Shorter Median Progression-free Survival Research Articles

Systemic therapy in patients with metastatic Xp11.2 translocation renal cell carcinoma.

341 Background: Xp11.2 translocation renal cell carcinoma (RCC) is a unique RCC subtype with high malignant potential and poor prognosis, its natural course and response to systemic therapy are not fully understood. We analyzed the clinic features of this distinct entity and the benefit of systemic therapy in these patients. Methods: Between May 2006 and December 2019, 1113 consecutive patients diagnosed with RCC from Peking university cancer hospital (Beijing, China) were reviewed, data of the clinical characteristics and outcome of patients with metastatic Xp11.2 RCC were retrospectively collected. Tumor response to systemic therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results: Metastatic Xp11.2 tRCC was found in 45 patients. The median PFS and median OS was 7.4 months (4.5 - 8.8) and 17.9 months (12.4 - 24.4), respectively. First-line treatment mainly included sunitinib (n = 14), sorafenib (n = 15), axitinib (n = 6), and pazopanib (n = 5), and the median PFS of these regimens were 7.4 months, 5.4 months, 9.4 months, 8.9 months, respectively. Two patients who received Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) plus immune checkpoint inhibitor (ICI) as first line therapy had a PFS of more than 16.6 months and more than 25.6 months, respectively. Twenty-four patients received subsequent therapies, which included VEGFR-TKI/ICI, axitinib and mTOR inhibitor, the median PFS for these regimens was 8.5, 7.2 and 2.0 months, respectively. Patients with serous cavity effusion or IMDC poor risk groups had significantly shorter median PFS and median OS. Conclusions: Metastatic Xp11.2 tRCC is an aggressive disease. VEGFR-TKI agents appeared to demonstrate some efficacy, VEGFR-TKI/ICI combination might be a useful tool for the treatment of metastatic Xp11.2 tRCC.

Abstract P5-13-24: Efficacy of first line CDK4/6 inhibitors in HER2-low vs HER2-zero, hormone receptor positive, HER2 negative metastatic breast cancer

Abstract Introduction: CDK4/6 inhibitors are the standard of care in the vast majority of patients with metastatic breast cancer (MBC) in first line setting. HER2-low expression, defined as IHC score of 1+ or 2+ with negative ISH assay, has been associated with resistance to CDK4/6 inhibitors. This has not yet been explored for advanced disease in the first line setting. We aimed to analyze the efficacy of CDK4/6 inhibitors in this subset of patients compared to HER2-zero tumors. Methods: We identified patients with positive hormone receptors and HER2 negative metastatic breast cancer treated with first line CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) and letrozole or fulvestrant between December 2017 - April 2021 in our institution (Hospital 12 de Octubre, Madrid, Spain). HER2 expression and PAM50 subtypes were analyzed in metastatic tissue samples for all patients. For the analysis, patients were classified as HER2-zero or HER2-low groups. Our main objective was to evaluate the relationship between HER2 expression and progression-free survival (PFS) with log-rank test. Multivariable Cox regression model was used to estimate the adjusted hazard ratio (HR). As secondary objectives, we analyzed this association in all CDK4/6 subgroups and described the prevalence of PAM-50 subtypes in each category (HER2-low and HER2-zero). Results: We included 82 patients in our final analysis. 57% of the patients were classified in the HER2-low category. In our sample, 49% of patients received palbociclib, 39% ribociclib and 12% abemaciclib. A high proportion of patients presented visceral disease (75% in the HER2-zero vs 60% in the HER2-low group). Only 20% of tumors were considered as hormone-resistant. The overall response rate was slightly higher in the HER2-zero category (41% vs 35% in the HER2-low). With a median follow-up of 14 months (2 - 48 months), the median PFS was 31.7 months (95%CI: 20.3 - NR months) in the HER2-zero category and 22.8 months (95%CI: 15.7 - NR months) in the HER2-low (p=0.37). In the multivariable Cox regression model, HER2-low tumors were associated with a non-significantly higher risk of progression (HR=1.62; CI 95%:0.74-3.54). In patients treated with palbociclib, the median PFS for HER2-zero vs HER2-low categories were 31.7 months and NR (p=0.79), respectively. For ribociclib, the HER2-zero had a median PFS of 38.4 months and 33.1 months in the HER2-low category (p=0.47). In patients treated with abemaciclib, median PFS was NR for HER2-zero group and 9.2 months for HER2-low (p=0.18). The interaction test between HER2 categories and CDK4/6 inhibitors was not statistically significant (p=0.48). PAM-50 subtypes information was available for 47 patients. In these patients the prevalence of PAM-50 subtypes showed a relative higher proportion of luminal subtypes in the HER2-zero category (95%) and non-luminal (HER2-enriched and normal-like subtypes) in the HER2-low category (21%). Conclusions: In our sample, HER2-low category had a shorter median PFS in first line treatment with CDK4/6 inhibitors plus endocrine treatment compared to HER2-zero group. This finding was consistent for the three CDK4/6 inhibitors analyzed, although the HER2-low group showed more relative benefit in terms of PFS with palbociclib. Our results suggest a lower benefit of CDK4/6 inhibitors in the first line treatment of HER2-low MBC, which could be partially explained by a relative higher proportion of non-luminal PAM-50 subtypes in HER2-low tumors. FundingThis project has received a research grant from “Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad” (Spain) awarded within the National Research Program with reference PI 18/01408, co-funded with European Union ERDF funds (European Regional Development Fund). Citation Format: Rodrigo Sanchez-Bayona, Santiago Terán, Ana Sánchez De Torre, Manuel Alva, Laura Lema, Luis Manso, Estefanía Toledo, Ana Maria Roncero, Cristina Merino, Mario Martínez, Lucía Parrilla, Eva Ciruelos, Pablo Tolosa. Efficacy of first line CDK4/6 inhibitors in HER2-low vs HER2-zero, hormone receptor positive, HER2 negative metastatic breast cancer [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 P5-13-24.

Abstract PD13-03: Ribociclib, everolimus, exemestane triplet therapy in HR+/HER2− advanced breast cancer after progression on a CDK4/6 inhibitor: Final efficacy, safety, and biomarker results from TRINITI-1

Abstract PD13-03: Ribociclib, everolimus, exemestane triplet therapy in HR+/HER2− advanced breast cancer after progression on a CDK4/6 inhibitor: Final efficacy, safety, and biomarker results from TRINITI-1

Prognostic Significance of the Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Neuroendocrine Carcinoma.

Extra-pulmonary neuroendocrine carcinoma is a rare and aggressive cancer. Although several biological and histological markers have been suggested as prognostic factors for this cancer, the prognostic importance of systemic inflammatory markers, including the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, is unclear. This study aimed to evaluate the association between systemic inflammatory markers and the prognosis of extra-pulmonary neuroendocrine carcinoma. We retrospectively analyzed the clinical data of 85 patients with unresectable or metastatic extra-pulmonary neuroendocrine carcinoma who received platinum-based chemotherapy as first-line chemotherapy from August 2007 to November 2019. We used time-dependent receiver operating characteristic curve analysis to determine the cut-off values. The cut-off values for the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 3.0 and 158.5, respectively. There was no significant difference in the Eastern Cooperative Oncology Group performance status score, Ki-67 index, or response to chemotherapy between groups. The high neutrophil-lymphocyte ratio group showed significantly worse overall survival (high vs. low, median 11.1 vs. 21.0 months, log-rank p=0.004) and shorter median progression-free survival, but the latter was not statistically significant. The high platelet-lymphocyte ratio group also showed significantly worse progression-free survival and overall survival than the low platelet-lymphocyte ratio group (high vs. low: median 5.6 vs. 9.8 months, log-rank p=0.047 and median 13.8 vs. 21.0 months, log-rank p=0.013, respectively). In multivariable analysis, a high neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival. The neutrophil-lymphocyte ratio is a potent and readily available prognostic factor for extra-pulmonary neuroendocrine carcinoma.

Rituximab, Methotrexate, Carmustine, Etoposide, and Prednisone (RMBVP) for the treatment of relapsed/refractory primary central nervous system lymphoma: a retrospective single-center study

Relapsed/refractory Primary Central Nervous System Lymphoma (R/R PCNSL) has a poor prognosis with no established preferred treatment. We report the efficacy and toxicity of a combination chemotherapy regimen: methotrexate, carmustine, etoposide, and prednisone with or without rituximab (RMBVP). This retrospective study included thirty patients who received a median of two 28-day cycles (0.5–5). The median age was 66 years (23–81); median KPS was 70 (30–90); 14 (46.7%) were women. Patients received a median of 2 prior lines of therapy and all received prior methotrexate. Of 29 evaluable patients, the overall response rate was 73.3% (n = 22). Median progression-free survival (PFS) was 15.6 months. Patients who recurred or progressed <12 months since last chemotherapy had a shorter median PFS (7.6 vs 37.6 months). Toxicity was moderate with 20% rates of severe myelosuppression. RMBVP is a tolerable treatment option for R/R PCNSL, with favorable response rates in those with recurrent disease.

A Multi-Center Retrospective Study of Polatuzumab for Patients with Large B-Cell Lymphoma Relapsed after Standard of Care CAR T-Cell Therapy

A Multi-Center Retrospective Study of Polatuzumab for Patients with Large B-Cell Lymphoma Relapsed after Standard of Care CAR T-Cell Therapy

P13.01 Use of Antibiotics Is Associated With an Increase in Immunotherapy Related Adverse Effects in Patients With Non-Small Cell Lung Cancer

Immune check point inhibitors (ICI) are the backbone of treatment in patients with metastatic non-small cell lung cancer (NSCLC). Around 40-70% of treated patients experience either single or multisystem immune related adverse events (irAEs) leading to permanent discontinuation of ICI therapy in 10-15% of such patients, which is associated with shorter median progression free survival (PFS) and overall survival (OS). Some studies have shown that use of antibiotics in this setting is associated with increase risk of irAEs and hospitalizations.

Molecular Alterations and Their Correlation With the Survival of Glioblastoma Patients With Corpus Callosum Involvement.

Purpose: To explore molecular alterations and their correlation with the survival of patients with glioblastoma (GBM) with corpus callosum (CC) involvement (ccGBM).Methods: Electronic medical records were reviewed for glioma patients tested for molecular alterations and treated at our hospital between January 2016 and July 2020. ccGBM was compared to GBM without CC involvement (non-ccGBM) to identify differences in molecular alterations. Clinical outcomes and survival were compared between ccGBM and non-ccGBM patients, as well as among patients with ccGBM with different molecular alteration statuses. ccGBM was also compared to diffuse midline glioma (DMG) to clarify their correlation in molecular alterations, the progression-free survival (PFS), and overall survival (OS).Results: Thirty ccGBM and 88 non-ccGBM patients were included. PDGFRA amplification (PDGFRAamp, 33.3 vs. 9.1%, P = 0.004) and missense mutation (PDGFRAmut, 20.0 vs. 3.4%, P = 0.011) both had higher incidences in ccGBM than in non-ccGBM. PDGFRA alteration was associated with the occurrence of ccGBM (OR = 4.91 [95% CI: 1.55–15.52], P = 0.007). ccGBM with PDGFRAamp resulted in a shorter median PFS (8.6 vs. 13.5 months, P = 0.025) and OS (12.4 vs. 17.9 months, P = 0.022) than non-ccGBM with PDGFRAnon-amp. ccGBM with PDGFRAamp combined with PDGFRAmut (PDGFRAamp-mut) had a shorter median PFS (7.6 vs. 8.9 months, P = 0.022) and OS (9.6 vs. 17.8 months, P = 0.006) than non-ccGBM with wild-type PDGFRA and no amplification (PDGFRA-w, non-amp). Compared to ccGBM with PDGFRA-w, non-amp, ccGBM with PDGFRAamp and PDGFRAamp-mut both had a shorter median PFS and OS (P < 0.05). The hazard ratios (HRs) of PDGFRAamp for PFS and OS in ccGBM were 3.08 (95% CI: 1.02–9.35, P = 0.047) and 5.07 (1.52–16.89, P = 0.008), respectively, and the HRs of PDGFRAamp-mut for PFS and OS were 13.16 (95% CI: 3.19–54.40, P < 0.001) and 16.36 (2.66–100.70, P = 0.003). ccGBM may have similar incidences of PDGFRAamp or mut (PDGFRAamp/mut) as DMG, and they also had similar median PFS (10.9 vs. 9.0 months, P = 0.558) and OS (16.8 vs. 11.5 months, P = 0.510).Conclusion:PDGFRA alterations are significantly associated with the occurrence and poor prognosis of ccGBM. ccGBM with PDGFRAamp/mut may be classified as a single subtype of GBM that has a similar survival rate to DMG. PDGFR inhibitors may be a promising treatment method for ccGBM.

Treatment Patterns and Survival Outcomes in Latin American Patients with Newly Diagnosed Multiple Myeloma: A Retrospective Medical Chart Review Study, 2008-2016

Background: Recent advances in multiple myeloma (MM) treatment have led to overall improvement in patient outcomes around the world, although the incorporation of novel therapies is generally slow in Latin American countries. Currently, there is limited real-world evidence on available therapies and associated patient outcomes in this region.Objective: To evaluate the treatment landscape by examining up to 3 lines of therapy (LOTs) in Latin American patients with MM diagnosis and the impact of therapies on outcomes of progression-free survival (PFS) and overall survival (OS).Methods: Medical chart review was performed for patients with newly diagnosed MM at 30 participating clinical sites in 7 Latin American countries: Argentina, Brazil, Chile, Colombia, Mexico, Panama and Guatemala. All patients were followed from initiation of 1st LOT to the earliest of end of follow-up or death date (OS). PFS in each LOT was determined from initiation of each LOT until the earliest of end of follow-up, relapse date or death date. A multivariable Cox proportional hazard regression model was used to assess the association of therapy choice in 1st and 2nd LOTs with risk for disease progression or death, comparing patients with bortezomib (V)-based therapy against patients with other therapies. Patients receiving stem cell transplant were excluded from the analysis.Results: We identified1104 MM patients at initiation of 1st LOT with median age at diagnosis of 61 years. Median follow-up was 27 months; 48% patients had a history of cardio-related disease and 12% had a history of renal impairment. During the follow-up, 504 (46%) patients subsequently received a 2nd LOT, and 133 (12%) patients received additional 3rd LOT.Across all 1st, 2nd and 3rd LOTs, the 3 most commonly used regimens were thalidomide (T)-based regimen (excluding bortezomib), V-based regimen (excluding immunomodulators), and chemotherapy alone, accounting for 94%, 84% and 74% of 1st, 2nd and 3rd LOTs, respectively. T-based therapy was predominantly used in the 1st LOT and less often in subsequent LOTs, whereas use of V-based regimen and chemotherapy remained constant across the 3 LOTs (Table 1). Only a small proportion of patients were retreated by the same therapy, with 92 (18%) T-based patients, 28 (6%) V-based patients and 14 (3%) chemotherapy patients in both 1st and 2nd LOTs.With a median PFS time of 19 months in the 1st LOT, landmark PFS at year 1, 2, and 3 was 62%, 31% and 16%, respectively. Patients with T-based or chemo-therapy in their 1st LOT had ≥41% increased risk for relapse during 1st LOT than those with V-based therapy (p<0.01, Table 2a). In 2nd LOT, the median PFS was 10 months; landmark PFS at year 1, 2 and 3 was 36%, 13% and 5%, respectively. No statistical differences in landmark PFS for 2nd LOT were observed among the 3 treatments (p≥0.09, Table 2b).Following initiation of 1st LOT, 357 (32%) patients died. In 1st LOT, OS rate at year 1, 2, and 3 was 84%, 55% and 35%. There was no difference in mortality risk between patients using T- and V-based therapy (p=0.95), although chemotherapy patients had 43% increased mortality relative to V-based patients (p<0.05, Table 2c). Similar association was also observed in 2nd LOT (Table 2d), with median OS time of 17 months.When individual countries were assessed in 1st LOT, Brazilian patients, relative to those in other 6 countries, had shorter median PFS (10 months) and median OS time (23 months). Common treatments in Brazil across the 3 LOTs were similar to those in other countries. Also, a somewhat stronger association between treatment choice and outcomes of PFS and OS was seen in Brazil (Table 3).Conclusion: This study shows the latest findings of treatment patterns and associated outcomes in MM patients from 7 Latin American countries. The continued high prevalence of T-based therapy use after 2008 in these patients suggests that several Latin American countries have limited treatment options. Following initiation of 1st LOT, ~70% patients experienced 1st disease progression within 2 years and >40% of patients died from the disease. Brazilian patients appear to have worse PFS and OS in 1st LOT than patients from other countries, likely attributable to treatment choice. Better management of care for MM, such as increased use of novel agents and new treatment sequence are needed to prolong PFS and OS in these patients. [Display omitted] DisclosuresHungria:Celgene, Roche, Takeda, Janssen, Amgen: Honoraria. Miguel:Janssen: Speakers Bureau. Silvana Cugliari:Roche, Raffo, Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Santos:Janssen: Employment. Santos:Janssen: Employment. Machnicki:Janssen: Employment. Lin:Janssen: Employment. Chen:Janssen: Employment. Barreyro:Janssen: Employment.

Profiling heterogenous sizes of circulating tumor microemboli to track therapeutic resistance and prognosis in advanced gastric cancer

Circulating tumor microemboli (CTM) aggregated by ≥ 2 circulating tumor cells (CTCs) are more migratory than single CTCs. Aside from the plasticity in their molecular characteristics, which have been considered tumor migration, CTM also possesses high size heterogeneity. This study, therefore, systematically investigated the heterogeneous sizes of CTM and their involvement in therapeutic resistance in 114 patients with advanced gastric cancer (GC) using a pre-established surface molecule-independent subtraction enrichment (SE)-iFISH strategy. CTM, which was pre-therapeutically detected in 33.3% of GC patients, can further form in another 34.78% of patients following chemo-/targeted therapies. The presence of CTM is relevant to liver metastasis as well as higher CTC levels (≥ 5/6 mL). Further size-based profiling of GC-CTM revealed that CTM with 2 CTCs (CTM2) was the dominant subtype, accounting for 50.0% of all detected GC-CTMs. However, CTM with 3–4 CTCs (CTM3–4) specifically associates with chemo-/targeted therapeutic resistance and inferior prognosis. Patients with ≥ 1 CTM3–4/6 mL have shorter median progression-free survival and median overall survival. Unlike CTM2 and CTM3–4, which are detectable in pre-therapy and post-therapy, larger aggregated CTM≥5 (CTM with ≥ 5 CTCs) was only intra-therapeutically detected in four HER2+ GC patients, of which three experienced liver metastases. Obtained results suggested that the cluster size of GC-CTM should be dynamically profiled beyond pre-therapeutic whole CTM enumeration in terms of chemo-/targeted resistance or metastasis monitoring. GC-CTM3–4 could be a potential indicator of therapeutic resistance, while the dynamic presence of GC-CTM≥5 implies liver metastasis in HER2+ GC patients.

CLINICAL OUTCOMES IN PATIENTS RELAPSED/REFRACTORY AFTER ≥ 2 PRIOR LINES OF THERAPY FOR FOLLICULAR LYMPHOMA: A SYSTEMATIC LITERATURE REVIEW AND META‐ANALYSIS

Introduction: Patients with follicular lymphoma (FL) can have high response rates to early lines of treatment. However, among FL patients relapsed/refractory (r/r) after ≥2 prior lines of therapies (LOT), remission tends to be shorter and there is limited treatment guidance. This study sought to evaluate the clinical outcomes for r/r FL after ≥2 prior LOT using available treatment options. Methods: Electronic databases were searched on 2nd June 2020. Eligible studies were comparative or non-comparative interventional or observational studies of systemic therapies among adults with FL r/r after ≥2 prior LOT. Prior LOT must have included anti-CD20 monoclonal antibodies and alkylating agents, in combination or separately. Overall response rate (ORR) and complete response (CR) were analyzed using inverse-variance weighting with Freeman-Tukey double-arcsine transformations. Kaplan-Meier (KM) analysis for progression-free survival (PFS) and overall survival (OS) were conducted using digitized curves and the Guyot algorithm. Survival analyses were stratified by ≥2 prior LOT and ≥3 prior LOT groups and were restricted to the observational cohorts as a sensitivity analysis. Results: The meta-analysis included 12 studies published from 2014-2020. Sample size for response outcomes was 340, for survival outcomes with ≥2 prior LOT was 1024 and for ≥3 prior LOT was 502. The estimated ORR in the ≥2 prior LOT group was 56.0% (95% confidence interval [CI]: 47.2 – 64.5) and proportion of patients with CR was 12.2% (95% CI: 8.0 – 17.3). The median OS was 54.4 months (95% CI: 45.8 – 76.0) and median PFS was 10.3 months (95% CI: 9.3 – 11.1). The 24-month OS decreased from 66% in the ≥2 prior LOT group to 60% in the ≥3 prior LOT group (Table 1), with a similar trend in PFS at 24-month (28% vs 24%). Conclusions: This study found that few r/r FL patients with ≥2 prior LOT achieve CR, and despite some benefit, approximately 1/3 of patients die within 24 months. The shorter median PFS with increasing prior LOT suggest treatment durability is suboptimal in later LOT. These findings indicate that patients are underserved by current treatments, demonstrating a need for new treatments that can achieve high rates of durable response in this disease. EA – previously submitted to ASCO and EHA 2021. The research was funded by: This project was funded by Kite, a Gilead company. Keywords: Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract S. Kanters Employment or leadership position: RainCity Analytics Research funding: RainCity Analytics has received funds from for-profit healthcare companies for research B. Kahl Consultant or advisory role: Abbvie, Acerta, AstraZeneca, Celege, Kite, Genentech, Pharmacyclics, MEI Research funding: Genentech, Celgene, Acerta, AstraZeneca A. Wiesinger Employment or leadership position: Kite, A Gilead Company Stock ownership: Kite, A Gilead Company B. Gurung Employment or leadership position: IQVIA Ltd Research funding: IQVIA Ltd E. H Limbrick-Oldfield Employment or leadership position: RainCity Analytics A. Sudhindra Employment or leadership position: Atara Biotherapeutics, Kite Pharma Stock ownership: Atara Biotherapeutics, Gilead J. Thornton Snider Employment or leadership position: Kite, A Gilead Company Stock ownership: Gilead Sciences Research funding: Previously employed at PrecisionHEOR, which receives research funding from life sciences companies. A. R Patel Employment or leadership position: Kite, A Gilead Company Stock ownership: Kite, A Gilead Company

Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC).

1077 Background: In pts with pretreated mTNBC, standard-of-care chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (PFS). SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received accelerated FDA approval for treatment of pts with mTNBC who have received ≥2 prior therapies for metastatic disease. The confirmatory phase 3 ASCENT study (NCT02574455) in pts with relapsed/refractory mTNBC demonstrated a significant survival benefit of SG over TPC (median PFS: 5.6 vs 1.7 mo, HR 0.41, P&lt; 0.0001; median overall survival [OS]: 12.1 vs 6.7 mo, HR 0.48, P&lt; 0.0001) with a tolerable safety profile. Here we summarize efficacy results for SG vs each TPC agent in ASCENT to examine how each TPC agent performed individually. Methods: Pts had mTNBC refractory to or progressing after ≥2 prior standard chemotherapy regimens. Pts were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8, every 21 days) or single-agent TPC (eribulin, vinorelbine, capecitabine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Secondary endpoints were ORR per RECIST 1.1, duration of response, OS, and safety. Outcomes for each of the agents in the TPC arm were analyzed and compared with SG. Results: Of 529 pts enrolled, 468 were BMNeg. Among pts in the TPC cohort (n = 233), eribulin was the most commonly chosen chemotherapy (n = 126), followed by vinorelbine (n = 47), capecitabine (n = 31), and gemcitabine (n = 29). Treatment with eribulin, vinorelbine, capecitabine, and gemcitabine resulted in shorter median PFS vs SG (2.1, 1.6, 1.6, and 2.7 vs 5.6 mo, respectively); similar results were observed for median OS (6.9, 5.9, 5.2, and 8.4 vs 12.1 mo), ORR (5%, 4%, 6%, and 3% vs 35%), and clinical benefit rate (CBR; 8%, 6%, 10%, and 14% vs 45%). Key grade ≥3 treatment-related adverse events (TRAEs) with TPC overall vs SG included neutropenia (33% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), and anemia (5% vs 8%). Key grade ≥3 TRAEs with eribulin vs SG included neutropenia (30% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), anemia (2% vs 8%), and peripheral neuropathy (2% vs none), respectively. The safety profiles of vinorelbine, capecitabine, and gemcitabine combined were consistent with that of TPC overall and with eribulin. One treatment-related death was reported for the TPC arm (eribulin) and none with SG. Conclusions: The efficacy benefit observed with SG vs TPC in pts with mTNBC was retained when evaluating each TPC chemotherapy agent individually. These results confirm that SG should be considered as a new standard of care in pts with pretreated mTNBC. Clinical trial information: NCT02574455 .

Characterization of BCL-2 alternative proteins and outcome in patients with peripheral T-cell lymphoma (PTCL).

e19531 Background: The outcome of patients with PTCL, NOS is generally very poor, and the identification of biologically rational targets, which may translate into effective and non-toxic treatment strategies, is a high priority. The pro-survival BCL-2 family members BCL-2, BCL-XL (BCL2L1), BCL-W (BCL2L2), BCL2A1 and MCL-1 contribute to tumor maintenance, progression, and chemo-resistance across a range of cancers, but their contributions in PTCL, NOS are poorly understood. Methods: Patients with PTCL, NOS treated between 09/2000 and 09/2019 and with available tissue biopsy were included in the study. Diagnosis was retrospectively confirmed by two expert hematopathologists. BCL-2, BCL-XL, BCL-W, BCL2A1 and MCL-1 expression was assessed by immunohistochemistry (IHC), and the percentage of positive tumor cells assessed by standard microscopy. The 2014 Lugano Classification was used to define response to therapy. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and were compared using log-rank test between patient groups. Results: Twenty-seven patients were included in the study: 67% were male, 52% ≥ 65 year old, and 48% had stage IV disease; 59% were previously treated and 41% received &gt; 2 lines of therapy, including stem cell transplant (SCT) in 19%. The median expression of BCL-2, BCL-XL, BCL-W, BCL2A1 and MCL-1 by IHC was: 30% (range: 0-100%), 10% (range: 0-90%), 100% (range: 40-100%), 20% (range: 0-90%), and 70% (range: 1-100%), respectively. BCL-2A1 was significantly higher in previously treated patients (35% vs 5%, p = 0.02), and in those who had previously received &gt; 2 lines of therapy (40% vs 5%, p = 0.02). Twenty-four (89%) patients were treated after tissue biopsy, 17 (63%) with chemotherapy, 7 (26%) with biological therapy, and 6 (22%) received subsequent SCT. Five (24%) patients achieved complete remission (CR); only BCL-W associated with response, a higher expression (quartiles 3 and 4) being observed among patients not achieving CR (median 100% vs 90%, p = 0.07). After a median follow-up of 28 months (95% CI, 14-42 months), 22 (81%) patients progressed or died, and median PFS was 4 months (95% CI, 2-6 months); only BCL-W associated with PFS, a shorter median PFS being observed for patients with higher expression (3 months vs 7 months, p = 0.001). At most recent follow-up, 17 (63%) patients died, and median OS was 6 months (95% CI, 1-12 months). only BCL-W associated with OS, a shorter median OS being observed for patients with higher expression (4 months vs not reached, p = 0.004). Conclusions: High expression of BCL-W associates with significantly worse outcome in patients with PTCL, NOS. While clinical trials investigating the safety and efficacy of BCL-2 inhibition in PTCL, NOS are ongoing, these results suggest that concomitant BCL-W inhibition may be beneficial, and functional studies aimed at confirming these findings are highly needed.

Clinical outcomes in patients relapsed/refractory after ≥ 2 prior lines of therapy for follicular lymphoma: A systematic literature review and meta-analysis.

e19548 Background: Patients with follicular lymphoma (FL) can have high response rates to early lines of treatment. However, among FL patients relapsed/refractory (r/r) after ≥2 prior lines of therapies (LOT), remission tends to be shorter and there is limited treatment guidance. This study sought to evaluate the clinical outcomes for r/r FL after ≥2 prior LOT using currently available treatment options. Methods: Electronic databases were searched on June 2, 2020. Eligible studies were comparative or non-comparative interventional or observational studies of systemic therapies among adults with FL r/r after ≥2 prior LOT. Prior LOT must have included anti-CD20 monoclonal antibodies and alkylating agents, in combination or separately. Overall response rate (ORR) and complete response (CR) were analyzed using inverse-variance weighting with Freeman-Tukey double-arcsine transformations. Kaplan-Meier (KM) analysis for progression-free survival (PFS) and overall survival (OS) were conducted using digitized curves and the Guyot algorithm. Survival analyses were stratified by ≥2 prior LOT and ≥3 prior LOT groups and were restricted to the observational cohorts as a sensitivity analysis. Results: The meta-analysis included 12 studies published from 2014-2020. Sample size for response outcomes was 340, for survival outcomes with ≥2 prior LOT was 1024 and for ≥3 prior LOT was 502. The estimated ORR in the ≥2 prior LOT group was 56.0% (95% confidence interval [CI]: 47.2 – 64.5) and proportion of patients with CR was 12.2% (95% CI: 8.0 – 17.3). The median OS was 54.4 months (95% CI: 45.8 – 76.0) and median PFS was 10.3 months (95% CI: 9.3 – 11.1). The 24-month OS decreased from 66% in the ≥2 prior LOT group to 60% in the ≥3 prior LOT group (Table 1), with a similar trend in PFS at 24-month (28% vs 24%). Conclusions: This study found that few r/r FL patients with ≥2 prior LOT achieve CR, and despite some benefit, approximately 1/3 of patients die within 24 months. The shorter median PFS with increasing prior LOT suggest treatment durability is suboptimal in later LOT. These findings indicate that patients are underserved by current treatments, demonstrating a need for new treatments that can achieve high rates of response that are durable in this disease.[Table: see text]

Systematic literature review of the real-world burden and use of chemotherapies for treatment of advanced or recurrent endometrial carcinoma.

e17571 Background: Women diagnosed with advanced or recurrent endometrial cancer (EC) have a poor prognosis, with a 5-year survival of only 15% to 17%. While a multi-modality approach is often used for newly diagnosed EC including platinum-based chemotherapy, there are no definitively approved standard treatment options for advanced or recurrent EC following prior systemic therapy (FPST). The real-world evidence surrounding the effectiveness of chemotherapies in this setting is not well characterized. We conducted a systematic literature review to attempt to fill this evidence gap. Methods: Systematic searches were run in Embase, MEDLINE, and the Cochrane Library to identify English-language publications from January 2000 to July 2020. Additional hand searches of 5 key conferences held from 2018 to 2020 were also conducted. The review included observational studies reporting the clinical effectiveness, safety, or treatment patterns of pharmacological treatments in adult women with advanced or recurrent EC. Results: Seventy-seven observational studies met the inclusion criteria, of these 63 studies reported on the effectiveness of chemotherapies. While 57 studies described adjuvant chemotherapy use, 6 described use of chemotherapies FPST, including 1 study in the second line or later. Only one of these 6 studies reported a sample size greater than 100 patients. Chemotherapy FPST included paclitaxel/carboplatin (3 studies), doxorubicin (2 studies), etoposide (1 study), or any platinum-based chemotherapy (1 study). Shorter median overall survival (OS) was observed in patients with treatment-free intervals (TFI) &lt; 6 months from prior systemic therapy (5.5-11.3 months; 2 studies) compared to those with TFI &gt; 6 months (13.0-27.0 months; 3 studies). Similarly, shorter median progression-free survival (PFS) was seen in patients with TFI &lt; 6 months from prior systemic therapy (2.0-3.2 months; 2 studies) vs. those with TFI &gt; 6 months (6.0-10.0 months; 3 studies). Conclusions: Women with advanced or recurrent EC have poor OS and PFS with current chemotherapy regimens, especially for those with TFI &lt; 6 months. The time at recurrence from prior systemic therapy seems to correlate with the outcomes of subsequent treatment. Novel efficacious treatment strategies are required to improve patients’ outcomes in the FPST setting. While extensive real-world evidence exists for patients with EC receiving adjuvant chemotherapy, real world data is limited for use of chemotherapy in advanced or recurrent setting, warranting further research in larger samples of patients.

Hyper engorged cancer associated macrophage-like cells in circulation predict for multi-organ metastatic disease in solid tumors.

3039 Background: Patients with multiple organ metastases have poorer prognoses than those with a single organ metastasis, are frequently associated with drug resistance, and have higher tumor burden. Engorged (≥50um) Cancer Associated Macrophage-Like Cells (CAMLs) are a circulating stromal cell subtype detected in the blood of patients with solid tumors at high risk for recurrence or progression. While numerous studies have shown that ≥50um CAMLs predict poor clinical outcomes, meta-analysis of these studies have also suggested that hyper engorged CAMLs ≥100um (heCAMLs) may be associated with multifocal metastatic disease and even worse outcomes. In this prospective study, we evaluated the presence of heCAMLs in patients with metastatic disease and demonstrated a strong relationship with multi organ spread, which also correlated with shorter Progression Free Survival (PFS) and Overall Survival (OS). Methods: We prospectively recruited 151 patients with metastatic (m) mbreast (n = 58), mlung (n = 34), mprostate (n = 39), and mrenal (n = 20) cancers. Peripheral blood was collected prior to the induction of new treatment for metastatic cancer. Cells were isolated following standard CellSieve techniques, then imaged and measured in ZenBlue. Multi organ metastasis was defined as spread to ≥2 distant organ sites, or any spread to the brain. Single factor ANOVA was conducted to compare heCAML presence in multi organ metastatic patients versus patients with single organ site metastasis. Univariate and multivariate analysis was run to evaluate for PFS and OS against heCAMLs, and all known clinical parameters. Results: 150 viable samples (excluding 1 failed sample) were obtained. Multi organ metastases were present in 55% (n = 83/150) of patients. heCAMLs were found in 59% (n = 49/83) of the multi organ metastatic population, but only in 16% (n = 11/67) of the single site metastatic cohort (p &lt; 0.001). heCAML presence appeared to differentiate multi organ vs single organ metastases in mbreast (85% vs. 52%, p = 0.006), mlung (71% vs. 26%, p = 0.025), mprostate (75% vs. 37%, p = 0.029), and mRCC (88% vs. 36%, p = 0.025). Further, in all n = 150 patients, heCAML presence predicted a significantly shorter median PFS of 4.5 versus 7.2 months, 24 month PFS (HR = 1.67, 95%CI = 1.13-2.45, p = 0.013), and significantly shorter median OS of 13.1 versus 20.4 months, 24 month OS (HR = 2.05, 95%CI = 1.24-3.39, p = 0.008). Conclusions: We examined a non-invasive prognostic blood based assay to determine its relationship to multi organ metastatic spread as well as its prognostic value in several solid cancers. These results showed patients with heCAMLs had higher rates of multi organ metastases, and appear to predict for shorter PFS and OS. Studies of larger cohorts are needed for prospective validation of these initial findings.

Prognostic Utility of Prechemoradiotherapy Albumin-to-Alkaline Phosphatase Ratio in Unresectable Locally Advanced Pancreatic Carcinoma Patients.

Background We investigated the prognostic usefulness of prechemoradiotherapy (CRT) albumin-to-alkaline phosphatase ratio (AAPR) in unresectable locally advanced pancreatic adenocarcinoma (LAPAC) patients managed with definitive concurrent CRT (CCRT). Methods A sum of 136 LAPAC patients who consecutively underwent definitive CCRT was retrospectively analyzed. The AAPR (serum albumin (g/dL)/serum alkaline phosphatase (IU/L)) was calculated by using the parameters obtained from the routine biochemistry tests on the first day of the CCRT. Ideal AAPR cutoff was sought by utilizing receiver operating characteristic (ROC) curve analysis. The primary and secondary endpoints were the impact of the AAPR on the overall survival (OS) and progression-free survival (PFS) results, respectively. Results At a median follow-up of 14.8 months (range: 3.2-85.7), the median PFS and OS times were 7.5 (95% confidence interval (CI): 6.0-9.0) and 14.9 months (95% CI: 11.9-17.9), respectively. The ideal common AAPR cutoff was identified at the rounded 0.46 (area under the curve: 72.3%; sensitivity: 71.2%; specificity: 70.3%) point that dichotomized the patients into two groups: low AAPR (L-AAPR; N = 71) and high AAPR (H-AAPR; N = 65) groups, respectively. Comparative survival analyses showed that the L-AAPR cohort had significantly shorter median PFS (6.8 (95% CI: 5.7-7.9) versus 11.3 (95% CI: 9.9-12.7) months; P = 0.005) and OS (12.8 (95% CI: 10.6-15.0) versus 19.2 (95% CI: 16.9-21.5) months; P = 0.001) durations than their H-AAPR counterparts, separately. Albeit the N1-2 (P = 0.004) and CA 19‐9 > 90 U/mL (P = 0.008) were also found to be associated with inferior outcomes, yet the results of the multivariate analyses ascertained the L-AAPR as an independent indicator of diminished PFS (P = 0.003) and OS (P = 0.002) results. Conclusion The present results proposed that the pretreatment AAPR < 0.46 was a novel independent indicator of adverse PFS and OS in unresectable LAPAC patients undergoing definitive CCRT.

A Low Total Psoas Muscle Area Index Is a Strong Prognostic Factor in Metastatic Pancreatic Cancer.

The total psoas area index (TPI) is an emerging alternative to the total skeletal muscle area index as a prognostic factor but has never been evaluated in metastatic pancreatic cancer (mPC). Areas were manually recorded, as previously described. Sex-specific cutoffs were identified by optimum stratification of TPI using log-rank χ2 statistic associated with mortality to define sarcopenic psoas. Progression-free survival (PFS) and overall survival (OS) were the primary objectives. Two period groups were used as internal validation. During the period study, 79 patients were treated for mPC. The TPI was correlated with PFS (hazards ratio, 0.81; P = 0.02) and OS (hazards ratio, 0.7; P < 0.001). Optimum thresholds defining sarcopenic psoas were less than 5.73 cm2/m2 in men and less than 4.37 cm2/m2 in women. Patients with sarcopenic psoas (62.0%) had shorter median PFS (2.9 months) compared with the others (6.6 months, adjusted P log-rank = 0.01), independently to the intensity of chemotherapy, weight loss, and performance status greater than 1. Similarly, OS was independently shorter in patients with sarcopenic psoas (7.6 months) versus the others (22.2 months, adjusted P < 0.001). These results were confirmed in the 2 period groups. A low TPI is a stronger independent prognostic factor in mPC.

Molecular Profiling of Metastatic Bladder Cancer Early-Phase Clinical Trial Participants Predicts Patient Outcomes.

Prognosis for patients with metastatic bladder carcinoma (mBC) remains limited and in need of novel therapies. We retrospectively analyzed medical records of 43 patients with platinum-refractory metastatic bladder cancer (mBC) who participated in one or more phase I trials of various investigational therapies. Patients' tumors or circulating tumor DNA were analyzed by next-generation sequencing. The median progression-free survival was 4.2 months, the median overall survival was 9.6 months, and the overall response rate was 17.5%. TP53, ERBB2, PI3KCA, FGFR3, and ARID1A alterations were detected in 66%, 29%, 27%, 24%, and 22% of all patients, respectively. Alterations in FGFR3 were almost mutually exclusive of TP53. More than half (64%) of patients with an FGFR alt received an FGFR inhibitor, 67% of which achieved disease control. Among patients with urothelial carcinoma histology, those harboring a TP53 alteration had a shorter median progression-free survival (PFS) compared with those whose tumors carry wild-type TP53. The reverse relationship was observed in patients harboring an FGFR alteration. IMPLICATIONS: Patients with platinum-refractory mBC derive clinical benefit from participating in early-phase clinical trials and their survival outcomes correlate with the genetic profile of the tumor. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/3/395/F1.large.jpg.

Abstract PS2-19: Circulating tumor cell (CTC) enumeration in a phase II trial of pazopanib in addition to endocrine therapy in patients with hormone resistant advanced breast cancer (ABC)

Abstract Background: CTCs are detectable in approximately 50% of pts with metastatic breast cancer, and elevated CTC levels are an independent negative prognostic factor. CTCs have been shown to play a valuable role in predicting outcomes in pts with ABC treated with chemotherapy or endocrine therapy. This phase II trial was conducted to evaluate the clinical benefit (CB) of pazopanib, a VEGF receptor tyrosine kinase inhibitor (TKI) combined with nonsteroidal aromatase inhibitors (NSAIs) in pts with ABC resistant to NSAIs. As an exploratory analysis, we hypothesized that CTC levels might be correlated with response to pazopanib plus endocrine therapy. Methods: Eligibility included postmenopausal women with hormone receptor positive (HR+) ABC and progressive disease after at least one month of NSAIs. Treatment was pazopanib 800 mg/day plus either letrozole or anastrozole. The primary endpoint was clinical benefit rate at 12 weeks (CBR12, wks). Secondary endpoints included progression free survival (PFS), safety, and the impact of pazopanib and NSAI on CTCs. A CBR of 20% was considered a clinically meaningful comparison to the expected CBR of &amp;lt;5% with continued NSAIs after PD. Blood samples were collected for CTC analysis at baseline, then every 4 wks while on treatment. The presence of CTCs was assessed using the FDA-cleared CellSearch System; CTCs were defined as EPCAM-positive, CD45-negative nucleated cells. Samples with 5 CTCs per 7.5 mLs of blood were considered CTC-positive. Results: 32 pts were enrolled; 28 are evaluable for study endpoints. The median age was 58 years (range: 41-77). Pts were heavily pre-treated, with a median of 2 prior hormone therapies (range 1-6) and 1 prior chemotherapy (range 0-8). 8 pts (28.6%) stopped treatment due to adverse events, and 6 pts progressed before wk 12. CBR12 was 46.4% (12 SD, 1 PR), and CBR24 was 25% (5 SD, 2 PR). Safety has been presented (ASCO 2020). Median PFS was 20 wks, and median PFS for pts with CBR12 was 24 wks. Five (22%) of 23 pts with CTC data were CTC-positive (5 CTC/7.5 mL). There was no significant association between CBR12 and CTC status at baseline, or between CBR12 and change in CTC status (baseline to 4 wks after initiation of treatment). 7 pts had non-CBR12 and CTC data; 4 pts (n=4/7; 57%) were CTC positive at either baseline, week 4 or both. 11 pts had CBR12 and CTC data; all patients were CTC negative at baseline and remained negative at 4 wks. 7 pts had PFS &amp;gt;6 months (24, 32, 36, 36, 48, 184 and 274 wks), and 6 had CTC data: all were CTC-negative at baseline and 4 wks, then remained negative at 12 wks. Based on baseline values only, CTC-positive pts had a shorter median PFS compared to CTC-negative pts, but the difference was not statistically significant (11 wks vs 14 wks, p=0.18). Persistently CTC negative patients had significantly longer PFS compared to patients who were CTC positive at any time during study treatment (36 wks vs 11 wks, p=0.01). Conclusions: The addition of pazopanib to NSAIs resulted in a CBR12 of 46.4%, and a CBR24 of 25% in pts with heavily pre-treated ABC resistant to NSAIs. These results support clinical efficacy of antiangiogenic TKI in HR+ ABC and suggest benefit in hormone resistant disease. Consistently negative CTCs correlated with response and response duration. PFS was significantly longer in patients who were consistently CTC negative, further defining the prognostic role of CTCs in HR+ ABC. (NCT01466972) Citation Format: Ozge Gumusay, Mark Jesus M. Magbanua, Melanie C. Majure, Travis Deal, Jonathan R. Renslo, Chiara A. Wabl, Michelle E. Melisko, A. Jo Chien, Andrei Goga, Mark M. Moasser, John W. Park, Jimmy Hwang, Hope S. Rugo. Circulating tumor cell (CTC) enumeration in a phase II trial of pazopanib in addition to endocrine therapy in patients with hormone resistant advanced breast cancer (ABC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-19.