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PURPOSE In patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. In the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable modeled cancer antigen-125 [CA-125] ELIMination rate constant K [KELIM] score) was a predictive biomarker. Only the patients with high-risk disease (suboptimally resected stage III, or stage IV) exhibiting unfavorable KELIM score < 1.0 had overall survival (OS) benefit from bevacizumab (median: 29.7 v 20.6 months; hazard ratio [HR], 0.78). An external validation study in the GOG-0218 trial was performed. METHODS In GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel ± concurrent-maintenance bevacizumab/placebo. Patient KELIM values were calculated with CA-125 kinetics during the first 100 chemotherapy days by the Lyon University team. The association between KELIM score (favorable ≥ 1.0, or unfavorable < 1.0) and bevacizumab benefit for progression-free survival (PFS)/OS was independently assessed by NGR-GOG using univariate/multivariate analyses. RESULTS KELIM was assessable in 1,662 patients with ≥ 3 CA-125 available values. An unfavorable KELIM score was associated with bevacizumab benefit compared with placebo (PFS: HR, 0.70; 95% CI, 0.59 to 0.82; OS: HR, 0.87; 95% CI, 0.73 to 1.03), whereas a favorable KELIM was not (PFS: HR, 0.96; 95% CI, 0.79 to 1.17; OS: HR, 1.11; 95% CI, 0.89 to 1.39). The highest benefit was observed in patients with a high-risk disease exhibiting unfavorable KELIM, for PFS (median: 9.1 v 5.6 months; HR, 0.64; 95% CI, 0.53 to 0.78), and for OS (median: 35.1 v 29.1 months; HR, 0.79; 95% CI, 0.65 to 0.97). CONCLUSION This GOG-0218 trial investigation validates ICON-7 findings about the association between poor tumor chemosensitivity and benefit from concurrent-maintenance bevacizumab, suggesting that bevacizumab may mainly be effective in patients with poorly chemosensitive disease. Bevacizumab may be prioritized in patients with a high-risk and poorly chemosensitive disease to improve their PFS/OS (patient KELIM score calculator available on the Biomarker Kinetics website).

Background and Aims Combination atezolizumab/bevacizumab is the gold standard for first-line treatment of unresectable hepatocellular carcinoma (HCC). Our study investigated the efficacy and safety of combination therapy in older patients with HCC. Methods 191 consecutive patients from eight centres receiving atezolizumab and bevacizumab were included. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in older (age ≥ 65 years) and younger (age

Background Atezolizumab plus bevacizumab (Atezo/Bev) is first line-treatment for unresectable hepatocellular carcinoma (HCC). Body mass index (BMI) has demonstrated predictive value for response to immunotherapy in non-HCC cancer types. Our study investigated the effect of BMI on safety and efficacy of real-life use of Atezo/Bev for unresectable HCC. Methods 191 consecutive patients from seven centres receiving Atezo/Bev were included in the retrospective study. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in overweight (BMI ≥ 25) and non-overweight (BMI Results Patients in the overweight cohort (n = 94) had higher rates of non-alcoholic fatty liver disease (NAFLD) and lower rates of Hepatitis B compared to non-overweight cohort (n = 97). Baseline Child–Pugh class and Barcelona Clinic Liver Cancer stage were similar between cohorts, with lower rates of extrahepatic spread in the overweight group. Overweight patients had similar OS compared to non-overweight (median OS 15.1 vs. 14.9 months; p = 0.99). BMI did not influence median PFS (7.1 vs. 6.1 months; p = 0.42), ORR (27.2% vs. 22.0%; p = 0.44) and DCR (74.1% vs. 71.9%; p = 0.46). There were higher rates of atezolizumab-related fatigue (22.3% vs. 10.3%; p = 0.02) and bevacizumab-related thrombosis (8.5% vs. 2.1%; p = 0.045) in the overweight patients, but overall trAEs and treatment discontinuation were comparable between cohorts. Conclusion Atezo/Bev has comparable efficacy in overweight HCC patients, with an increase in treatment-related fatigue and thrombosis. Combination therapy is safe and efficacious to use in overweight patients, including those with underlying NAFLD.

Atezolizumab plus bevacizumab (AtezoBev) is the standard of care for first-line treatment of unresectable HCC. No evidence exists as to its use in routine clinical practice in patients with impaired liver function.In 216 patients with HCC who were consecutively treated with AtezoBev across 11 tertiary centers, we retrospectively evaluated treatment-related adverse events (trAEs) graded (G) according to Common Terminology Criteria for Adverse Events v5.0, including in the analysis all patients treated according to label (n = 202, 94%). We also assessed overall survival (OS), progression-free survival (PFS), overall response (ORR), and disease control rates (DCR) defined by Response Evaluation Criteria in Solid Tumors v1.1. Disease was mostly secondary to viral hepatitis, namely hepatitis C (n = 72; 36%) and hepatitis B infection (n = 35, 17%). Liver function was graded as Child-Pugh (CP)-A in 154 patients (76%) and CP-B in 48 (24%). Any grade trAEs were reported by 143 patients (71%), of which 53 (26%) were G3 and 3 (2%) G4. Compared with CP-A, patients with CP-B showed comparable rates of trAEs. Presence and grade of varices at pretreatment esophagogastroduodenoscopy did not correlate with bleeding events. After a median follow-up of 9.0 months (95% CI, 7.8-10.1), median OS was 14.9 months (95% CI, 13.6-16.3), whereas median PFS was 6.8 months (95% CI, 5.2-8.5). ORR and DCR were respectively 25% and 73%, with no difference across CP classes.This study confirms reproducible safety and efficacy of AtezoBev in routine practice. Patients with CP-B reported similar tolerability compared with CP-A, warranting prospective evaluation of AtezoBev in this treatment-deprived population.

Different approaches are available after progression of disease (PD) to immune checkpoint inhibitors (ICI) for hepatocellular carcinoma (HCC), including continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiologic patterns of progression and survival post-ICI, also appraising treatment strategies.We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut-off. We evaluated post-progression survival (PPS) according to treatment strategy at PD and verified its relationship with radiologic patterns of progression: intrahepatic growth (IHG), new intrahepatic lesion (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH) and new vascular invasion (nVI).Of 604 patients, 364 (60.3%) experienced PD during observation. Median PPS was 5.3 months (95%CI: 4.4-6.9; 271 events). At data cut-off, 165 patients (45%) received no post-progression anticancer therapy; 64 patients (17.6%) continued ICI beyond PD. IHG (HR 1.64 [95%CI:1.21-2.22]; p=0.0013) and nVI (HR 2.15 [95%CI:1.38-3.35]; p=0.0007) were associated with shorter PPS. Multivariate models adjusted for progression patterns, treatment line, and ALBI grade and ECOG-PS at PD confirmed receipt of ICI beyond PD with (HR 0.17, 95%CI 0.09-0.32; p0.0001), or without subsequent TKI (HR 0.39, 95%CI 0.26-0.58; p0.0001) as predictors of prolonged PPS versus no anticancer therapy.ICI-TKI sequencing is a consolidated option in advanced HCC. nVI and IHG predict poorer prognosis. Despite lack of recommendation, continuation of ICI beyond progression in HCC is adopted clinically: future efforts should appraise which patients benefit from this approach.

Simple Summary The investigation of predictive and prognostic markers is pivotal in patients affected by hepatocellular carcinoma treated with immune-checkpoint-inhibitors. Inflammation has a central role in hepatocellular carcinoma development and progression; however, its role in influencing outcomes in the context of immunotherapy has not been fully elucidated yet. In the following study, we investigated the prognostic role of bloods derived inflammatory markers and we found that they predict survival and response of patients treated with immunotherapy for advanced hepatocellular carcinoma. Abstract Systemic inflammation is a hallmark of cancer, and it has a pivotal role in hepatocellular carcinoma (HCC) development and progression. We conducted a retrospective study including 362 patients receiving immune check-point inhibitors (ICIs) across three continents, evaluating the influence of neutrophiles to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), and prognostic nutritional index (PNI) on overall (OS), progression free survival (PFS), and radiologic responses. In our 362 patients treated with immunotherapy, median OS and PFS were 9 and 3.5 months, respectively. Amongst tested inflammatory biomarkers, patients with NLR ≥ 5 had shorter OS (7.7 vs. 17.6 months, p < 0.0001), PFS (2.1 vs. 3.8 months, p = 0.025), and lower objective response rate (ORR) (12% vs. 22%, p = 0.034); similarly, patients with PLR ≥ 300 reported shorter OS (6.4 vs. 16.5 months, p < 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). NLR emerged as independent prognostic factors for OS in univariate and multivariate analysis (HR 1.95, 95%CI 1.45–2.64, p < 0.001; HR 1.73, 95%CI 1.23–2.42, p = 0.002) and PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, 95%CI 1.6–2.40, p = 0.020; HR 1.99, 95%CI 1.11–3.49, p = 0.021). Systemic inflammation measured by NLR and PLR is an independent negative prognostic factor in HCC patients undergoing ICI therapy. Further studies are required to understand the biological mechanisms underlying this association and to investigate the predictive significance of circulating inflammatory biomarkers in HCC patients treated with ICIs.

Background and Rationale: Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC. Methods: In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within −30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. Results: Our study comprised mostly cirrhotic (329, 73.3%) males (355, 79.1%) with a Child-Turcotte Pugh class of A (332, 73.9%), receiving ICI after 1 therapy line (251, 55.9%) for HCC of Barcelona clinic liver cancer stage C (325, 72.4%). EIOP (n = 170, 37.9%) was independent of baseline clinicopathologic features of HCC and correlated with longer PFS (6.1 vs. 3.7 months, log-rank p = 0.0135). EIOP+ patients had similar OS, overall response, and disease control rates (DCRs) compared to EIOP. The effect of EIOP persisted in landmark time analyses and in multivariable models, confirming the independent predictive role of EIOP in influencing PFS following adjustment for covariates reflective of tumor burden, liver function, and ICI regimen administered. In patients receiving programmed cell death-1 receptor/ligand inhibitors monotherapy, EIOP was also associated with higher DCRs (61.4% vs. 50.9%, p = 0.0494). Conclusions: Unlike other oncological indications, ATB in the 30 days before or after ICI initiation is associated with improved benefit from immunotherapy, independent of disease and treatment-related features. Evaluation of the immune microbiologic determinants of response to ICI in HCC warrants further investigation.

Background: The Oncotype DX Recurrence Score (RS) predicts recurrence and chemotherapy benefit in early stage estrogen receptor positive breast cancer patients. Cost and unavailability are two major disadvantages of the assay. Multiple models have been developed to predict the RS using different pathobiologic parameters. The goal of our study was to predict RS based on histopathologic and biomarker features, and to determine concordance and correlation with RS of three surrogate models that are independent of Ki67 index: Breast Cancer Prognostic Score (BCPS), Magee0, and Magee2. Methods: Early stage, ER-positive breast cancer cases with available RS were reviewed (n = 442). ER, PR and HER2 subscores were abstracted from the Oncotype DX reports. RS categories were stratified by pathologic and biomarker variables. Histopathologic and biomarker data were abstracted from pathology reports, and the surrogate RS was calculated by each model. Correlation and concordance between models and actual RS were calculated. Analyses were performed using both conventional (18, 30) and TAILORx (11, 25) thresholds. Results: Less than 5% of breast cancers with pure or mixed lobular features, low grade tumors, carcinomas with high PR content, or Luminal A tumors had a RS >25 (Table 1). Recurrence scores in node-positive tumors were not significantly higher compared to node-negative cases. Both actual and calculated RS were higher in Luminal B versus Luminal A breast cancers. Subscore analysis revealed 99.5% concordance for ER status, 90% concordance for PR status, and 96% concordance for HER2 status (Table 2). BCPS, Magee0, and Magee2 algorithms demonstrated correlation coefficients with RS of 0.63, 0.61, and 0.62, respectively. BCPS showed the best agreement with RS using conventional cutoffs (73%), whereas the two Magee algorithms showed better concordance with the TAILORx thresholds. Two-step discordances were uncommon, especially with the TAILORx cutoffs and Magee2. When a RS of 25 was used to separate high risk from non-high risk cases, concordance rates of 86-88% were achieved for all three models. Using different tumor blocks for Oncotype and biomarker testing did not adversely affect correlation or concordance with RS. Discussion: High RS was observed only in a small percentage of pure or mixed lobular carcinomas, low grade or Luminal A tumors, and tumors with high PR expression, suggesting that these breast cancers may not require Oncotype testing. All three surrogate models demonstrated comparable correlation and high concordance with the RS when a cutoff of 25 was used, suggesting their utility in cases where the actual RS in unavailable. Our data also indicate that models using different hormone receptor quantitation methods (Allred versus H-score) have similar performance characteristics. Possible sources of discordance between actual and computed RS include methodological differences, variable tumor cellularity, intratumoral heterogeneity, and inflammatory infiltrates. Table 1.Stratification of RS Risk Categories by Pathologic and Biomarker VariablesConventional Risk CategoryLow RiskIntermediate RiskHigh RiskTAILORx Risk CategoryLow RiskIntermediate RiskHigh RiskOncotype DX Recurrence Score30n (%)n (%)n (%)n (%)n (%)Histologic Type (n)Invasive ductal carcinoma (340)94 (28)121 (36)73 (21)20 (6)32 (9)Invasive lobular carcinoma (47)10 (21)27 (57)8 (17)1 (2)1 (2)Mixed ductal/lobular carcinoma (22)3 (14)15 (68)4 (18)0 (0)0 (0)Invasive mucinous carcinoma (10)4 (40)4 (40)0 (0)1 (10)1 (10)Molecular Subtype (n)Luminal A (317)112 (35)143 (45)46 (15)11 (3)5 (1)Luminal B (125)9 (7)33 (26)41 (33)10 (8)32 (26)Combined Tumor Grade (n)Low (143)45 (31)59 (41)32 (22)4 (3)3 (2)Intermediate (239)69 (29)101 (42)41 (17)13 (5)15 (6)High (60)5 (8)17 (28)13 (22)5 (8)20 (33)ER (n)High (Allred Score 7-8) (408)120 (29)164 (40)74 (18)21 (5)29 (7)High (Modified H Score ≥ 200) (320)101 (32)133 (42)54 (17)15 (5)17 (5)Low (Allred Score 3-6) (34)1 (3)12 (35)12 (35)1 (3)8 (24)Low (Modified H Score < 200) (122)18 (15)45 (37)33 (27)7 (6)19 (16)PR (n)High (Allred Score 7-8) (306)106 (35)146 (48)41 (13)9 (3)4 (2)High (Modified H Score ≥ 200) (248)96 (39)111 (45)31 (13)8 (3)2 (1)Low (Allred Score 3-6) (97)12 (12)27 (28)32 (33)7 (7)19 (20)Low (Modified H Score 1-199) (155)23 (15)61 (39)41 (26)9 (6)21 (14)Negative (Allred Score 0-2) (39)1 (3)5 (13)14 (36)5 (13)14 (36)Negative (Modified H Score Table 2.Concordance Between Clinical ER, PR, and HER2 Status and Oncotype DX SubscoreOncotype DX SubscoresClinical LabNegativeBorderlinePositiveERNegative0N/A0Positive2N/A379PRNegative29N/A4Positive34N/A314HER2Negative36540Equivocal800Positive220 Citation Format: Joseph Geradts, Aisha Kousar, Jan Wong, Nasreen Vohra, Mahvish Muzaffar, Anas Mohamed. Prediction of oncotype DX recurrence score by patho-biologic variables and three surrogate models [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-06-09.

Immune checkpoint inhibitors (ICIs) are a breakthrough in therapy for many solid malignancies. ICIs suppress the inhibitory signaling of several immune cell subtypes by the blocking the ligation of...

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized treatment of advanced hepatocellular carcinoma. Integrated use of transarterial chemoembolization (TACE), a locoregional inducer of immunogenic cell death, with ICI has not been formally assessed for safety and efficacy outcomes.MethodsFrom a retrospective multicenter dataset of 323 patients treated with ICI, we identified 31 patients who underwent >1 TACE 60 days before or concurrently, with nivolumab at a single center. We derived a propensity score-matched cohort of 104 patients based on Child-Pugh Score, portal vein thrombosis, extrahepatic metastasis and alpha fetoprotein (AFP) who received nivolumab monotherapy. We described overall survival (OS), progression-free survival (PFS), objective responses according to modified RECIST criteria and safety in the multimodal arm in comparison to monotherapy.ResultsOver a median follow-up of 9.3 (IQR 4.0–16.4) months, patients undergoing multimodal immunotherapy with TACE achieved a significantly longer median (95% CI) PFS of 8.8 (6.2–23.2) vs 3.7 (2.7–5.4) months (log-rank 0.15, pConclusionsTACE can be safely integrated with programmed cell death 1 blockade and may lead to a significant delay in tumor progression and disease downstaging in selected patients.

Objective To evaluate the antibody-drug conjugate- sacituzumab govitecan, its pharmacological properties, toxicity, data supporting efficacy against a wide variety of solid tumors beyond breast cancer, and potential future uses. Data Sources Articles in MEDLINE/PubMed databases and the National Institutes of Health Clinical Trials Registry ( http://www . clinicaltrials.gov) between January 1, 2015, and July 1, 2021 using MeSH terms sacituzumab govitecan(- hziy) and solid tumors were reviewed. Data Summary Antibody-drug conjugates (ADC's) are a subclass of emerging cancer therapeutics which combines chemotherapy with targeted antibodies. Sacituzumab govitecan (SG) is a novel antibody drug conjugate that has recently been approved by the Food and Drug Administration (FDA) in adult patients for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. The approval of sacituzumab govitecan provides a new option for solid tumors that need to be further explored. In this review article, we discussed the pharmacokinetics, pharmacodynamics, safety profile of sacituzumab govitecan and various ongoing clinical trials on sacituzumab govitecan. Conclusion Sacituzumab is a significant advancement made in cancer therapy. SG has showed significantly improved Health-related quality of life (HRQoL) in addition to prolonged progression free survival and Over all survival in addition to maintaining a good safety profile. Multiple clinical trials on SG are ongoing to evaluate the potential use of SG as neoadjuvant therapy in triple negative breast cancer, as an Adjuvant therapy, in combination with immunotherapy, and also for various solid tumors.

Background: Reduction in breast density may be a biomarker of endocrine therapy (ET) efficacy. Our objective was to assess the impact of race on ET-related changes in volumetric breast density (VBD). Methods: This retrospective cohort study assessed longitudinal changes in VBD measures in women with estrogen receptor–positive invasive breast cancer treated with ET. VBD, the ratio of fibroglandular volume (FGV) to breast volume (BV), was measured using Volpara software. Changes in measurements were evaluated using a multivariable linear mixed effects model. Results: Compared with white women (n = 191), black women (n = 107) had higher rates of obesity [mean ± SD body mass index (BMI) 34.5 ± 9.1 kg/m2 vs. 30.6 ± 7.0 kg/m2, P < 0.001] and premenopausal status (32.7% vs. 16.7%, P = 0.002). Age- and BMI-adjusted baseline FGV, BV, and VBD were similar between groups. Modeled longitudinal changes were also similar: During a follow-up of 30.7 ± 15.0 months (mean ± SD), FGV decreased over time in premenopausal women (slope = −0.323 cm3; SE = 0.093; P = 0.001), BV increased overall (slope = 2.475 cm3; SE = 0.483; P < 0.0001), and VBD decreased (premenopausal slope = −0.063%, SE = 0.011; postmenopausal slope = −0.016%, SE = 0.004; P < 0.0001). Race was not significantly associated with these longitudinal changes, nor did race modify the effect of time on these changes. Higher BMI was associated with lower baseline VBD (P < 0.0001). Among premenopausal women, VBD declined more steeply for women with lower BMI (time × BMI, P = 0.0098). Conclusions: Race does not appear to impact ET-related longitudinal changes in VBD. Impact: Racial disparities in estrogen receptor–positive breast cancer recurrence and mortality may not be explained by differential declines in breast density due to ET.

Introduction: Immunotherapy has improved outcomes in patients with advanced stage lung cancer. However, the studies which led to approval of these therapies did not include a substantial number of Black patients. Studies focusing on racial disparities in advanced stage non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) report conflicting data. In an equal access setting, some studies have demonstrated improved outcomes in Black patients. Very few studies have high or equal representation of Black patients, and these studies lack detail on access to care, such as time to treatment initiation (TTI) in this target population. To our knowledge, this study is one of few with almost equal representation of Black and White patients. Methods: This was an IRB approved retrospective study of stage IV NSCLC patients > 18 years who received immunotherapy-based systemic therapy at Vidant Medical Center between 2014 and 2021. Analyses were done utilizing IBM PSAW (SPSS Version 28). Associations between race and other demographic characteristics were examined using chi-square tests. Kaplan-Meier curves were generated to determine overall survival (OS) and progression-free survival (PFS) stratified by race. Multivariate Cox proportional hazards model was applied to determine predictors of OS and PFS. A p-value < 0.05 was deemed statistically significant. Results: Of 194 patients who met the eligibility criteria, 42.3% were Black (n=82). On Kaplan-Meier analysis, there was no difference in median PFS (6.30 versus 7.90 months; log-rank p=0.977) and OS (9.50 versus 11.77 months; log-rank p=0.457) between White and Black patients respectively. On multivariate analysis, there was no difference in PFS (HR: 0.98; 95% CI: 0.68,1.43; p=0.928) or OS (HR: 1.01; 95% CI: 0.67,1.51; p=0.969) when controlling for race, sex, age at diagnosis, pack years, marital status, insurance type, histology, and Charlson Comorbidity Index (CCI). The most frequently administered ICIs were pembrolizumab (74.7%), nivolumab (13.4%), atezolizumab (8.8%), nivolumab plus ipilimumab (1.5%), and durvalumab (1.5%). There was no difference in treatment selection between Black and White patients (p=0.184; chi-square). Median time to initial overall cancer treatment initiation (28.00 days versus 22.00 days; p=0.159) did not differ, but there was a significant difference in median time to immunotherapy initiation (34.00 versus 27.00 days; p=0.042) between White and Black patients respectively. Conclusion: Although race was expected to permeate patient outcomes, OS and PFS did not differ between Black and White patients. The significantly shorter time to immunotherapy treatment for Black patients is an unexpected finding. In our study we highlighted that equitable access reduces disparities, bridges gaps in care, and improves patient outcomes, regardless of race. Further studies with equitable representation of diverse racial groups are warranted to better understand how race impacts cancer outcomes. Citation Format: Melisa Pasli, Radhamani Kannaiyan, Praveen Namireddy, Mahvish Muzaffar. Impact of race on the outcomes of advanced stage non-small cell lung cancer in an equal access setting [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B127.

The availability of immune checkpoint inhibitors (ICIs) for the management of advanced hepatocellular cancer (HCC) has changed the treatment paradigm. There are emerging questions regarding the efficacy of subsequent anticancer therapies. The primary aim of this retrospective, multicenter study was to examine the types of anticancer treatment received after ICIs and to assess the impact on post-ICI survival. We established an international consortium of 11 tertiary-care referral centers located in the USA (n = 249), Europe (n = 74), and Asia (n = 97), and described patterns of care following ICI therapy. The impact of subsequent therapy on overall survival (OS) was estimated using the Kaplan–Meier method and presented with a 95% confidence interval (CI). A total of 420 patients were treated with ICIs for advanced HCC after one line of systemic therapy (n = 371, 88.8%): 31 (8.8%) had died, 152 (36.2%) received best supportive care (BSC) following ICIs, and 163 patients (38.8%) received subsequent anticancer therapy. Tyrosine kinase inhibitors (TKIs, n = 132, 80.9%), in particular sorafenib (n = 49, 30.0%), were the most common post-ICI therapy followed by external beam radiotherapy (n = 28, 17.2%), further immunotherapy (n = 21, 12.9%), locoregional therapy (n = 23, 14.1%), chemotherapy (n = 9, 5.5%), and surgery (n = 6, 3.6%). Receipt of post-ICI therapy was associated with longer median OS compared with those who had received BSC (12.1 vs. 3.3 months; hazard ratio [HR]: 0.4 (95% CI: 2.7–5.0). No difference in OS was noted in those patients who received TKI before ICIs compared with those who received ICIs followed by TKI. Conclusion: Post-ICI therapy is associated with OS in excess of 12 months, suggesting a role for therapeutic sequencing. OS from TKI therapy was similar to that reported in registration studies, suggesting preserved efficacy following ICIs.

Context.— The Oncotype DX Recurrence Score (RS) predicts recurrence and chemotherapy benefit in early-stage estrogen receptor–positive breast cancer patients. Cost and unavailability are 2 major disadvantages of the assay. Multiple models have been developed to predict the RS. Objective.— To predict RS based on histopathologic and biomarker features, and to measure concordance and correlation with RS of the following 3 algorithms: breast cancer prognostic score, Magee0, and Magee2. Design.— Breast cancer cases with available RSs were reviewed (n = 442). RS categories were stratified by pathologic and biomarker variables. Histopathologic and biomarker data were abstracted from pathology reports, and RS was calculated by each model. Correlation and concordance between models and RS were calculated. Results.— Less than 5% of breast cancers with lobular features, low-grade tumors, carcinomas with high progesterone receptor content, or luminal A tumors had an RS greater than 25. Breast cancer prognostic score, Magee0, and Magee2 demonstrated correlation coefficients with RS of 0.63, 0.61, and 0.62, respectively. Two-step discordances were uncommon. When an RS of 25 was used to separate high-risk from non–high-risk cases, concordance rates of 86% to 88% were achieved. Conclusions.— High RS was observed only in a small percentage of pure or mixed lobular carcinomas, low-grade or luminal A tumors, and tumors with high progesterone receptor expression, suggesting that these cancers may not require Oncotype testing. All 3 surrogate models demonstrated comparable correlation and high concordance with the RS when a cutoff of 25 was used, suggesting their utility in cases where the actual RS is unavailable.

Purpose The development of treatment-related adverse events (trAE) correlates favorably with clinical outcomes in multiple studies of patients receiving immune checkpoint inhibitors (ICI); however, this relationship is undefined in patients with hepatocellular carcinoma (HCC). Patients and methods We derived a cohort of 406 patients with unresectable/advanced HCC receiving ICI therapy as part of international clinical trials submitted to the US Food and Drug Administration (FDA) in support of marketing applications. We tested whether the development of clinically significant trAE (i.e. graded ≥2, trAE2) predicted improved overall survival (OS), progression-free survival (PFS), and objective response rates (ORR) following ICI. We established an international consortium of 10 tertiary-care referral centres located in Europe (n = 67), United States (US, n = 248) and Asia (n = 42) to validate this association. Results In the FDA dataset of 406 patients, 325 (80%) with Barcelona Clinic Liver Cancer (BCLC) stage C HCC mostly treated with ICI monotherapy (n = 258, 64%), trAE2 were reported in 228 patients (56.1%). Development of trAE2 was associated with longer OS (16.7 versus 11.2 months) and PFS (5.5 versus 2.2 months) and persisted as an independent predictor of outcome after adjusting for viral aetiology, gender, Child-Pugh class, BCLC stage, AFP levels, ECOG-PS, ICI regimen (mono/combination therapy) and receipt of corticosteroid therapy. In a multi-institutional cohort of 357 patients with similar characteristics mostly treated with ICI monotherapy (n = 304, 85%), the development of trAE2 was associated with longer OS (23.3 versus 12.1 months) and PFS (9.6 versus 3.9 months). TrAE2 were confirmed predictors of improved OS (HR 0.43; 95% CI:0.25–0.75) and PFS (HR 0.48; 95% CI: 0.31–0.75), with multivariable analyses confirming their association with outcome independent of clinicopathologic features of interest. Additional time-varying multivariable analyses also indicated that trAEs were associated with a decreased risk of progression (HR 0.56, 95% CI: 0.46–0.67) in the FDA dataset and death (HR 0.55; 95% CI: 0.32–0.95) in the multi-institutional dataset. Conclusion Development of trAE2 correlates with improved outcomes in patients with HCC receiving ICI in clinical trials and in routine practice. Prospective studies aimed at understanding the underlying immunologic foundations of such relationships are warranted to identify predictive biomarkers of toxicity and response.

Background: The risk of breast cancer increases with advancing age. Routine use of screening mammogram in women after 75yrs and its impact on overall survival is controversial. Studies have also found that elderly breast cancer patients are underrepresented among clinical trials and a tendency for undertreatment may result in inferior outcome. Method and Material:Female patients with breast cancer who were 75 years or older and diagnosed from 2000-2015 were identified from Surveillance, Epidemiology, and End Results (SEER) 18 database. We excluded patients with unknown stage and race. We performed multivariate and survival analysis using JMP pro 13. Results: 186,682 women with breast cancer of ≥ 75 yrs. were identified from the SEER. 167,802 patients met the inclusion criteria. Mean age was 81.27 years (CI 95% 81.25-81.30). Most of the patients were white (88%), and had Stage I/II (83%) breast cancer.78% of patients had estrogen receptor positive cancer, while 66% had grade 1/2 disease. The 5-year overall survival was 74% for Stage I,60% for Stage II,38% for stage III and 11% for Stage IV cancer(p Cox proportional hazards regression model of overall survivalVariableHazard ratio( 95% CI)p value75—79 80-84 85+1 1.22 1.7 Conclusion: Early breast cancer continues to be the most common presentation for patients ≥75 yrs. of age. Historical prognostic factors of breast cancer like race, hormone receptor status, stage and grade continue to impact cancer outcome among elderly patients. Only 24% of deaths among the deceased were attributed to this breast cancer highlighting the concern for over diagnosis. Nonetheless once diagnoses is established a multidisciplinary comprehensive geriatric assessment should be the cornerstone of the management. Citation Format: Muzaffar M, Vohra N, Wong J. Breast cancer in elderly women: Ageism or primum non nocere? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-06.

e21050 Background: Programmed death ligand-1 (PD-L1) expression is predictive of immunotherapy benefit. However, tissue PD-L1 protein immunohistochemical testing can be fraught with tissue acquisition and heterogeneity limitations. PD-L1 expression by RNA sequencing can be performed by both tissue and plasma with tissue PD-L1 protein correlations. What has not been well characterized is the correlation of plasma cell free circulating tumor RNA (cfRNA) PD-L1 and clinical outcomes with immunotherapy. Plasma cfRNA PD-L1 expression was evaluated and correlated with immunotherapy benefit in advanced non-small cell lung cancers (NSCLC). Methods: Patients with advanced NSCLC undergoing plasma next-generation sequencing including plasma cfRNA.PD-L1 testing in a Clinical Laboratory Improvement Amendments (CLIA) and College of American pathologists (CAP) accredited laboratory were retrospectively identified and evaluated at a single institution. Plasma PD-L1 positive patients underwent a de-identified chart abstraction to identify those patients with advanced NSCLC treated with front line immunotherapy regimens and those who received cytotoxic chemotherapy alone. Results: Sixteen patients with plasma PD-L1 expression treated with front-line immunotherapy regimens including single-agent immune checkpoint inhibitors, and combinatorial chemo-immune or chemo-immune-bevacizumab regimens were assessed for overall survival (OS). Eleven patients with plasma PD-L1 expression who received chemotherapy were used as a non-immunotherapy OS comparison. Median OS for the immunotherapy treated patients was thirteen months with a thirty percent three year landmark OS versus four months median OS and a ten percent three-year landmark OS for those treated with chemotherapy alone. Comparative log-rank test p-value 0.0091 and a hazard ratio of 0.36 (95%-CI 0.13-0.99). Conclusions: Plasma cfRNA PD-L1 expression is predictive of a statistically significant survival benefit from immunotherapy treatment compared to chemotherapy in the first line treatment of advanced NSCLC. The three year landmark OS of thirty percent parallels tissue PD-L1 directed immunotherapy-based treatment outcomes. The clinical utility of plasma cfRNA PD-L1 to overcome tissue acquisition and PD-L1 protein heterogeneity limitations and to study the dynamic nature of PD-L1 expression with non-immune cancer treatments and potential immunotherapy response monitoring are undergoing ongoing research.

e21047 Background: There has been prospective and retrospective evidence for the onset of immunotherapy (IO) related adverse events (irAE) and efficacy of anti programmed death (PD1) and Programmed death Ligand 1(PD L1) antibodies. The incidence of irAE in these studies ranged anywhere from 30-44%. There have been attempts in the past to cluster irAEs into distinct subtypes by T cell profiling before and after immunotherapy. Identifying the trend of CD4/CD8 changes during irAE may aid in finding ways to mitigate the severe toxicities, so the benefits of immunotherapy can be extended to far more number of patients. Methods: We have collected blood samples from 20 patients of Non Small Cell Lung Cancer patients (NSCLC) before each cycle of immunotherapy with informed consent. We have measured the different inflammatory markers such as IL6, IL10 using ELISA and isolated cellular components such as CD4, CD8 T cells along with others using magnetic bead technique, from these samples in our research laboratory at East Carolina University. We have also collected clinical information including the adverse events with their (Common Terminology Criteria for Adverse events) CTCAE 5.0 grading, different cell counts and C- reactive Protein (CRP). Results: In the cohort of 20 patients, 9 experienced irAE, out of which 6 had grade 2, including thyroiditis, pneumonitis, dermatitis, cytokine release syndrome (CRS), 1 had grade 3 pneumonitis, 1 had grade 4 pneumonitis and 1 had grade 1 CRS. When we looked at the CD4/CD8 ratio before each cycle, the one prior to the incidence of the irAE had at least 30-40% drop in the ratio consistently although there were minor fluctuations in the ratio at other times in both directions. Conclusions: Although most irAEs can be treated and reversed with steroids and other immunosuppressive agents, prolonged immunosuppression can lead to reduced efficacy of IO and development of undue opportunistic infections. Experience with IO has shown that earlier initiation of immunosuppression shortens the required treatment. However, given the challenge in the subtility of the earlier presentation, therapies are frequently delayed. Hence, biomarker to identify the early manifestations is of critical importance for early intervention. Studies suggest there is clonal expansion of CD8 T cells preceding grade 2-3 irAEs. Studies also indicate that increased T cells in the tumor is indicative of response to immunotherapy. Our observation suggests that increased CD8 in proportion to CD4 in the peripheral blood precedes the onset of irAE. It is unclear as to how this leads to increased toxicity when the immunotherapy treatment works by affecting T cell function. One possible explanation is that the T cell response in the tumor tissue is beneficial, however, T cell response in the peripheral blood may indicate response against self antigens leading to toxicities in the form of irAE.

5553 Background: In patients with high-grade ovarian cancer in first-line setting, predictive factors of bevacizumab efficacy are needed, for selecting patients. In ICON-7 trial, a poor tumor intrisic chemosensitivity (defined by unfavorable modeled CA-125 kinetic ELIMination rate constant KELIM) was a predictive biomarker. Among patients with high-risk diseases, only those with unfavorable KELIM had survival benefit from bevacizumab (mOS: 29.7 vs 20.6 months, HR = 0.78)(Colomban. JNCI CS 2020). The objective was to perform an external validation in GOG-0218 trial (NCT00262847). Methods: In GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel +/- concurrent bevacizumab/placebo followed by a 15 month maintenance. Patient KELIM values were estimated with longitudinal CA-125 kinetics during the first 100 chemotherapy days. The association between KELIM score (categorized as favorable ≥ 1, or unfavorable < 1) and efficacy of bevacizumab (bevacizumab-concurrent + maintenance, vs placebo) for PFS and OS was assessed using univariate/multivariate analyses, in a Training set with 2/3 patients managed the investigators, and then a Validation set with all patients, managed by NGR-GOG. Results: KELIM was assessable in 1,662 patients with ≥ 3 CA-125 available values. In both sets, the patients with unfavorable KELIM derived benefit from bevacizumab compared to placebo (Training: PFS, HR = 0.65 [0.54-0.80]; OS, HR = 0.80 [0.65-0.99]; Validation: PFS, HR = 0.69 [0.59-0.82]; OS, HR = 0.87 [0.73-1.03]), whilst those with favorable KELIM had no benefit from bevacizumab (Training: PFS, HR = 0.96 [0.75-1.23]; OS, HR = 1.05 [0.80-1.37]; Validation, PFS, HR = 0.96 [0.79-1.17]; OS HR = 1.11 [0.89-1.84]). The highest benefit was observed in patients with high-risk diseases (stage IV or sub-optimally resected stage III) characterized by unfavorable KELIM, for PFS (Learning (n = 276): mPFS: 9.0 vs 5.2 months, HR = 0.61 [0.48-0.78]; Validation (n = 433): mPFS: 9.1 vs 5.6 months, HR = 0.64 [0.53-0.78]), and for OS (Learning (n = 278): mOS: 38.9 vs 27.9 months, HR = 0.72 [0.56-0.93], Validation set (n = 438): mOS: 35.1 vs 29.1 months, HR = 0.79 [0.65-0.97]). Conclusions: This validation analysis of GOG-0218 trial confirms the outcomes of ICON-7 trial about the association between poor tumor chemosensitivity and benefit from concurrent + maintenance bevacizumab, suggesting that bevacizumab is mainly effective in patients with poorly chemosensitive diseases. No benefit was found in patients with favorable KELIM. The patients who derived the highest benefit from bevacizumab in PFS and OS (OS absolute benefit ̃ 6 to 9 months) were those with high-risk diseases (stage IV, or incompletely resected stage III) associated with an unfavorable KELIM score (calculator on https://www.biomarker-kinetics.org/CA-125).

Peripheral blood interleukin 6, interleukin 10, and T lymphocyte levels are associated with checkpoint inhibitor induced pneumonitis: a case report

Background CRP is an acute-phase protein produced primarily in response to interleukin IL-6 via transcriptional activation of the STAT3. Recent data have provided mechanistic insights into the immune suppressive role of elevated CRP by elucidating its influence on effector T-cell function and antigen presentation.1 Furthermore, melanoma patients in Checkmate-064 and 067 with high baseline and on-treatment CRP were seen to have a lower response rate and shorter survival to immune checkpoint inhibitors (ICIs).2 Given these observations, we sought to evaluate the role of CRP as a prognostic biomarker in advanced NSCLC treated with ICIs from a multi-center international cohort. Methods Between 2015–2019, 420 adult patients with advanced NSCLC treated with ICIs alone or with concurrent chemotherapy (Chemo-ICI) were identified at four (1 US and 3 European) academic centers. CRP level in peripheral blood samples collected up to 2 weeks before starting ICI based treatments was considered as baseline. Based on previously validated data, a CRP cutoff of 10 mg/l was used to define CRP-normal (CRP-N) and CRP-high (CRP-H). Association of baseline CRP with median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and multivariate proportional hazards regression adjusted for multiple variables. Results Baseline CRP value was available in 75.5% of patients, with 66% having CRP-H. The median CRP was 21.0 mg/l. Single-agent nivolumab (44%) and Chemo-ICI (33.3%) were the two most common therapies. CRP-H showed a trend for stronger association with squamous histology (73.7% vs 63.3%; p= 0.063) and female sex (70.8 vs 60.0%; p=0.062) but did not show an association with PD-L1 status (0%, 1–49%, or ≥50%). Patients with CRP-H had a lower objective response rate compared with patients with CRP-N (26.9% vs. 47.6% PR; p=0.029). Compared to those with CRP-N (figure 1), patients with CRP-H had a significantly shorter median PFS [3.9 vs. 6.6 months, HR 1.41 95% CI: (1.07–1.86); p=0.0138] and OS (8.6 vs. 14.8 months, HR 1.55 95% CI [1.13- 2.14]; p=0.0060). In Cox regression analysis, CRP-H was again found to be independently associated with shorter median PFS and OS. Conclusions This is the largest international real-world dataset demonstrating significantly inferior outcomes associated with CRP > 10 mg/l in NSCLC patients treated with ICI based therapies. The potential influence of the immune suppressive effects of elevated CRP and IL-6 on the anti-tumor efficacy of ICIs needs prospective evaluation and could potentially be exploited as a therapeutic avenue in NSCLC. Acknowledgements Susan Eubanks and Sue-Ann Joyner at the ECU IRB for their help and support. Ethics Approval The primary IRB approval for this study was conducted under an ECU (P-MAIT- UMCIRB-15-001400). Individual approval was also obtained from the respective IRB of each participating institution. References Yoshida T, Ichikawa J, Giuroiu I, et al. C reactive protein impairs adaptive immunity in immune cells of patients with melanoma. Journal for ImmunoTherapy of Cancer 2020. Weber, et al. Journal of Clinical Oncology37, no. 15_suppl (May 20, 2019) 100–100

The impact of corticosteroid therapy (CT) on efficacy of immune checkpoint inhibitors (ICI) is undefined in hepatocellular carcinoma (HCC). We evaluated whether CT administered at baseline (bCT) or concurrently with ICI (cCT) influences overall (OS), progression-free survival (PFS) and overall response rates (ORR) in 341 patients collected across 3 continents. Of 304 eligible patients, 78 (26%) received >10 mg prednisone equivalent daily either as bCT (n=14, 5%) or cCT (n=64, 21%). Indications for CT included procedure/prophylaxis (n=37, 47%), management of immune-related adverse event (n=27, 35%), cancer-related symptoms (n=8, 10%) or comorbidities (n=6, 8%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in univariable and multivariable analyses (p>0.05). CT for cancer-related indications predicted for shorter PFS (p

BackgroundNivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.Patients and methodsWe performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.ResultsPatients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line (n=148, 63.5%). Objective response rate (ORR) was 22.4% and disease control rate was 52.1%. Median overall survival (OS) was 12.2 months (95% CI 8.4 to 16.0) and median progression-free survival was 10.1 months (95% CI 6.1 to 14.2). Treatment-related adverse events of grade >2 occurred in 26 patients (11.2%). Efficacy and safety were similar across CP classes and therapy line. OS was shorter in CP-B than A (7.3 months vs 16.3 months, p=0.05). Achievement of an objective response predicted for improved OS (25.4 months vs 13.2 months, pConclusionsThis study confirms safety and efficacy of nivolumab in advanced HCC across various lines of therapy and degrees of liver dysfunction. Despite equal ORR and toxicity to nivolumab, patients with CP-B functional class have shorter survival than the patients with CP-A.

Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied 341 patients treated with programmed-death pathway inhibitors (n = 290, 85%). Pre-treatment ALBI independently predicted for OS, with median OS of 22.5, 9.6, and 4.6 months across grades (p &lt, 0.001). ALBI was superior to CTP in predicting 90-days mortality with area under the curve values of 0.65 (95% CI 0.57&ndash, 0.74) versus 0.63 (95% CI 0.54&ndash, 0.72). ALBI grade at ICI cessation independently predicted for PIOS (p &lt, 0.001). Following adjustment for ICI regimen, neither ALBI nor CTP predicted for overall response rates or treatment-emerging adverse events (p &gt, 0.05). ALBI grade identifies a subset of patients with prolonged survival prior to and after ICI therapy, lending itself as an optimal stratifying biomarker to optimise sequencing of systemic therapies in advanced HCC.

399 Background: Portal hypertension increases intestinal permeability, dysbiosis, and bacterial translocation, leading to a pro-inflammatory state, which can in turn promote progression of liver disease. However, multiple studies have shown that BB use in patients with cirrhosis can reduce the risk of developing HCC, and in patients with HCC, BB can improve overall survival (OS). In recent years, ICIs have become first-line therapy for patients with unresectable HCC, and we aimed to evaluate whether BB use conferred survival benefits in patients treated with ICIs using real-world data. Methods: We conducted a retrospective chart review of HCC patients treated with ICI from 2017 to 2019 at 13 institutions across North America, Europe, and Asia in order to evaluate the association between BB use and OS, as well as BB use and overall response rate (ORR). Univariable and multivariable logistic regression models were used to evaluate associations, and survival analyses were performed using the Kaplan-Meier method. Results: A total of 578 patients were evaluated. The median age of the cohort was 65 years, and 80% of patients were male. The majority of patients (70%) were cirrhotic. The causes of underlying liver disease were as follows: HBV (22%), HCV (36%), alcohol (20.8%), and NASH (13%). Most patients (73.5%) had Child Pugh (CP) class A liver disease, and good performance status with ECOG score either 0 (52%) or 1 (45%). The majority of patients (75%) treated with ICIs received a PD-1 inhibitor alone. There were 360 deaths (62% of patients) with a median follow-up of 30.8 months (Quartiles: 17.2-40.3 months). Two hundred and three (35%) patients had BB use at any point during ICI therapy. Fifty-one percent of these patients were on a nonselective BB whereas 49% were taking a cardio-selective BB. BB use was not significantly correlated with OS (hazard ratio, 1.12; 95% CI, 0.9-1.39; P = 0.298) or ORR (odds ratio, 0.84; 95% CI, 0.54-1.31; P = 0.451) in univariate or multivariate analyses. Conclusions: Patients who used BB while on immunotherapy for unresectable HCC did not have statistically significant differences in OS or ORR compared to patients who did not use BB. More studies are required to elucidate the effect of beta blockade on the microbiome, immune activation, and HCC.

Primary tumor resection (PTR) in metastatic breast cancer is not a standard treatment modality, and its impact on survival is conflicting. The primary objective of this study was to analyze impact of PTR on survival in metastatic patients with breast cancer. A retrospective study of metastatic patients with breast cancer was conducted using the 1988-2011 Surveillance, Epidemiology, and End Results (SEER) data base. Cox proportional hazards regression models were used to evaluate the relationship between PTR and survival and to adjust for the heterogeneity between the groups, and a propensity score-matched analysis was also performed. A total of 29 916 patients with metastatic breast cancer were included in the study, and 15 129 (51%) of patients underwent primary tumor resection, and 14 787 (49%) patients did not undergo surgery. Overall, decreasing trend in PTR for metastatic breast cancer in last decades was noted. Primary tumor resection was associated with a longer median OS (34 vs 18 months). In a propensity score-matched analysis, prognosis was also more favorable in the resected group (P = .0017). Primary tumor resection in metastatic breast cancer was associated with survival improvement, and the improvement persisted in propensity-matched analysis.

Background: Disparity in demographic characteristics as it relates to breast cancer outcomes is well-studied. However, studies evaluating racial differences exclusively among young patients are more limited. We sought to examine socioeconomic and clinical factors and their impact on outcomes in young patients, as well as to determine whether variation in outcomes changed over the 22-year study period. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified female patients aged 20-35 with invasive breast cancer diagnosed from 1990-2012. We performed univariate, multivariate and survival analysis. Variables included patient age, race, stage, receptor status, surgery type and year of diagnosis Results: A total of 18,999 women were identified and analyzed. Mean age was 31.7 years. 31.2% were diagnosed between 1990-2000 while 68.7% were diagnosed between 2001-2012. 80.8% (15,364) of patients were white and 19.1% (3,635) were black. A higher percentage of blacks had stage III/IV disease (34% v 27%) and ≥ 4 positive nodes (19% v 16%) compared to whites. 54% of whites were ER receptor positive while 46% of blacks were ER receptor positive (p The overall 5-year disease specific survival (DSS) for the entire cohort was 82.5%. 5-year DSS was 84.4% for all white patients and 74.2% for all black patients (p Discussion: Racial disparity among breast cancer patients is also an issue in young females, as young white patients have superior disease-specific survival compared to African-Americans collectively and in each time-period studied. Absolute disease-specific survival has improved from 1990-2000 to 2001-2012 for both races. However, the statistically significant difference in improvement of disease-specific survival seen among white patients was not demonstrated in African-American patients. Continued attention to racial disparity in breast cancer outcomes is needed with additional studies examining potential differences in treatment, disease characteristics and biology, and accessibility to health care, with a particular focus on young cancer patients. With continued research, hopefully new treatment approaches will be developed to reduce this disparity. 5-Year Disease Specific SurvivalTime Period5 year DSSp value WhiteBlack 1990-200080.9%71.3%0.00012001-201286.3%75.7%0.0001p value0.00010.24 Survival by stage 5 yr DSS WhiteBlackp valueStage I96.2%94.9% Citation Format: McClain JT, Mosquera C, Muzaffar M. Racial differences in the characteristics and outcomes of young breast cancer patients: A national population-based study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-10-06.

Background: Screening mammogram has resulted in increased diagnosis of very small breast cancers, especially less than 1 cm node negative. These small tumors have excellent prognosis with cancer-specific survival rates as high as 90% to 95%. This study evaluates outcome in different subtypes of very early breast cancer in a national population database. Method: Patients with stage I breast cancer, tumor ≤ 1cm with negative nodes (T1aN0 ( Results: We identified 70,543 cases and included 54,796 patients with stage T1aN0M0 and T1bN0M0 in the final analysis. The mean age was 62.09 yrs. (CI 95% 62.2-61.99), 84% are white, 7% black and 7% others.89% had ER positive tumor, 11% ER negative and 3% had Her 2 positive tumors.71% of patients had T1b (≤ 1cm). The 5-year disease specific survival (DSS) and overall survival (OS) for patients with stage T1aN0, T1bN0 was 98.7% and 93.7%, respectively. Estrogen receptor (ER) positive tumors were associated with improved 5-yr DSS 99% vs. 96% in ER negative (p Conclusions: Very early breast cancer is associated with excellent outcome but has some heterogeneity. Nonwhite/Non Black race was associated with better survival compared to white and black patients. ER positive tumors, and older age were also associated with better outcome. This data while reassuring also brings into question the overtreatment of this disease subset. One of the limitations of this dataset is lack of details of systemic therapy administered. Conventional prognostic factors are not sufficient to risk stratify very early breast cancer and molecular profiling may help identify patients who will need adjuvant treatment. Citation Format: Muzaffar M, Namireddy P, Naqash R, Wong J, Vohra N. Outcome of small (≤1 cm), node-negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-15-04.

Co-relation of overall survival with peripheral blood-based inflammatory biomarkers in advanced stage non-small cell lung cancer treated with anti-programmed cell death-1 therapy: results from a single institutional database

Background: Acute-phase reactants, such as C-reactive protein (CRP) and IL-6, can modulate immune suppression within the tumor microenvironment (TME) and thus potentially result in inferior outcomes to immune checkpoint inhibitors (ICIs). Immunosuppression within the TME is also be mediated by tumoral adenosine production, via hypoxia-induced exonuclease activity of CD39 and CD73 and adenosine 2a receptor (A2aR) signaling. We sought to evaluate whether plasma levels of A2aR correlate with the acute phase reactants (CRP and IL-6) in advanced NSCLC patients treated with ICIs. Methods: Between December 2016 and April 2019, we enrolled 18 patients with advanced NSCLC treated with single-agent ICIs or in combination with chemotherapy. We isolated plasma samples from patients before ICI initiation and again after each treatment. Plasma concentrations of A2aR and IL-6 were measured using ELISA. The baseline level of CRP was obtained from peripheral blood at ICI initiation (± 3 days). Previous studies correlating CRP and cancer outcomes defined a C-reactive protein (CRP) cutoff of 10 mg/L to define normal (CRP-N) and high CRP (CRP-H) levels. We assessed the relationship between CRP, IL-6, and A2aR plasma levels. Statistical analyses were performed using the Mann-Whitney test and linear regression analysis. Results: At the initiation of ICI, the median age of the cohort was 63. Two patients had stage III disease and 16 patients had stage IV disease. Four had squamous cell carcinoma, and 14 had non-squamous cell carcinoma. Six patients were treated with concomitant chemotherapy (pembrolizumab with carboplatin and pemetrexed). Patients received a median of 4 ICI cycles (range: 1-8 cycles) in our study. In the cohort, the median baseline levels of CRP, IL-6, and A2aR were 16.9 mg/L, 5.1 pg/mL, and 3.6 ng/mL, respectively. A positive correlation was present between baseline CRP levels and IL-6 plasma levels (R=0.76; p=0.003). Seven patients were CRP-N, and 11 patients were CRP-H. CRP-H patients had a greater median baseline level of A2aR (6.0 ng/mL vs. 1.3 ng/mL; p=0.01). Likewise, patients with baseline IL-6 levels greater than 5 pg/mL had a higher median baseline level of A2aR (6.0 ng/mL vs. 1.3 ng/mL; p=0.02). Conclusions: In a small, heterogeneous cohort of advanced NSCLC patients treated with ICIs, we demonstrate that elevated baseline levels of acute-phase reactants (CRP and IL-6) potentially act as an indirect surrogate for high plasma A2aR levels. Validation from larger studies is required to understand the biomarker implications of these findings in determining outcomes to ICIs. J.D.M. and A.R.N contributed equally to this work. Citation Format: Justin D. McCallen, Abdul R. Naqash, Mona A. Marie, Nitika Sharma, Mahvish Muzaffar, Paul R. Walker, Li Yang. A pilot study correlating baseline plasma levels of adenosine 2A receptor (A2aR) with acute phase reactants in advanced non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1667.

Background: Immune checkpoint inhibition (ICI) is an expanding option in hepatocellular carcinoma (HCC). Antibiotics (ATB) have been shown to reduce response and survival after ICI in other cancers. Methods: Efficacy of ICI is described in patients (pt) from 11 centres (246 USA, 100 Asia, 68 Europe), with median overall (OS), progression-free survival (PFS) and best response (RECIST 1.1) compared between pt with and without ATB exposure in the early immunotherapy period (EIOP) of 30 days before and after ICI initiation. Results: Most of our 414 pt were cirrhotic (297, 71.7%) due to hepatitis C (162, 391.1%) with Barcelona Clinic Stage C (294, 71.0%), Child-Pugh class (CP) A (313, 76.3%) and AFP>400 IU/mL (158, 39.3%). OS was 15.4 mo (95%CI 13.1-17.7) and PFS was 5.3 months (95% CI 4.5-6.0). Most ICI was anti-PD-1 monotherapy (358, 86.5%) and given as 1st (173, 41.8%) or 2nd line (208, 50.2%). Best response to ICI was complete response in 27 pt (6.5%), partial response in 45 (10.9%), stable disease (SD) in 160 (38.6%) and progressive disease (PD) in 161 (38.9%). ATB was given to 167 pt (40.3%), prior to or early after (30 d) ICI initiation (EIOP, 157, 38.0%) or beyond 30 days (21, 5.1%), mostly as beta-lactams (27, 10.9%) or quinolones (26, 10.5%). ATB use was independent of CP class (p=0.76), ECOG performance status (p=0.58) and BCLC stage (p=0.60). mOS in the EIOP+ group was similar to the EIOP- group (13.1 vs 15.5 mo, p=0.92). mPFS in the EIOP+ group was significantly longer than the EIOP- group (7.9 vs 4.2 mo, p=0.004). Observations persisted when stratified by CP class (p=0.42) and ICI type (p=0.92). Partial response rate was higher in the EIOP+ group (17.3% vs 8.6%, p=0.01), although overall objective response and disease control rates were similar between EIOP groups (ORR: 22.7% vs 15.9%, p=0.10; DCR: 64.0% vs 56.6%, p=0.15). Pt in the EIOP+ group were not more likely to experience gastrointestinal AE (EIOP +/- 9.2%/5.4%, p=0.12) or hepatic AE (EIOP +/-, 17.9%/16.5%, p=0.92) of any grade, while severe liver AE (grade 2 or above) were less common in the EIOP+ group (EIOP+/- 2.8%/9.5%, p=0.01). Conclusions: ATB in the 30 d before or after ICI initiation in HCC is associated with prolonged PFS. This is contrary to findings in other solid tumors. Evaluation of the immune-microbiologic determinants of response to ICI in HCC a key research question. Citation Format: Petros Fessas, Muntaha Naeem, Thomas U. Marron, David Szafron, Elad Sharon, Anwar Saeed, Tomi Jun, Sirish Dharmapuri, Abdul R. Naqash, Thoetchai Peeraphatdit, Anuhya Gampa, Yinghong Wang, Uqba Khan, Mahvish Muzaffar, Musharraf Navaid, ChiehJu Lee, Pei-Chang Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I. Abugabal, Tiziana Pressiani, Nicola Personeni, Naoshi Nishida, Masatoshi Kudo, Ahmed Kaseb, Yi-Hsiang Huang, Celina Ang, Anjana Pillai, Lorenza Rimassa, David J. Pinato. Early antibiotic exposure delays disease progression following immune checkpoint inhibitor therapy for hepatocellular carcinoma: Evidence from an observational study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 485.