Kim, Chul

Abstract Background There is limited data on immune checkpoint inhibitor (ICI) use in patients with non-small cell lung cancer (NSCLC) and known pericardial effusions. Methods This international multi-center observational retrospective study included patients with advanced NSCLC with or without pericardial effusions receiving ICIs. Immune-related adverse events (irAEs) were graded per CTCAE v5.0. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Cox proportional hazards multivariable models assessed the association between survival outcomes and clinicopathologic variables, and an inverse probability of treatment weighting (IPTW) model compared outcomes between the two groups. Results A total of 1248 patients with advanced NSCLC treated with ICIs across 13 institutions were included. Of these, 85 patients (6.8%) had pre-existing pericardial effusions. Compared to controls, patients with pericardial effusions were younger (median age 63 vs 67 years, P = .007), diagnosed more frequently with PD-L1 positive tumors (96% vs 76%, P < .001), and had a higher median number of baseline metastatic sites (3 vs 1, P < .001). IrAEs were similar between both groups (42% vs 38%), and no cardiac irAEs occurred in patients with pericardial effusions. PFS (median 5.6 vs 4.6 months, P = .3) and OS (median 10.2 vs 14.7 months, P = .50) were not statistically different between patients with pericardial effusions and the controls, respectively. In both multivariable and IPTW models, pericardial effusions were not associated with PFS or OS. Conclusions Among patients with NSCLC and pre-existing pericardial effusions, ICIs demonstrate meaningful clinical benefit similar to those without effusions, with no new cardiac or severe toxicities.

8019 Background: Neoadjuvant and perioperative chemo-immunotherapy studies report 15%-20% of pts initiating NACT-I do not undergo surgical resection. Methods: Real-world data of pts who initiated NACT-I was collected retrospectively for January 1 st 2022 till September 30 th 2024. Pts and treatment details, reason for not undergoing resection (as assessed by the clinicians) and later treatments and outcomes were recorded. Total number of pts who initiated NACT-I in this period was identified from each center's records. Missing data was not imputed. Results: Data was collected from 10 centers in 4 countries (USA, Israel, Switzerland, France). Out of 330 pts that started NACT-I 43 pts (13%; range 4-33% in different centers) did not undergo surgical resection. Of these 43 pts, 34.9% became unresectable due to disease progression (PD). 20.9% in retrospect were non-resectable and did not regress as expected. 11.6% in retrospect were non-operable. 11.6% suffered toxicity and became unfit for surgery. 7% of pts refused surgery, 14% were not resected for other reasons (Table). Of the non-resected pts, 9.3% died prior to any second-line treatment. As a second line, 44.2% of the non-resected pts were treated with chemo-radiation, 14% with radiation alone, 7% chemotherapy and immunotherapy, 4.7% immunotherapy alone and 2.3% chemotherapy alone. 7% received palliative radiation followed by chemo or immunotherapy, 7% had follow-up alone. Conclusions: The rate of no surgical resection in this real-world multi-national cohort was 13%, in line with the rate in reported studies. Most un-resected pts underwent appropriate staging. Most were male, with high rate of T3/T4. Survival rate at 12 months was 73.7%. The most common causes for no surgery were PD or being upfront unresectable. The patients with the worst outcome were those who experienced PD during NACT-I. N (% out of 43 non-resected) Male (%) Age (median) PET Done prior to any therapy (%) Brain MRI staging (%) Documented MDT decision of NACT-I (%) Documented surgeon evaluation prior to NACT-I decision (%) T3-4 (%) N2a/b (9th V TNM; %) Survival rate at 12 month (95% CI) 43 (100.0) 69.8 71 95.3 95.0* 96.6* 86.2* 69.8 40.5 73.7% (50.5-87.2%) PD 15 (34.9) 80.0 67 93.3 100.0* 100.0* 92.3* 80.0 40.0 68.2% (14.2-89.7%) In retrospect not resectable 9 (20.9) 55.6 69 100.0 100.0 100.0* 50.0* 77.8 33.3 76.2% (33.2-93.5%) In retrospect not operable 5 (11.6) 80.0 71 100.0 60.0 100.0* 33.3* 40.0 20.0 100.0% (100.0-100.0%) Toxicity 5 (11.6) 80.0 72 100.0 100.0 100.0* 100.0* 80.0 80.0 80.0% (20.4-96.9%) Patient refusal 3 (7.0) 0.0 72 100.0 100.0 100.0 100.0 66.7 33.3 100% (100.0-100.0%) Other ** 6 (14.0) 83.3 75 83.3 100.0* 75.0* 100.0 50.0 40.0* 50.0% (11.1-80.4%) Percentages relate to the total of each row, besides 1st column relating to total of 43. *% of available data. **Death (n=3), intra-operative decision (n=2), additional malignancy (n=1).

Abstract Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung tumor marked by significant molecular heterogeneity. In a study of 590 patients across two independent cohorts, we observed comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events. Genomic analysis identified distinct NSCLC-like (KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations) LCNEC subtypes, with 80% aligning with SCLC transcriptional profiles. Serial sampling revealed stable mutational but shifting transcriptomic landscapes over time. NSCLC-like LCNECs showed elevated FGL-1 (a LAG-3 ligand) and SPINK1 expression, while SCLC-like subtypes expressed higher levels of DLL3. Immunofluorescence confirmed FGL-1 in NSCLC-like LCNECs, and H&E slide analyses indicated fewer tumor-infiltrating lymphocytes in LCNECs versus other lung cancers. These findings highlight LCNEC’s distinct immunogenomic profile, supporting future investigations into LAG-3, SPINK1, and DLL3-targeted therapies.

Background Data on the safety profiles and clinical outcomes of patients with solid tumors and cardiac metastasis treated with immune checkpoint inhibitors (ICIs) are limited. Methods This is an international multicenter retrospective study of patients with cancer and cardiac metastasis at baseline. Patients who had received ≥1 dose of ICI were included. Treatment-related adverse events (trAEs) were graded per Common Terminology Criteria for Adverse Event V.5.0. Objective response rates (ORR) were evaluated by Response Evaluation Criteria in Solid Tumors V.1.1 when available. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Results Among 110 pts, median age at ICI initiation was 65 (IQR: 59–75). Median follow-up time since ICI initiation was 36 (95% CI: 26 to 51) months. Melanoma (38%, n=42) and non-small cell lung cancer (24%, n=26) were the most common. 68 (62%) patients received ICIs as first-line, and 29 (26%) patients were treated with combination anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen 4. The most common location of cardiac metastasis was in the atria (37%, n=41) and ventricles (35%, n=39). 15 patients (13.6%) had bilateral cardiac/pericardial metastasis, 44 (40%) had left-sided, and 43 (39.8%) had right-sided. At ICI initiation, 21% (n=23) had a cardiac thrombus. Cardiology referrals and cardiac MRIs at the time of cancer diagnosis were completed on 58 (53%) and 52 (47%) patients, respectively. Cardiac events occurred in 40 (36%) patients, including arrhythmias (n=14, 13%), arterial/venous emboli (n=4, 3.6%), and cardiac tamponade (n=3, 2.7%). 53 (47%) patients developed trAEs; most common were colitis/diarrhea (n=16, 15%), dermatitis (n=13, 12%), and hepatitis (n=9, 8.2%). ICI-related major cardiac trAEs occurred in 2 (1.8%) patients. 22 patients (20%) developed grade ≥3 trAE. Patients with multiple cardiac metastases had significantly lower responses to ICI-based regimens compared with patients with single cardiac metastasis (11% vs 63%, p=0.02). For melanoma, ORR, median PFS, and median OS were 38%, 9.0 months, and 28.9 months, respectively. 83% of patients with melanoma had concordant responses in overall disease burden and cardiac disease. 91 patients discontinued ICIs, and the main reason was progression or death in 55 (49%) patients. Conclusions Among patients with pre-existing cardiac metastasis, ICIs demonstrated meaningful clinical efficacy with no increase in safety signals. Most patients had concordant responses in the overall disease burden and cardiac mass. Multidisciplinary teams are crucial for the appropriate management of patients with cardiac metastasis.

8106 Background: Due to lack of prospective data, the optimal first line treatment approach for patients (pts) with pure LCNEC histology remains uncertain. Methods: Across 17 centers, we conducted a retrospective analysis of metastatic pure LCNEC (diagnosed at local institutions) who received 1st-line systemic therapy between 2015-2023. Pts were either treated with chemotherapy (chemo), immunotherapy (IO), or a combination (chemoIO). Clinical outcomes were progression-free survival (PFS), overall survival (OS), objective response rates (ORR), and treatment-related adverse events (trAE) as defined using CTCAE 5.0. Survival analysis by genomic alteration status ( TP53, RB1, STK11, KEAP1, KRAS) and PD-L1 status were performed. Results: We identified 161 pts with median age of 67 years (IQR: 58-83) at 1st line systemic therapy; 54% (n = 87) were males. Median follow-up was 55 months (mo), 62 mo, and 29 mo for the chemo, IO, and chemoIO groups, respectively. 79% (n = 127) were former or current smokers. 1st-line treatments were chemo (n = 94), IO (n = 11), or chemoIO (n = 56). Of 85 pts with PD-L1 status, 58 (68%) were 0% and 27 (32%) were ≥1%. The most common chemo regimen was platinum-etoposide (n = 72, 78%). ChemoIO regimens included carboplatin/etoposide/atezolizumab (n = 23, 43%) and carboplatin/pemetrexed/pembrolizumab (n = 17, 31%). In the IO group, 1 patient received dual IO. Lung (n = 74, 46%) and liver (n = 71, 41%) were the most common sites of metastasisThere was no significant difference in PFS across the groups (median PFS [mPFS] chemoIO: 5.7 mo, 95% CI: 5.0-6.3, chemo: 5.1 mo, 95% CI: 3.1-5.9; IO: 3.6 mo, 95% CI: 1.7-6.5) on multivariable analysis adjusting for ECOG and “M” stage (p = 0.2 and 0.24 for chemoIO-chemo and chemoIO-IO comparisons, respectively). There was no difference in OS (mOS chemo: 11 mo, 95% CI: 7.6-17.4; IO: 13.6 mo, 95% CI: 5.9-not reached; chemoIO: 12.2 mo, 95% CI: 7.4-20.6, p = 0.5 and 0.8 for chemoIO-chemo and chemoIO-IO comparisons, respectively). ORR was 35.2% (31/88) in chemo, 25% (2/8) in IO, and 35.7% (20/56) in chemoIO ( p= 0.46). There were no significant differences in PFS and OS outcomes by treatment group when divided by genetic profile (n = 79, methods), or by PD-L1 status (0% vs ≥1%). Any grade trAE occurred in 48 (51%), 5 (45%), and 28 (50%) pts treated with chemo, IO, and chemoIO, respectively. Grade ≥3 toxicity profiles are shown (table). Conclusions: For 1st-line treatment of LCNEC, similar PFS, OS, and ORR were seen for chemo, IO, and chemoIO. This questions the added benefit of chemoIO compared to chemo alone, and warrants future clinical trials to discern the optimal 1st line treatment. [Table: see text]

PURPOSE Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS This retrospective study included PWH treated with anti–PD-1- or anti–PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti–PD-1/anti–PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was –0.06 months (95% CI, –5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, –4.02 to 8.48; P = .48) for OS. CONCLUSION Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.