Majority Of Pts Research Articles

Real-world overall survival (OS) of patients (pts) with metastatic urothelial carcinoma (mUC) receiving first-line (1L) systemic therapy (tx): Results from IMPACT UC II.

529 Background: Urothelial cancer (UC) is the most common urinary system cancer. The IMPACT UC II study aimed to assess tx patterns and clinical outcomes in pts with mUC treated with platinum-based chemotherapy or immuno-oncology monotherapy (IO-mono) in 1L. Methods: This was a retrospective claims analysis of pts diagnosed with mUC from July 2015 to June 2020 and continuously enrolled for 6 mo before and ≥6 mo after index date (ie, date of first claim) using Optum Research Database, which represents ≈8% of commercially insured and 18% of Medicare Advantage (MAPD) populations. Pts were followed up until disenrollment, study end in August 2021, or death. Analyses examined OS and time to 2L tx (TT2L) in three tx cohorts: cisplatin (cis)-based, carboplatin (carbo)-based, or IO-mono. Results: Of 3,006 pts diagnosed with mUC, 1,037 received 1L tx: 365 (35.2%) with cis-based tx; 337 (32.5%) with carbo-based tx, and 335 (32.3%) with IO-mono. Among treated pts, mean age was 72.5 years (SD, 9.9 years), 72.3% were male, and 77.4% were MAPD insured. At baseline, pts receiving cis-based tx had a lower percentage of ≥3 comorbidities (defined by National Cancer Institute criteria): cis-based, 22.2%; carbo-based, 39.5%; and IO-mono, 45.1%. Among 290 pts (27.9%) receiving 2L tx, carbo-based tx had the shortest median TT2L (5.7 mo). Pts receiving cis-based tx had the longest median OS (27.4 mo). Relative to cis-based tx, multivariable–adjusted mortality risk was 2 times higher with IO-mono (hazard ratio [HR], 2.0; 95% CI, 1.6-2.5) and 1.5 times higher with carbo-based tx (HR, 1.5; 95% CI, 1.3-1.9) (Table). Conclusions: This study shows that, before avelumab 1L maintenance approval, the majority of pts did not receive any systemic anticancer tx. following mUC diagnosis. In 1L, after multivariable adjustment (including for baseline comorbidities), real-world OS was lower in pts receiving carbo-based tx and IO-mono compared with cis-based tx. Future research should examine outcomes with newer standard of care.[Table: see text]

Sintilimab, SBRT and GM-CSF for Metastatic NSCLC: A Prospective, Multicenter, Phase II Trial

PD-1/PD-L1 inhibitors have transformed the therapeutic landscape in metastatic non-small cell lung cancer (NSCLC). However, the objective response rate (ORR) remains limited in unselected population. Incorporating SBRT to PD-1/PD-L1 inhibitors may improve treatment efficacy and the anti-tumor immunity induced by SBRT may be enhanced by GM-CSF, which plays a pivotal role in dendritic cell differentiation and maturation. The current trial (NCT04106180) is the first prospective, multicenter, phase II study assessing the safety and efficacy of a PD-1 inhibitor (Sintilimab), SBRT and GM-CSF in metastatic NSCLC patients without sensitizing driver mutations. Metastatic EGFR/ALK negative NSCLC pts who had failed first-line standard chemotherapy were eligible. Pts received SBRT (8 Gy*3) to one lesion, followed by Sintilimab (200 mg d1, every 3 weeks) and GM-CSF (125 μg/m2 d1-d14, cycle 1) within 3 weeks after SBRT. Sintilimab would be given continuously until disease progression, unacceptable toxicity, or up to 35 cycles. Primary end point is ORR. Secondary end points are safety, out-of-field response rate, overall survival (OS), progression free survival (PFS). The trial was designed to enroll 56 patients and if ≥17 pts evaluated had an objective response, it was regarded as positive. By the time of 2022/10/30, the trial was early closed after 18 of the 51pts enrolled from 6 academic centers documented PR. The majority of pts were male, ECOG 1 and non-squamous NSCLC, having more than 5 lesions at baseline, with a median age of 62 (range, 32-74). The sites of SBRT included lung (n = 20), regional lymph node (n = 16), pleural nodule (n = 5), vertebra (n = 3), distant lymph node (n = 3), liver (n = 2) and others (n = 2). Treatment-related adverse event (TRAE) occurred in most pts and grade 3 TRAE occurred in 6 (11.8%) pts. No grade 4-5 TRAE occurred and the most common grade 3 TRAEs were ALT/AST elevation (n = 2), transient acute heart failure (recovered within 7 days) (n = 1), leucopenia/neutropenia (n = 2), pneumonitis (n = 1) and creatinine elevation (n = 1). With a median follow-up of 19.2 (range, 4.6-35.4) months, 49 pts had evaluable efficacy, with 18 PR, 15 SD and 16 PD. Median PFS and OS were 5.9 (95% CI, 3.9-9.2) and 16.2 (95% CI, 12.6-34.1) months, respectively. The results of biomarker testing will also be presented. Triple combination of Sintilimab, SBRT and GM-CSF is safe and shows promising efficacy in metastatic EGFR/ALK negative NSCLC.

CT-based radiomics model for the prediction of genomic alterations in renal cell carcinoma (RCC)

Abstract Background Radiogenomics is an emerging tool with applications in screening for molecular biomarkers in diagnostic and prognostic assessment through the extraction of quantitative data from medical images (Shui et al., Front Oncol 2021). In this study, we aim to develop machine learning (ML) models to predict the most common genomic alterations present in our subset of renal cell carcinoma patients (pts). Methods Retrospectively, pts with tissue genomic testing from CT-guided biopsy samples were identified. Genomic testing was done via GEM ExTra assay, a CAP-accredited, CLIA-certified test encompassing tumor whole exome sequencing and whole transcriptome sequencing (TGen; Phoenix, AZ). Biopsy sample collection sites were identified from pre-biopsy contrast CT images, and the lesions were segmented with ITK-SNAP software, from which 510 radiomic features were extracted with Pyradiomics. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select the most relevant features. Logistic regression (LR) and support vector machine (SVM) classifiers were built for the prediction of PBRM1, VHL, and SETD2 gene alterations. Multiple metrics were used to evaluate the predictive performance via leave-one-out cross-validation, including the area under the receiver operating characteristic (AUROC) and the area under the precision-recall curve (AUPRC). Feature importance was evaluated with Shapley additive explanations (SHAP) method. Results A total of 14 RCC pts (10:4 M:F) with genomic testing from CT-guided biopsies were identified. The majority of pts were White (85.7%) and had clear cell histology (71.4%). The most common locations for the CT-guided biopsy were lung (18.2%), soft tissue (13.6%), kidney (9.1%), and bone (9.1%). The most common alterations were seen in PBRM1 (50%), VHL (43.9%), and SETD2 (35.7%) genes. The PBRM1 gene was predicted with the highest AUROC (0.84) and AUPRC (0.88) with the SVM classifier, followed by the SETD2 gene (AUROC=0.78 and AUPRC=0.66) with LR classifier and VHL gene (AUROC=0.56 and AUPRC=0.65) with SVM classifier. Notably, all three models showed good sensitivity in classifying gene mutation status (PBRM1: 0.86; VHL: 0.88; SETD2: 0.89). Among all radiomic features, first-order features, Gray Level Size Zone Matrix features, and Gray Level Dependence Matrix features were found to be the most important features for predictions. Conclusions Using a CT-based radiomics analysis of the biopsy area, we showed that SVM and LR prediction models could predict PBRM1, VHL, and SETD2 mutations with high accuracy. These models may assist in identifying potentially actionable alterations and yield ease in treatment selection for RCC. Further extensive studies are warranted to validate our findings and improve our model. CDMRP DOD Funding: no

82-LB: Effectiveness of Coordinated and Centralized Care for Insulin Pump Users—A Multiple-Year Cohort Study

Background: With >13000 children diagnosed with type 1 diabetes each year, it imposes a tremendous burden on US healthcare. However, data are scarce on management models for pump users. Methods: In this observational cohort study, patients (pts) were systematically monitored for 4 years at our centralized & coordinated pump center. Data on both outcome measures (percentage of glycated hemoglobin, or A1C) & pt characteristics were routinely documented. Results: For all study pts (n=219), a statistically significant reduction in A1C was observed (-0.4% A1C; 95% CI: -0.7-0.1%). And this is true for all three groups of pts disaggregated by initial A1C (7.5-10, 8.0-10, ≥10). The reduction was -0.6 (95% CI: -0.8-0.3) for ps with a starting A1C between 7.5-10; -0.8 (95% CI: -1.1-0.5) for pts with a starting A1C of 8.0-10; and -2.4 (95% CI: -3.4 -1.3) for pts with a starting A1C above 10. A majority of pts reached their target A1C levels, and most of them achieved that in first quarter after the installation of insulin pumps (See Fig 1). Conclusions: Through centralized and coordinated care, a pump center is effective in assisting diabetes patients in properly using insulin pumps and quickly achieving their target A1C levels. Given the heavy burden of diabetes and large number of insulin pumps, the model of a pump center may be able to help confront the disease burden, and therefore needs to be made available to more patients. Disclosure K. Latif: Research Support; Medtronic, Senseonics. Board Member; Bigfoot Biomedical, Inc. Q. Li: None. Y. Shaikh: None. F. H. Cheema: None. A. Hyder: None.

IND227 phase III (P3) study of cisplatin/pemetrexed (CP) with or without pembrolizumab (pembro) in patients (pts) with malignant pleural mesothelioma (PM): A CCTG, NCIN, and IFCT trial.

LBA8505 Background: The vast majority of pts with PM have unresectable disease, due to co-morbidities and/or advanced stage. In unresectable PM, standard first line treatment has been C(or carboplatin)P for 20 years but it is usually only moderately efficient, mostly on epithelioid (E)PM, with a global median overall survival (mOS) around 12 months (m), an improved quality-of-life (QoL), and mild toxicity. Trial CM743 demonstrated a significant improvement in mOS for nivolumab/ipilimumab (NI) over CP (18.1 versus 14.1 m), particularly for non-EPM, but 30% NI pts experienced > grade 3 toxicity. Thus, alternative therapies to improve mOS and tolerability are needed. Methods: Canadian Cancer Trials Group (CCTG) IND 227 is an academic, open-label, randomized P3 study of the CCTG, National Cancer Institute of Naples (NCIN) and Intergroupe Francophone de Cancérologie Thoracique (IFCT). The study was supported by grants to CCTG (Canadian Cancer Society -707213); Merck & Co. Inc provided pembrolizumab (pembro) and a grant to support study conduct. Untreated unresectable PM pts ≥ 18 years with ECOG performance status 0-1, adequate hematological, renal and hepatic function, no active autoimmune disease, brain metastases, interstitial lung disease or other active co-morbidities, were randomized 1:1 to CP with or without pembro and stratified by histology (E vs. non-E). Carboplatin was allowed if C contraindicated. Radiological review (BICR) and PD-L1 testing was centralised. mOS was the primary endpoint; median progression-free survival (PFS) and response rate (RR), QoL (EORTC QLQ-C30 + QLQ-LC13) and economic analysis were secondary. Results: A total 440 PM pts were randomized; 218 to CP and 222 to CP-pembro. Data cut-off was 16 September 2022 when the required events was observed. All pts were included in the analyses. Arms were well balanced. Seven pts opted not to receive CP. Median exposure of CP was comparable between arms. Subsequent treatment with chemotherapy was similar in both arms, while 59 pts in CP arm (vs 17 CP-pembro pts) received immunotherapeutics. Using a stratified log rank test, mOS was 17.3m vs 16.1m for CP-pembro vs CP (HR 0.79 95%CI 0.64-0.98; p=0.0324), mPFS was 7.13m vs 7.16m (HR 0.80, 95%CI 0.65-0.99, p=0.0372). BOR was significantly higher for CP-pembro (63% vs 40%, p < 0.0001). Grade 3 or higher pembro related adverse events (AEs) occurred in 19% of patients (88% were grade 3; the most common were fatigue (5%) and diarrhea, pneumonitis and irAE (2% each)), and 16% of pts discontinued pembro per protocol for related AEs (most commonly diarrhea and pneumonitis). Conclusions: With a statistically significant improvement in mOS and acceptable tolerability. CP-pembro is an option for treatment naïve, unresectable PM. Clinical trial information: NCT02784171 .

Real-world behavioral restrictional practices of cancer patients (pts).

6592 Background: Quality of life (QoL) assessments do not measure pts’ ability to maintain normal daily activities during cancer therapy. Misbeliefs might promote avoidance of activities perceived as dangerous, compromising pts QoL. We examined the daily practices of actively treated pts with cancer. Methods: A locally validated questionnaire at the Tel-Aviv Sourasky Oncology Division was distributed internationally using the Belong.life social and professional digital health platform. We examined real-world pts reported practices, provided voluntarily and anonymously. The survey consisted of 15 questions, including demographic, clinical, behavioral parameters and sources guiding and supporting pts practices. Independent clinical and demographic variables were analyzed. Statistical analysis was performed, and a multivariate logistic regression was conducted to identify factors predicting restrictive behaviors. Results: The study population comprised 1,395 pts receiving active cancer therapy, reporting their outcomes from the Belong digital platform. Most respondents were from the United States (1082, 77.70%) and Israel (223, 16%), over the age of 40 (1309,93.8%),and female (987, 70.75%). Most common tumor types were breast (394,28.24%) and gastrointestinal cancers (199,14.26%). The majority of pts (1,005,72.88%) reported on at least 1 adopted limitation in daily activities, and 305 (21.86%) maintained more than half of these constraints. Daily life restrictions included avoiding sun exposure (779, 57.83%), international travel (417, 33.33%), indoor public places (malls, etc) (431, 33.13%), hair dyeing (271, 22.72%), domestic tourism (284, 21.93%), contact with friends and family (231, 17.69%), children and grandchildren (202, 16.33%), outdoor public spaces (190, 14.62%), and contact with pets (135, 10.41%). Multiple sources were implicated by the pts as guiding their behavior, with the most common being health-care professionals (951, 65.95%), followed by both non-medical authorities and health-care team (320, 22.19%), and non-medical advisors, including internet, pts forums, partners, friends, and family (171, 11.86%) Pts who maintained strict (≥50% of the limitations) and less strict restrictions, demonstrated no significant association between country of origin (p = 0.118), and education level (p = 0.3591). A significant association was noted between younger age (p = 0.0014), female sex (p = 0.0141) and primary cancer site (p < 0.0001), and the adoption of strict restrictions. Conclusions: The majority of pts reported compromised daily activities, which are likely attributed to misconceptions about therapy and disease, deleteriously impacting QoL, therefore, impeding their ability to continue to conduct a complete and meaningful life. These findings require development of tools examining patients’ real-daily life activity as an additional endpoint in clinical trials.

Baseline endogenous serum testosterone levels and all-cause mortality in men with prostate cancer treated by radical radiotherapy: 11-year follow-up data.

e17003 Background: Low levels of serum testosterone are associated with higher all-cause mortality and cardiovascular mortality in some studies.(PMID: 18040028). But men with low levels of serum testosterone at reduced risk of developing prostate cancer. (PMID: 30077399). In middle-aged and elderly men, single point testosterone measurements have been shown to reliably reflect long term androgen exposure. [PMID: 1548361]. We assessed the interaction of pre-treatment serum testosterone levels and long term all-cause mortality in men with newly diagnosed prostate cancer. Methods: Prostate cancer pts enrolled in an ethics approved, prospective study evaluating a rating scale. Baseline serum testosterone levels were measured before the pts were commenced on androgen deprivation therapy and radical radiotherapy. Patient characteristics: Mean age 68.2yrs (median 69yrs); Age range category < 60yrs:14.9% , 61-70yrs:47.3% and > 71 yrs: 37.8%. Charlson Comorbidity Index (CCI) prevalence at baseline as follows CCI- Low risk : 39.9%; CCI-medium risk : 51.4%; CCI-high risk: 8.8%. PSA median level was 10.85 ug/L. Tumour was localised in a majority of pts- stage T1/T2 in 72% . Pts with M1 disease were not enrolled. Histology grade: Gleeson grade 6 in 7.4% and Gleeson grade 7 in 53.4% . Serum testosterone: Median 11.9 nmol/l; Mean 12.4 (Min-Max 2.6 to 26.7). Cox proportional hazards regression used to analyze the effect of baseline Serum Testosterone on long term overall survival, while controlling for covariates (age, cancer T stage, PSA category, Gleeson Category and Charlson Comorbidity index). Results: Lower levels of serum testosterone at baseline were associated with decreased all-cause mortality. There was no significant correlation between testosterone levels and age in our study sample of relatively elderly population (Pearson Correlation p = 0.362); There was no correlation testosterone levels and PSA levels(P = 0.821); no association between serum Testosterone levels and Gleeson Grade as well as T stage. (F = 0.78 ; P = 0.46 and F = 1.34 ; P = 0.26 respectively). There was also no significant variation in testosterone levels according to Comorbidity categorised by Charlson Comorbidity Index. (F = 1.31 P = 0 .26). Conclusions: Lower Serum testosterone levels were associated with decreased all-cause mortality in this prospectively collected survival data of non-metastatic Prostate cancer patients. [Table: see text]

Real-world (RW) treatment and surveillance patterns in patients with hepatocellular carcinoma (HCC) after resection (R) or ablation (A): Evidence from commercial and Medicare populations.

e16223 Background: Prognosis of early HCC after curative resection (R) or ablation (A) remains poor due to lack of approved standard of care for adjuvant therapy. Guidelines recommend that patients (pt) receive surveillance imaging every 3 to 6 months for the first 2 years after R or A. RW data on treatment and surveillance patterns after curative intent therapy in the US can provide insights into how novel therapies may be integrated into the treatment paradigm. Methods: We conducted two retrospective, population-based studies of newly diagnosed HCC pts who underwent R or A as the first HCC therapy using data from Pharmetrics Plus commercial claims (2018 - 2021) and SEER-Medicare data (2010 - 2019), respectively. Continuous enrollment in health plans ≥6 months prior to diagnosis (Dx) date and ≥3 months after R or A, and no transplant during study period, was required. Treatments received within 3 months following R or A were defined as adjuvant therapy. Results: Among 705 eligible HCC pts with commercial insurance coverage, the majority were male (73%) and mean (SD) age at Dx was 61(9) years. Among them, 56% received A, 32% received R, and 12% had both R and A after Dx. 126/705 (18%) pts received adjuvant therapy. Most commonly used treatments were systemic therapy (44%) followed by transarterial chemoembolization (TACE) or transarterial embolization (TAE) (41%). Only 20% of pts received surveillance imaging in the first 2 years following R or A (Table). A total of 2,005 Medicare beneficiaries with HCC were identified from SEER-Medicare (male: 67%; White: 68%; Black: 11%; Asian: 19%). Mean (SD) age at Dx was 70(8) years. Among them, 54% received A, 36% received R, and 10% received both as the initial therapy for HCC. 238/2,005 (12%) pts received adjuvant therapy. Most commonly used treatments were TACE/TAE (61%) followed by systemic therapy (29%). Unlike the commercial insurance cohort, the majority of pts in the Medicare cohort (78%) received surveillance imaging within 2 years following R or A. Conclusions: Despite lack of clinical evidence and approved adjuvant therapy in the US, notable use of treatment in RW practice were observed. Types of adjuvant therapy used and utilization of surveillance varied by payers. A significant proportion of pts did not receive ongoing surveillance imaging despite guideline recommendations. These findings highlight the desire and unmet need for clinical evidence of treatments in pts with early HCC following curative intent therapy. [Table: see text]

Genomic profiling in advanced NSCLC in Italy: First results of NERoNE (NSCLC Emilia Romagna Next Generation Sequencing Evaluation) project.

e21077 Background: The NERoNE Project evaluates the use of Next Generation Sequencing (NGS) in molecular profiling of advanced NSCLC (aNSCLC) patients (pts) in three Oncology Units (OU) of Emilia Romagna Region aiming to clarify the impact of such extensive tool in characterizing different NSCLC subpopulations. Methods: Since January 2020 to December 2022, 970 sequential aNSCLC pts from three OU (AUSL-IRCCS of Reggio Emilia, Modena University Hospital and IRST Meldola) were profiled by NGS. Samples from Modena and Reggio Emilia were analyzed at Modena University Hospital Molecular Pathology Lab using Myriapod IL- 56G, Cancer Panel DNA, Cancer Panel RNA, Oncomine DX Target Test Assay, Oncomine Focus Assay. Samples from IRST Meldola were processed at its Molecular Diagnostic Unit by Myriapod NGS cancer panel DNA e RNA, Oncomine Focus Assay and Oncomine Comprehensive Assay v3.We considered molecular alterations with available target therapies in Italy: EGFR mutations (mut) (exon 18,19,20,21), KRAS mut, BRAF V600E mut, ALK, ROS1, RET and NTRK rearrangements, MET exon 14 skipping mut, ErbB2 mut, FGFR 1-3 mut. PDL1 expression was assessed by standard immunohistochemistry on 486 pts. Results: Among 970 pts, 501 with at least one mut (52%) were considered for analysis: 266 were female (53%), mean age was 69 ± 11 years (min-max: 33-94) and 473 pts (94%) had adenocarcinoma. Molecular features are listed in table 1. Distribution of mut among ages, categorized as < 60, 60-70 and > 70 y, was similar, EGFR activating mut were most prevalent in females; KRAS mut (G12C and non G12C) were most prevalent in males; 41 pts had co-mutations (8.2%): the most frequent co-mut were EGFR mut (27%). PDL1 expression was < 1% 129 (27%), 1-49% 211 (43,4%) and ≥50% 146 pts (30%). The majority of pts with EGFR activating mut had PDL1 < 50%. Conclusions: NERoNE evaluates data from NGS profiling of three OU mapping key actionable molecular alterations in a large population of aNSCLC also accounting for PDL1 status. This preliminary analysis will be the starting point for further evaluations in order to improve the personalized approach to aNSCLC. [Table: see text]

Durable clinical outcomes in patients (pts) with advanced melanoma and progression-free survival (PFS) ≥3y on nivolumab (NIVO) ± ipilimumab (IPI) or IPI in checkmate 067.

9542 Background: NIVO + IPI has demonstrated durable clinical benefit at 7.5 y in pts with advanced melanoma in the phase 3 CheckMate 067 study. PFS curves plateaued at ~3 y in this study, suggesting that being alive and progression-free for ≥ 3 y (PFS ≥ 3y) may be a good surrogate for long-term clinical benefit. We conducted analyses to quantify this association. Methods: Pts with treatment (tx)-naive, unresectable stage III/IV melanoma (stratified by PD-L1 expression, BRAF mutation status, and metastasis stage) received NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W, followed by NIVO 3 mg/kg Q2W (n = 314); NIVO 3 mg/kg Q2W + placebo (n = 316); or IPI 3 mg/kg Q3W for 4 doses + placebo (n = 315) until progression or unacceptable toxicity. Exploratory post hoc analysis was performed in pts with PFS ≥ 3y. Results: In the NIVO + IPI, NIVO, and IPI arms, respectively, 99 (32%), 78 (25%), and 21 (7%) pts had PFS ≥ 3y. Objective response rates (ORRs) in these pts were ≥ 95% (table). The majority of responses were complete responses (CRs; table); in almost all pts with partial responses (PRs) on NIVO + IPI or NIVO, target-lesion size decreased by ≥ 50%. At 7.5 y of follow-up among pts alive and progression-free at 3 y, PFS rates were ≥ 68%, overall survival (OS) rates were ≥ 85%, and melanoma-specific survival (MSS) rates were ≥ 95% in the 3 tx groups (table). Among pts in this group who died after 3 y on study, the majority of deaths were unrelated to disease (table). The majority of pts with PFS ≥ 3y who were alive and in follow-up were tx-free at the 7.5-y data cutoff (77/84, 57/64, and 13/16). Pts who received NIVO + IPI were off tx (median) for 75.5 mo (NIVO, 55.7 mo; IPI, 59.2 mo). Among pts with PFS ≥ 3y in the 3 tx groups, 4%, 5%, and 19% received subsequent systemic tx (table). No new safety signals were observed in pts with PFS ≥ 3y. Conclusions: This exploratory post hoc analysis suggested that PFS ≥ 3y may be a good surrogate for long-term MSS with NIVO + IPI or NIVO, with very few occurrences of progression or death due to melanoma in this population through 7.5 y. Most pts were tx-free without having received subsequent systemic tx after demonstrating PFS ≥ 3y. Further study of pts with PFS ≥ 3y may allow the burden of imaging and follow-up visits to be reduced in this group. Clinical trial information: NCT01844505 . [Table: see text]

Co-mutational status and PD-L1 expression in KRAS mutant non-small cell lung cancer (NSCLC): Role in treatment selection and association with clinical outcomes.

9038 Background: In NSCLC, different KRAS mutations (mt) define unique subgroups and certain co-mutations (co-mt) could have prognostic and therapeutic implications. Retrospective studies associate poor prognosis with co-mts in STK11 and KEAP1 with KRAS. It is unclear if PD-L1 expression and co-mt in KRAS mt NSCLC impacts outcomes. Methods: Molecular profiles of 27748 NSCLC tumors were tested with next-generation sequencing (Caris Life Sciences, Phoenix, AZ) and classified by KRAS mt. PD-L1 IHC (22C3) was reported as TPS. Real-world post-immunotherapy (IO) overall survival (OS) was obtained from insurance claims and calculated from start of an immune check-point inhibitor (with or without chemotherapy) to the last day of follow-up. Results: In all, 7634 (28%) samples had a KRAS mt; most common being G12C (11%), G12V (5.3%), G12D (3.9%) and G13X (2.0%). The most frequent co-mt was KRAS-TP53 (KP) (46%), similar in all KRAS subtypes. KRAS-STK11(KL) was in 23% of KRAS mt, enriched in G13X (33%) and lowest in G12D (16%). KRAS-KEAP1(KK) was co-mt in 10% of KRAS mt, highest in G13X (16%) and lowest in G12D (8%). KRASmt/ STK11wt/ KEAP1wt/ TP53wt (K only) was 27% of KRAS mt, highest in G12D (36%) and lowest in G13X (16%). A small subgroup, 5.6% was KRAS-STK11-KEAP1 co-mt (KKL). The majority of pts in the KL (61%), KK (52%) and KKL (62%) cohorts had TPS <1%. In 1723 KRAS mt NSCLC pts treated with IO, KL, KK and KKL had significantly worse post-IO OS than KP and K only (table); KKL had the lowest OS. In the TPS≥1% KRAS mt group, KL, KK and KKL had worse post-IO OS than KP and K-only. In TPS<1% group, KL and KK had poor post-IO OS and K-only had favorable outcomes. However, KP had worse post-IO OS compared to K-only in TPS<1%. In G12C and G12V, similar trend with worse post-IO OS in KL, KK and KKL, compared to KP and K only was noted. Conclusions: We report a large real-world dataset evaluating outcomes with check-point inhibitors in NSCLCs with KRAS and specific co-mts. KL, KK and KKL subgroups demonstrate universally poor outcomes in all KRAS subtypes irrespective of PD-L1. Pts with KP co-mts have adverse post-IO outcomes in TPS<1% but favorable in TPS≥1%. TPS score remains a predictive marker of IO outcomes in KP, but not in KL, KK and KKL. These observations emphasize that both PD-L1 and co-mts have a clear association with clinical outcomes in KRAS-mt NSCLC, and must be used in predictive models for individualized therapy. [Table: see text]

Clinicopathological features and treatment patterns of patients with cancer of unknown primary site (CUP): Mayo Clinic experience.

e18803 Background: CUPs are a heterogeneous group of metastatic cancers for which a standardized diagnostic work-up fails to identify the site of origin at the time of diagnosis. CUP accounts for 3%-5% of all cancer diagnoses worldwide, and the natural history of patient with CUP differs from that of patients (pts) with cancer with known primary tumor. Here we report and summarize the clinical features of patients with CUP treated at Mayo Clinic. Methods: Retrospective study of patients treated at Mayo Clinic Rochester MN from 2010 to 2021. Patient demographics, tumor-related variables, treatment-related variables, and clinical data were extracted. Descriptive statistics were used, and all data were analyzed by the SPSS version 22.0 software (SPSS, Chicago, IL, United States). Results: From a total of 214 pts, 207 pts were included, as primary tumor site was identified in 7 patients after initial evaluation. The pts in this study were predominantly white (87%) of female (50.2%) gender with a mean age of 63 (SD: 13) without history of smoking (51%) and either private or public insurance (82.6%). The predominant histology was adenocarcinoma (30%), followed by neuroendocrine neoplasms (27%), and carcinoma NOS (not otherwise specified) (25%). The most prevalent grade in this cohort was grade III with poorly differentiated tumor cells. All pts had diagnostic imaging and the most used imaging modalities included CT (81.2%), and PET-CT (43.5%). In our cohort, the 3 most common sites of metastases included lymph nodes (57.5%), liver (37.8%), lung (34.3%), and bone (23.7%); and in 64% of pts, there was a specific presentation pattern including liver-predominant (24.6%), lymph node-predominant (24.6%), bone-predominant (7.7%), and peritoneal carcinomatosis (7.7%). The majority of pts received systemic therapy (69%) as first line of therapy and the most frequent first line regimens included platinum-doublet (26.5%), gemcitabine-based regimen (20.7%), 5FU-based regimens (18%) and somatostatin analogs (16.7%); whereas salvage radiation and ablation were offered to 11% of pts and surgery to 17%. The median follow-up time was 22 months (IQR: 45) with a median survival time of 23 months and the 3-year cumulative survival rate was 30%. Conclusions: The heterogenous nature of CUPs and lack of specific immunohistochemical signature prevents primary tissue of origin diagnoses in CUP pts. Without the identification of a primary origin site, treatment is restricted to generic chemotherapy with limited benefit as demonstrated in this cohort.

Real-world analysis of D-RVd v. RVd at induction for newly diagnosed transplant eligible multiple myeloma patients.

e20024 Background: Daratumumab with lenalidomide, bortezomib, and dexamethasone (D-RVd) induction chemotherapy (IC) has recently been shown to improve depth of treatment response for transplant-eligible newly diagnosed multiple myeloma (NDMM) patients (pts) compared to RVd alone. The aim of this real-world data (RWD) retrospective study is to assess the efficacy and depth of response of D-RVd IC compared to RVd in transplant-eligible pts with NDMM. Methods: HealthTree Cure Hub for Multiple Myeloma (PMID: 35271305) an online portal for pts with plasma cell dyscrasias, was used to analyze validated RWD of 59 pts who received D-RVd to 121 pts with similar clinical characteristics but who received RVd at IC. Of the total 180 pts, 84 had completed IC and were at the initiation of maintenance (MT) at the time of this analysis. Patients that progressed prior to reaching MT or whose treatment deviated from the line of therapy (D-RVd/RVd IC, autologous stem cell transplant [ASCT], and MT, with or without consolidation) were also excluded. Response during MT was assessed using IMWG criteria. Results: From the 180 pts reviewed, 98 were excluded, 5 D-RVd and 10 RVD pts progressed before reaching MT, 11 D-RVd and 31 RVd pts deviated from the line of therapy, and 41 pts had not reached the MT phase at the time of the analysis. The remaining 84 pts (18 D-RVd pts and 64 RVd pts) were analyzed. Demographics and clinical characteristics were well-balanced between groups. The median age of both groups was 65 (range, 42-81), and over half were female (51%). The majority of pts (87%) had R-ISS stage I or II, and 45 pts (25%) had high-risk genetics (by mSMART 3.0). The overall response rate (ORR) was significantly higher for the D-RVd group compared to the RVd group at the initiation of MT (100% vs 62%; odds ratio, 22.4; P = 0.03). As assessed prior to the start of MT the depth of response was more favorable with D-RVd, with the odds ratio of achieving a VGPR or better at MT being significantly higher than RVd (89% to 58%; odds ratio (OR), 5.8; P = 0.03), complete response (CR) (78% to 47%; OR, 3.97; P = 0.03), stringent CR (sCR) (22% to 16%; OR, 1.5; P = 0.51), and minimal residual disease (MRD) negativity (17% to 11%; OR, 1.6; P = 0.51). With a median follow-up of 17 months for the D-RVd group (n = 18) and 29 months for the RVd group (n = 64), 0 events of disease progression occurred in the D-RVd group compared to 23 events in the RVd group. Median PFS was not reached in the D-RVd group and a Kaplan-Meier probability indicated a median PFS of 41 months for the RVd group. Conclusions: These data document improved response rate in transplant-eligible NDMM pts who received daratumumab with RVd as an IC therapy. D-RVd also improved PFS with significant differences between the two groups seen at 12 and 18 months. These results add to the accumulating data that the addition of daratumumab with RVd may be the new standard of care for the aforementioned patient population.

Correlation of patient characteristics and tumor histology in patients (pts) with locally advanced cutaneous squamous cell carcinoma (LACSCC) receiving immune checkpoint inhibitor treatment (ICI): A retrospective analysis.

e21553 Background: Cutaneous squamous cell carcinoma (CSCC) arising from epidermal keratinocytes is highly curable with surgery. Functional anti-cancer immunity is protective of CSCC and high mortality due to local or systemic dissemination is seen in pts. with immune deficiency. ICI treatment is a logical FDA approved option that result in improved outcomes in affected pts. We report our experience in LACSCC pts. receiving ICI treatment and describe correlation between pt. characteristics, tumor histology and treatment outcome. Methods: Following Institutional Review Board approval, we did a retrospective analysis of LACSCC pts. receiving ICI therapy at the Neag Cancer Center who received at least one dose of ICI between 2018-2023. Analysis includes pt. demographics, relevant comorbidities, medications, and tumor histology and tumor infiltrating lymphocytes (TILs) of tumors reviewed with dermatopathologist. Results: Between 2018-2023, 12 pts. with LACSCC met the criteria for analysis. Median age 77.5 years (yrs.), (range 65-102), 9 males, 3 females, tumors sites - head and neck region 8 pts., torso 2 pts., legs 2 pts. Relevant past medical history included treatment of prostate cancer 3, chronic lymphocytic Leukemia 1, psoriasis 2 (one received anti TNF treatment), and MGUS, Parkinson’s disease and dementia in 1 each. Majority of pts. had significant smoking history (9/12), lymphopenia in 8 out of 12 pts. Tumors were poorly differentiated in 6 out of 12 pts. Brisk TILs was present in 7 and non-brisk TILs in 5 pts. 3 pts. with brisk TILs achieved complete remission (CR), one very good partial response (VGPR), 1 partial response (PR) and 2 not evaluable for response. Out of 5 pts. with non-brisk TILS, one achieved CR, one achieved VGPR, 1 PR, 1 stable disease (SD), and 1 progressive disease (PD) in a pt. who received anti TNF treatment of psoriasis. 9 patients are alive between 1 week and 50 months after initiation of treatment. 3 pts. died, one of PD, one of bacterial sepsis and one of Covid. Conclusions: High risk LACSCC affected males with smoking histories in the majority. Durable responses following ICI treatment occurred irrespective of age, while resistant disease was noted in 1 pt. with previous anti TNF treatment. Brisk TILs predicted high response rate and durable responses although some pts. with non-brisk TILs also showed favorable outcomes. Association with previous cancer and macular degeneration may reflect underlying immune deficiency. Three pts. developed infection within two weeks of ICI treatment (urinary tract infection, wound infection, Covid). More studies will shed light at factors compounding immune deficiency and safety of this treatment in a high-risk population.

Pelabresib (CPI-0610) monotherapy in high-risk essential thrombocythemia refractory or intolerant to hydroxyurea: Preliminary results from MANIFEST study.

7019 Background: High-risk essential thrombocythemia (HR ET) is characterized by thrombocytosis, thrombohemorrhagic events and systemic symptoms. Pts can experience intolerance, inadequate response or loss of response to first-line cytoreductive therapies (hydroxyurea [HU] or interferon alfa-2a). BET protein inhibition is a novel therapeutic strategy that downregulates inflammatory cytokines and may inhibit differentiation and proliferation of abnormal megakaryocytes involved in ET pathogenesis. Results from the Phase 2 MANIFEST study (NCT02158858) suggested potentially encouraging clinical efficacy in pts with myelofibrosis treated with Pelabresib (PELA), an oral, small-molecule, investigational BET inhibitor. Here we present preliminary results from MANIFEST Arm 4 investigating PELA monotherapy in HR ET refractory or intolerant to HU. Methods: Eligible pts had platelets > 600 x 109/L and ≥ 2 symptoms (average score ≥3/ TSS≥15). Pts received PELA monotherapy 225 mg QD. The primary endpoint was complete hematologic response (CHR; normalization of platelet count (≤400 x 109/L), WBC count (≤10 x 109/L) confirmed after one cycle [after 3 weeks]) and normal spleen size. Secondary endpoints included partial HR (PHR; platelets 400–600 x 109/L and WBC ≤10 x 109/L), symptom improvement (≥50% TSS reduction) and safety. Results: As of July 2022, 20 pts with HR ET were treated: median age 64 yrs (42–83), median Hgb 13 (10–16) g/dL, median platelet count 772 (418–1255) x 109/L and median TSS 32.7 (6.9–123). The majority of pts had a hematologic response (90% [18/20] unconfirmed CHR or PHR); confirmed CHR was observed in 40% (8/20) (Table). Median platelet and WBC count at Wk 12 was 446 x109/L and 8.2 x 109/L, respectively. TSS reduction was reported in 86% (12/14 pts); median TSS reduction at Wk 12 was –31%. Hgb levels remained stable through Wk 24. The most common nonhematologic AEs were nausea (60%; 10% Gr 3), diarrhea (35%; 5% Gr 3) and dysgeusia (35%; no Gr 3). Hemorrhagic or thromboembolic events were reported in 30% pts (15% Gr 3). No events of thrombocytopenia and no Gr 4 events or higher were reported. Conclusions: Preliminary results from Arm 4 of the MANIFEST study suggest potential clinical benefit with PELA monotherapy in pts with HR ET refractory or intolerant to HU as supported by hematologic responses and symptom improvement. Safety results are consistent with the known safety profile of PELA and as expected in the underlying study population. Clinical trial information: NCT02158858 . [Table: see text]

Trifluridine/tipiracil (FTD/TPI) in extensively pre-treated metastatic colorectal cancer (mCRC) patients: Evaluation of prognostic subgroups of the TALLISUR study.

3556 Background: Compared to placebo, FTD/TPI significantly improved overall survival (OS) in patients (pts) with pre-treated mCRC in the pivotal phase III RECOURSE trial. Subgroup analyses indicated that all subgroups benefitted from FTD/TPI. Of note, FTD/TPI prolonged survival even more in pts ≥ 65 years old. To evaluate these observations with data from daily clinical practice, we performed a subgroup analysis of the TALLISUR study. Methods: In this prospective, multi-center, German, open-label, phase IV study, pts with extensively pre-treated mCRC chose between best supportive care (BSC) or oral FTD/TPI (35 mg/m2 bid on days 1 – 5 and 8 – 12 of each 28-day cycle). Duration of treatment and OS were analyzed for various subgroups. Based on a post-hoc analysis of the RECOURSE trial, 3 subgroups were defined according to: best, good and poor prognostic characteristics (BPC, GPC, PPC). Pts with < 3 metastatic sites at inclusion and ≥ 18 months from diagnosis to inclusion were considered to have GPC. GPC pts without liver metastasis at inclusion were considered to have BPC. All remaining pts were considered to have PPC. Results: Of 195 eligible pts, 186 pts chose treatment with FTD/TPI, while 9 pts decided to receive BSC only. Median OS was 6.9 (95% CI 6.1 – 8.3) months. Mean duration of treatment with FTD/TPI was 14.6 (range 0.1 – 102.7) weeks. Results of the subgroup analysis are summarized in the table. Pts ≥ 65 years old presented a longer median OS (7.2 vs 6.2 months). Conclusions: When given the choice between treatment and BSC in late-stage CRC, the vast majority of pts opted for treatment. Low metastatic burden and indolent disease were factors of good prognosis for FTD/TPI therapy regarding OS. Independent of baseline characteristics such as age, sidedness, and time of onset of metastases, virtually all pts benefitted from therapy with FTD/TPI. Albeit not statistically significant, elderly pts tend to have improved survival with FTD/TPI, consistent with results from RECOURSE. Clinical trial registration number: EudraCT No 2017-000292-83 . [Table: see text]

Invasive disease free survival and brain metastasis rates in patients treated with neoadjuvant chemotherapy with trastuzumab and pertuzumab.

589 Background: Patients (pts) with human epidermal growth factor receptor 2 (HER2) positive (+) early breast cancer (EBC) receiving neoadjuvant systemic therapy (NAST) have poorer outcomes if they have residual disease (RD) after surgery. HER2 negative (-) RD has been reported in 1/3 of pts after NAST. The KATHERINE trial suggests that pts with HER2- RD (8%) have better invasive disease-free survival (IDFS) with adjuvant (adj) trastuzumab emtansine (T-DM1) versus trastuzumab (H) alone. However, only 18% of the pts enrolled in the trial received NAST with trastuzumab and pertuzumab (HP). We aimed to analyze IDFS and brain metastasis (BM) rates in pts with HER2+ EBC in a modern population homogenously treated with NAST. We also report the incidence of pts with HER2- RD and their outcomes. Methods: Clinicopathologic data for pts with HER2+ EBC who received NAST between 1 Jan 2019 and 31 Jan 2022 were reviewed. External assessment of HER2 status before NAST was allowed. HER2 status of the surgical specimens with RD were assessed internally at our center. IDFS was defined as the time from surgery until first occurrence of invasive cancer recurrence, distant recurrence, or death from any cause. Results: The total cohort was 594 pts. 456 (77%) and 138 (23%) received antracycline-taxane and taxane based chemotherapy, respectively during NAST. 587 (99%) received HP and 7 (1%) received H alone. NAST was completed by 566 (95%) of pts. pCR (ypT0/isN0) was achieved in 325 (55%) and RD was seen in 269 (45%) pts. In 269 pts with RD, 46 (17%) did not have HER2 retesting and were excluded from the final analysis. In the remaining 223 pts, 143 (64%) were HER2+ and 80 (36%) were HER2-. In the 143 pts with HER2+ RD, adj TDM1, HP, H alone and no HER2 directed therapy were received by 120 (84%), 16 (11%), 1 (1%) and 6 (4%) of pts, respectively. In the 80 pts with HER2- RD, adj TDM1, HP, H alone and no HER2 directed therapy were received by 44 (55%), 27 (34%), 3 (4%) and 6 (7%) of pts, respectively. With a median follow up of 24 months, 7 pts developed BM at initial recurrence, 3/325 (0.9%) with pCR and 4/143 (2.8%) with HER2+ RD. None of the pts who developed BM had HER2- RD. IDFS events occurred in 22/594 (3%) pts. RD pts had a higher likelihood of having an IDFS event, 14/269 (5%) in RD and 8/325 (2%) in pCR (p = 0.04). In the evaluable 223 pts with RD there was no difference in IDFS between 10/143 (7%) pts with HER2+ RD or 4/80 (5%) with HER2- RD (p = 0.10). Conclusions: At a single center, in pts who predominantly received HP with chemotherapy as NAST, pts with RD had higher IDFS events than those with pCR. In those with RD, 36% lost HER2+ status; IDFS events appeared similar in those with HER2+ RD versus those with HER2- RD. The HER2 loss rate is higher than reported in KATHERINE possibly due to majority of pts receiving dual HP as NAST. The BM events seen in those with RD and pCR highlights the need for more effective therapy in NAST and adj setting to minimize BM risk.

Patterns of care delivery and outcomes in patients with melanoma brain metastases treated with ipilimumab/nivolumab.

e21510 Background: Patients (Pts) with metastatic melanoma presenting with brain metastases (MBM) have a high morbidity and mortality risk. The combination of ipilimumab/nivolumab (I/N) has demonstrated high intracranial response rates in selected, asymptomatic pts, suggesting there is a subset of pts who may be able to forgo or delay intracranial therapies. There is currently limited real world data on how many pts with MBM are successfully treated with this approach. We sought to explore our clinical experience at Duke University with combination immune checkpoint inhibitors for pts with MBM. Methods: An electronic database search was conducted for all metastatic melanoma pts treated with PD-1 therapies between 2015 and 2021. Pts treated with combination ICIs for brain metastases were included. The primary outcome was overall survival (OS). Secondary outcomes were need for local therapies (radiation (RT): stereotactic radiosurgery or whole brain radiation therapy or craniotomy), and immune related adverse events (irAEs). Results: Between 2015 and 2021, 66 pts with MBM received I/N, with a median follow-up of 30.4 months. Median age was 68, 60.6% were male and 61% had a BRAF mutation. 38 pts were asymptomatic. Of the 28 symptomatic patients 61% were on corticosteroids at the time of I/N initiation. 56% of pts received local therapy prior to start of I/N, 17% during and 18% after discontinuing I/N. 53% of pts were initiated on I/N as first line systemic therapy for MBM. 56% of patients had to discontinue I/N after one cycle because of high-grade irAEs. 13.8% of patients that received RT to the brain developed radionecrosis. Median OS was 25.6 months in the overall cohort, with a 1 year OS of 63%. There was a trend towards a higher risk of death for symptomatic versus asymptomatic patients HR:1.96 [95% CI: 0.96, 3.97; P:0.06]. Of the 38 asymptomatic patients, only 6 patients did not receive local therapies with either RT or craniotomy. Two of these patients died from melanoma progression, one from intra-cranial progression, the other from both intra-cranial and extra-cranial progression, and 4 remain alive without evidence of progression. Conclusions: The majority of pts with MBM are ultimately treated with multimodality therapy. Advances in systemic therapies have provided meaningful clinical benefit that could allow a limited number of asymptomatic patients to forgo local therapy, but currently few pts are treated in this manner.

Sintilimab, SBRT and GM-CSF for metastatic NSCLC: A prospective, multicenter, phase II trial.

e21172 Background: PD-1/PD-L1 inhibitors have transformed the therapeutic landscape in metastatic non-small cell lung cancer (NSCLC). However, the objective response rate (ORR) remains limited in unselected population. Incorporating SBRT to PD-1/PD-L1 inhibitors may improve treatment efficacy and the anti-tumor immunity induced by SBRT may be enhanced by GM-CSF, which plays a pivotal role in dendritic cell differentiation and maturation. The current trial (NCT04106180) is the first prospective, multicenter, phase II study assessing the safety and efficacy of a PD-1 inhibitor (Sintilimab), SBRT and GM-CSF in metastatic NSCLC patients without sensitizing driver mutations. Methods: Metastatic EGFR/ALK negative NSCLC pts who had failed first-line standard chemotherapy were eligible. Pts received SBRT (8 Gy*3) to one lesion, followed by Sintilimab (200 mg d1, every 3 weeks) and GM-CSF (125 μg/m2 d1-d14, cycle 1) within 3 weeks after SBRT. Sintilimab would be given continuously until disease progression, unacceptable toxicity, or up to 35 cycles. Primary end point is ORR. Secondary end points are safety, out-of-field response rate, overall survival (OS), progression free survival (PFS). The trial was designed to enroll 56 patients and if ≥17 pts evaluated had an objective response, it was regarded as positive. Results: By the time of 2022/10/30, the trial was early closed after 18 of the 51pts enrolled from 6 academic centers documented PR. The majority of pts were male, ECOG 1 and non-squamous NSCLC, having more than 5 lesions at baseline, with a median age of 62 (range, 32-74). The sites of SBRT included lung (n = 20), regional lymph node (n = 16), pleural nodule (n = 5), vertebra (n = 3), distant lymph node (n = 3), liver (n = 2) and others (n = 2). Treatment-related adverse event (TRAE) occurred in most pts and grade 3 TRAE occurred in 6 (11.8%) pts. No grade 4-5 TRAE occurred and the most common grade 3 TRAEs were ALT/AST elevation (n = 2), transient acute heart failure (recovered within 7 days) (n = 1), leucopenia/neutropenia (n = 2), pneumonitis (n = 1) and creatinine elevation (n = 1). With a median follow-up of 19.2 (range, 4.6-35.4) months, 49 pts had evaluable efficacy, with 18 PR, 15 SD and 16 PD. Median PFS and OS were 5.9 (95% CI, 3.9-9.2) and 16.2 (95% CI, 12.6-34.1) months, respectively. The results of biomarker testing will also be presented. Conclusions: Triple combination of Sintilimab, SBRT and GM-CSF is safe and shows promising efficacy in metastatic EGFR/ALK negative NSCLC. Clinical trial information: NCT04106180 .

Five-year survival outcomes in patients with melanoma with complete response to immunotherapy who discontinue therapy.

e21503 Background: Immune checkpoint inhibitor (ICI) therapy for advanced melanoma in the first-line setting often results in durable responses and prolonged overall survival (OS) after achieving a complete response (CR). While generally well-tolerated, there are financial toxicities and treatment related adverse events (TRAEs) associated with ICI use. There are limited data to inform the optimal duration of therapy after CR, and how specific patient factors may lead to variable OS in patients (pts) with CR. Methods: Pts with locally advanced stage III or stage IV melanoma who started first-line ICI therapy with pembrolizumab, nivolumab, or ipilimumab/nivolumab (ipi/nivo) and achieved CR were identified at a single institution under an Institutional Review Board approved protocol. Pts were only included in the sample if they had initiated treatment by 2013 and discontinued therapy by February of 2021 and had documented follow-up at least 1 year after discontinuing ICI therapy. Recurrence rates were determined by the presence of any recurrence after CR. Pts were analyzed by baseline stage (III vs IV), BRAF status, use of steroids for TRAEs, time from treatment start to CR, and total duration of therapy. OS was determined by time from treatment start to death or date of last follow-up. Results: 78 Pts with CRs from ICI therapy who discontinued treatment were identified at the University of Pennsylvania. Median follow-up time was 63 months from ICI treatment start. Median age at treatment start was 65 years (range 33-94). 51 Pts (68%) had an ECOG performance status (PS) of 0 vs 24 (32%) with ECOG PS of 1-2. 21 Pts (27%) had locally advanced stage III and 57 (73%) had stage IV disease. Of stage IV pts, 8 were M1a, 16 M1b, 22 M1c, and 11 M1d. 61 (78%) pts were treated with pembrolizumab, 5 (6%) nivolumab, 12 (15%) ipi/nivo. 34 pts (44%) were treated with steroids for TRAEs. Of the 78 total pts, 13 (16.7%) developed a recurrence after stopping treatment. The median time to recurrence was 57 months (range 9-110). Melanoma specific survival was 96%. Of the pts with recurrence, 3 died of melanoma, 9 are disease free after additional local and/or systemic treatment and one patient is alive with disease. There was no significant difference ( p < 0.05) in OS based on baseline stage, BRAF status, or use of steroids for TRAEs. Pts were treated for a median of 6 months (range 1 day to 24 months). Conclusions: With over 5 years median follow-up time, the majority of pts with advanced melanoma who attain a CR from first-line ICI therapy remain disease free after treatment discontinuation. Patient factors including stage at treatment initiation, BRAF status, and steroid usage during treatment were not associated with significant variation in OS in this cohort. Most pts with recurrences remain disease free after additional local and/or systemic treatment. Few melanoma specific deaths occurred in pts with a CR to ICI who discontinued treatment.