n = 75; 42%), GI tract (n = 42; 23%), lung (n = 30; 17%), unknown (n = 17; 9%), thymus (n = 8; 4%), and other (n = 7; 4%). Concurrent SSA was received by 91% and 53% of pts with functional and non-functional NET, respectively. In both subgroups, CABO was associated with improved PFS compared to PB (for functional NET: stratified hazard ratio [sHR], 0.40; 95% confidence interval [CI]: 0.20-0.82, P = 0.012; for non-functional NET: sHR, 0.26; 95% CI: 0.17-0.41, P < 0.001). The most frequent grade 3/4 adverse events (AEs) attributed to CABO vs PB in pts with functional NET included hypertension (21% vs 11%), diarrhea (9% vs 11%), and fatigue (2% vs 15%); in pts with non-functional NET, grade 3/4 AEs included hypertension (21% vs 4%) and fatigue (18% vs 4%). Conclusions: Subset analyses of the CABINET trial suggest that CABO is an effective treatment option for pts with functional and non-functional epNET or pNET. Efficacy and safety results for pts with functional or non-functional NET treated with CABO are consistent with results for the entire trial. Clinical trial information: NCT03375320 .