Cooperative Oncology Group Performance Research Articles

Real-world analysis of use of lenvatinib in differentiated thyroid cancers.

e18075 Background: Lenvatinib is one of the approved treatments for radioiodine refractory differentiated thyroid cancers. However, there is very limited data from India on real-world efficacy and adverse events of Lenvatinib and hence this analysis was performed. Methods: This was a retrospective analysis in which patients of radioiodine refractory differentiated thyroid cancer as per the select study criteria who received lenvatinib were selected for the study over the last 4 years. The baseline demographic characteristics, adverse events of lenvatinib, the date of progression and the date of overall survival (OS) were extracted from the electronic medical records (EMR) of the Tata Memorial Hospital. SPSS version 20 was used for analysis. Results: Thirty patients were identified. The median age was 54.5 years (25-77). The male: female ratio was1:1. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0-1 in 21(70%), 2 in 4(13.3%) and 3 in 5(16.7%). The thyroid status was hypothyroid in 10 patients (33.3%), euthyroid in 12(40%) and hyperthyroid in 8(26.7%). In 5 patients it had to be stopped because of toxicity, these were proteinuria in 2, a hand-foot syndrome in 2 and diarrhoea in 1. The response rate was 56.7% (n = 17). The median progression-free survival (PFS) on lenvatinib was 366 days(95%CI 170.3-561.67) and the 2 year PFS was 29.3% (standard error 12.1) The median overall survival (OS) on lenvatinib was 411 days (95%CI 95.5-726.6). The 2 year OS was 38.8% (standard error -12.5%) and 5 year OS was 14.6% (standard error 12.1). Conclusions: In the real world lenvatinib provides a 2 year PFS and OS of 29.3% and 38.8% which is lower than that reported in the pivotal SELECT study.

Evaluating the impact of performance status criteria on minority eligibility for oncology clinical trials.

e18701 Background: Restrictive criteria contribute to low enrollment in clinical trials. These criteria can also amplify health disparities by reducing the racial and ethnic diversity of the cohort. Many studies show that minority patients exhibit worse Eastern Cooperative Oncology Group (ECOG) performance status than white patients. Based on clinical trial data, some researchers have hypothesized that relaxing the ECOG criterion in clinical trial criteria could improve the diversity of the cohort. However, little research exists to measure ECOG’s impact on minority eligibility. Using Real-World Data (RWD), we evaluate whether relaxing the ECOG criterion monotonically increases the racial diversity of the cohort in oncology clinical trials. Methods: We used ConcertAI’s database of US oncology Electronic Medical Record (EMR) data, which includes clinical data from CancerLinQ Discovery™. We conducted sensitivity analyses for the inclusion criteria of 16 different clinical trials across multiple cancer indications. For each trial, we created five cohorts based on five different ECOG score upper limits. For example, the first cohort only included patients who had an ECOG of 0, the second cohort included patients with an ECOG of 0 or 1, etc. We then recorded the percentage of non-white patients for the resulting cohorts. We ran simple linear regressions to measure whether the change in the percentage of non-white patients was statistically significant. Results: Relaxation in ECOG status led to no uniform change in the racial diversity of patients across the 16 trials. The limited changes we did observe were not statistically significant. Conclusions: Our findings suggest that improving diversity will require more than just relaxing ECOG restrictions, and a multi-faceted approach may be needed. Future research exploring the relationship between ECOG and diversity should control for potential confounders like age, gender, and comorbidities using multivariable models. Such research needs to also account for patients with unknown race and ECOG, which represented large parts of our study population. Such research could elucidate whether the phenomenon observed in the general population—that minority patients tend to have worse performance status than whites—holds true in the sub-population of oncology patients.[Table: see text]

Epidemiological and demographic characteristics of gynecological sarcoma: Results of the prospective intergroup registry for gynecological sarcoma in Germany (REGSA–NOGGO RU1).

e17630 Background: Gynecological sarcomas (GS) are orphan diseases associated with poor prognosis. With the aim to improve our understanding of GS, the German registry for gynecological sarcoma (REGSA) prospectively recorded patients’ data with GS treated in real-life clinical practice at initial diagnosis and the time of relapse. Herein, we present the analysis of demographic and epidemiological data of patients with GS at the time of initial diagnosis. Methods: An exploratory analysis among different histological subtypes of GS was performed and patients’ data were compared to data of the healthy standard population. We analyzed the following variables: age, body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, ethnicity, lifestyle habits, pregnancies, and comorbidities. Results: Data of 389 patients with GS were descriptively evaluated. Leiomyosarcoma (LMS) was the most common histological subtype (47.3%), followed by low-grade endometrial stromal sarcoma (LG-ESS; 17.7%), high-grade ESS (HG-ESS; 10.4%), adenosarcoma (AS; 9.1%) and undifferentiated uterine sarcoma (UUS; 6.2%). Overall, 9.4% of all GS were classified as “other” rarer histological subtypes. The mean age of patients was 57.4 years. The youngest were the patients with LG-ESS (54.3 years), whereas patients with AS were the oldest ones (61.7 years). There were no statistically significant differences in average age nor in BMI among patients with different histological subtypes of GS. In contrast, compared to the standard population, the BMI of patients with GS was significantly higher (27.5 kg/m² vs 25.1 kg/m², p< 0.001). Overall, 70.7% of all patients with LMS had FIGO stage I or II. Therefore, it is not surprising that most of patients had ECOG performance status 0 (68.3%). According to the countries of recruitment (i.e. Germany, Austria, Switzerland), 92.8% of patients were Caucasian. REGSA patients were less likely to be smokers compared to the national average of German women (13.4% vs 18.6%). One or two births per patient were reported in 58.2% of patients. In comparison the current birth ratio in Germany is approximately 1.5 children per woman. Hypertension was the most common comorbidity as observed in 33.2% of all cases, followed by thyroid diseases (18.6%). The prevalence of hypertension in the German female standard population is approximately 30% and approximately every third person will be affected by thyroid diseases in their lifetime. Conclusions: REGSA data showed no statistically significant differences in terms of demographic variables between different histological subtypes of GS, whereas statistically significant difference such as BMI was identified as compared to the standard population. Further research is needed to specify risk factors of GS in order to promote primary prevention of this fatal disease.

Real-world analysis of BRAF inhibitors with patients positive for BRAF V600E mutations diagnosed with rare tumors.

e15085 Background: BRAF mutation is seen in multiple cancers and BRAF inhibitors have a tumor agnostic nature. However there is very limited real world data for BRAF inhibitors and hence we have performed this analysis. Methods: In Tata Memorial Hospital, the medical oncology solid unit 2 maintains a prospective database of all patients who undergo molecular testing. A query was raised from this database and 17 patients were identified who were BRAF mutant positive. The demographic details of these patients, the previous treatment details, the therapy received by these patients, the response to the therapy, the date of progression and the date of death was recorded. Descriptive statistics were performed and Kaplan-Meier analysis was used to estimate the progression-free survival (PFS) and overall survival (OS). Results: In all the 17 patients the mutation was BRAF V600E.The median age of the patients was 58 years (16-77). The m:f ratio was 13:4. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0-1 in 9 patients (52.9%) and 2-3 in 8 patients (47.1%). The primary sites included in the analysis were lung cancer in 8 (47.1), glioma in 3 (17.7), thyroid in 2 (11.8%) and one each of parotid, melanoma, esophagus, thymoma. BRAF inhibitors could be provided in 9 patients (52.9%) and its was dabrafenib-trametinib in 8 patients and vemurafenib then dabrafenib-trametinib in 1 patient. The median progression free survival was 203 days (95% CI 25.1-380.9) and overall survival was 220 days (95% CI 49.8-408.2) . Conclusions: The real world data suggests that the efficacy of BRAF inhibitors seems to be lower than that seen in pivotal studies. The reasons for which is unknown.

Nivolumab with ipilimumab for MSI-H colorectal cancer with liver metastases.

e15556 Background: Immune checkpoint inhibitor (ICI) therapy has recently demonstrated durable clinical benefit in patients with advanced mismatch repair deficient (dMMR) colorectal cancer. The aim of this study was to test the combination of nivolumab and ipilimumab in microsatellite instability-high (MSI-H) colorectal cancer patients with oligometastatic liver disease. Methods: Twelve patients with MSI-H mCRC and one prior line of treatment for metastatic disease received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks until disease progression or discontinuation. The primary endpoint was objective response rate (ORR). Results: At baseline, the patients’ median age was 58 years (range, 51-67 years), and 40.7 % of patients were women. Sites of metastases included liver (89.8%), distant lymph nodes (43.6%), and lungs (9.2%). For all 12 patients (median follow-up was 8.2 months), ORR was 71% (95% CI 46.3–78.6). Of 12 patients enrolled, 4 patients (33%) achieved a partial response, and 5 patients (41%) achieved stable disease. Responses were consistent with the overall population across subgroups including age, Eastern Cooperative Oncology Group (ECOG) performance status, prior adjuvant/neoadjuvant therapy, and mutation status. Two patients (16%) had grade 3–4 treatment-related adverse events. Conclusions: Nivolumab plus ipilimumab demonstrated significant clinical benefit and was well tolerated in patients with MSI-H mCRC. Clinical evaluation of ICIs in first-line metastatic, adjuvant and neoadjuvant settings and in combination with other therapies are ongoing.

Efficacy of Gemcitabine in recurrent meningioma: A phase II study.

e14044 Background: Systemic therapy has a limited role in meningiomas. There is in-vivo and in-vitro data that gemcitabine can potentially be useful in meningiomas. We did a phase II study with the primary objective of studying the 6-month progression-free survival (PFS) of gemcitabine in meningiomas. Methods: This was a single-arm prospective phase II study. Adult patients with recurrent meningiomas who were not eligible for local therapies with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 with normal organ and marrow function were included in this study. Patients who had received any chemotherapy within the last three weeks or on any other investigational agents were excluded. All patients received gemcitabine 1000 mg/m2 administered intravenously over 30 minutes on day 1, day 8 and day 15 every 4 weeks until disease progression or development of intolerable side effects. The response was assessed as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. The adverse events were recorded as per the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The primary objective of this study was to assess the 6-months progression-free survival (PFS). The 6-months progression-free survival (PFS) of 50% or more was considered sufficient to warrant further studies. Results: Nine patients were recruited in this study. The median age of the patient was 56 years(24-73). The m: f ratio was 2:3. All patients had undergone previous surgeries and 8 patients had undergone previous radiotherapy. The median number of cycles of gemcitabine was 3. Any grade toxicity was observed in all patients. Grade 3 and above adverse events were not observed. The two commonest adverse events noted were anaemia in 7 (77.8%) patients and vomiting in 2 (22.2) patients. The best response was stable disease (SD) in 3 patients (33.4%) and progressive disease (PD) in 6 (66.6%) patients. At a median follow up of 18.8 months, the 6-months progression-free survival (PFS) was 33.3% (95%CI 7.8-62.3). The 1-year overall survival (OS) was 66.7 % (95%CI 28.2-87.8). Conclusions: Gemcitabine failed to meet the prespecified endpoint of 6-month PFS and does not warrant any further investigation in this setting. Clinical trial information: CTRI/2019/02/017499.

ALTER-UC-001: Phase II trial of anlotinib plus everolimus as first-line treatment for advanced non–clear cell renal cell carcinoma.

TPS4598 Background: For patients (pts) with recurrent or stage IV non-clear cell renal cancer (nccRCC), the medical treatment guidelines recommend the first choice to participate in clinical trials, or use TKI drugs such as sunitinib, and mTOR inhibitors such as everolimus. Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI). It’s antitumor targets include vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-kit. This a single-center, single-arm, phase II trial which will evaluate the efficacy and tolerability of anlotinib hydrochloride plus everolimus as first-line therapy in pts with nccRCC (NCT05124431). Methods: Key inclusion criteria are: age ≥18 years; histologically confirmed advanced nccRCC, advanced disease is defined as TNM stage IV, not available for surgery, locally recurrent or metastatic renal cell carcinoma; no prior systemic drug therapy for advanced disease; Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Approximately 30 pts will be assigned to receive anlotinib hydrochloride: 12 mg every 21 days (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) by oral, and everolimus 5mg qd, continued for up to 1 year (∼17 cycles ) or until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR). Radiographic imaging will be performed every 6 weeks. Secondary endpoints included overall disease control rate (DCR), progression free survival (PFS), and over survival (OS). Adverse events will be monitored throughout the study and graded according to CTCAE V5.0. Recruitment have begun in Jan. 2022. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Clinical trial information: NCT05124431.

Twice-daily thoracic radiotherapy for patients with locally advanced or oligometastatic non-small cell lung cancer: A single-center observational study.

e21070 Background: Radiotherapy is standard treatment for locally advanced or oligometastatic non-small cell lung cancer (NSCLC). Once-daily thoracic radiotherapy of 60～66 Gy in 30～33 fractions is considered to be the most effective schedule in the past. The aim of this study was to investigate whether twice-daily thoracic radiotherapy improves survival and reduces toxicity. Methods: Patients aged 18 years and older with treatment-naive confirmed locally advanced or oligometastatic NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1 were eligible. Participants received thoracic radiotherapy of 40～80 Gy(2～4Gy/fraction, bid) and 30～60 Gy (1.5～2.0Gy/fraction, bid) to the primary lung tumour and positive lymph node metastases respectively. Patients received 2-4 cycles of chemotherapy or oral targeted drugs if the driver genes is positive. Results: In total, 124 patients were included in this study between February 2016 to March 2020. The median patient age was 61 years old and 113(91.1%) patients were male. The patient group included 72 patients with stage IIB～IIIC, and 52 patients with stage IV disease. Histological diagnosis was squamous cell carcinoma in 68 patients, adenocarcinoma in 56 patients. Median follow-up was 24.8 months (range 1.5-59.7months). The 1, 2, 3-year OS were 83.1% and 70.6%, 60.6%, respectively. The incidence of ≥Grade 2 radiation pneumonitis and esophagitis were was 25.6% and 15.2%, respectively. The most common grade 3-4 adverse events were leukopenia (17 [13.7%]), thrombocytopenia (5 [4.0%]), anaemia (15[12.0%]) and lymphopenia (30[24.2%]). None of the patients experienced fatal bronchopulmonary hemorrhage or tracheal fistula. Conclusions: Twice-daily thoracic radiotherapy is feasible and well tolerated for locally advanced or oligometastatic NSCLC. It needs to be further confirmed by large randomized controlled clinical studies. Clinical trial information: ChiCTR2100055096.

Leptomeningeal carcinomatosis: Retrospective review of a large series.

e14005 Background: Leptomeningeal carcinomatosis (LMC) remains associated with a poor outcome and effective treatment options are not currently available. Knowledge about risk factors, diagnosis and optimal treatment of LMC is still limited. Methods: We performed a retrospective analysis of all consecutive patients with a solid tumor and LMC confirmed by CSF (cerebrospinal fluid)-positive cytology, diagnosed at our institution between January 2013 and November 2020. Clinical, imaging and cytologic data were collected. We used multivariable Cox regression models adjusted for age and Eastern Cooperative Oncology Group (ECOG) performance status to test the prognostic impact of clinical and treatment-related variables. Results: A total of 73 patients with LMC were identified, 75% female. The most common cancers were breast (51%, n = 37), lung (22%, n = 16), and melanoma (11%, n = 8). Most patients presented with intracranial hypertension (58%, n = 42), followed by cerebellar symptoms (20%, n = 15), radiculopathy (19%, n = 14), cranial nerve palsies (16%, n = 12), seizures (12%, n = 9), and other (4%, n = 3). More than half of patients (56%) had evidence of leptomeningeal involvement only, while 25% of patients (n = 18) had known central nervous system (CNS) metastases and 19% (n = 14) were diagnosed simultaneously with CNS metastases. Median time from primary tumor diagnosis to LMC was 32 months. Median overall survival (mOS) was 1.57 months (95% CI 1.17-2.32 months), with 15% of patients alive at 6 months (95% CI 9-26%). Patients with gynecological (7%, n = 5) and lung cancer had the best mOS (67 and 64 days, respectively), and patients with melanoma had the worst mOS (18 days). mOS in patients with evidence of meningeal involvement by MRI was 41 days, compared to 71.5 days in patients with a negative MRI. Starting a new systemic treatment was associated with a better prognosis (survival hazard ratio (HR) 0.39, 95% CI 0.21-0.75, p = 0.004). Forty patients (55%) received specific treatment for LMC. Neither intrathecal treatment nor radiation were associated with an improved outcome (HR 1.03, 95% CI 0.51-2.10, p = 0.930 and HR 0.60, 95% CI 0.30-1.17, p = 0.130, respectively). Presenting with seizures was significantly associated with a worse prognosis (HR 3.23, 95% CI 1.35-7.76, p = 0.009). In CSF cytology, both pleocytosis (> 5 cells/mm3) and hyperproteinorhachia were individually associated with a worse prognosis (pleocytosis: HR 1.94, 95% CI 1.16-3.26, p = 0.012; hyperproteinorhachia: HR 2.61, 95% CI 1.28-5.32, p = 0.008). Conclusions: In this large series of patients diagnosed with LMC based on positive CSF cytology, the outcome was poor. Absence of leptomeningeal involvement by MRI and switching to a new treatment regimen were associated with a better outcome, likely reflecting tumor burden and patient selection. LMC will likely become more common as systemic treatment options and imaging improve and effective treatment options are an urgent and yet unmet need.

Phase 1 study of JNJ-69086420, an actinium-225-labeled antibody targeting human kallikrein-2, for advanced prostate cancer.

TPS5104 Background: Radioligand therapy for metastatic castration resistant prostate cancer (mCRPC) has been shown to prolong survival, delay disease progression, and improve quality of life, raising hopes that these gains will be amplified with even more cancer-specific targets and more powerful radioligands. Human kallikrein-related peptidase 2 (hK2) is a tumor-associated member of the kallikrein family that shares significant homology to prostate-specific antigen and is minimally expressed in normal non-prostate tissues. JNJ-69086420 (JNJ-420; 225Ac-DOTA-h11B6 [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]), is a first-in-class radioimmunotherapy targeted to hK2 antigen. In a phase 0 study of [111In]-DOTA-h11B6, patients with mCRPC (progressed on standard therapies), treatment with a single dose of [111In]-DOTA-h11B6 (2 mg) with/without 8 mg h11B6, demonstrated safety, good tumor localization, nominal normal-organ uptake, and no difference in pharmacokinetics (PK) between 2 and 10 mg antibody mass (Morris et al. J Clin Oncol. 2021 39:6 suppl, 122). We have initiated the first-in-human study to assess the safety, PK, pharmacodynamic (PD), and clinical activity of Ac-225 radiolabeled JNJ-420, to determine its recommended phase 2 dose (RP2D) in adults with advanced PC. Methods: This open-label, multicenter, phase 1 study will recruit approximately 50 men (aged ≥18 years) with advanced PC across dose escalation (Part 1) and expansion (Part 2) parts. Key eligibility criteria: mCRPC with histologic confirmation of adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate organ function based on hematology and serum chemistry, and 1 or more prior novel androgen receptor-targeted therapies (prior chemotherapy acceptable). Key exclusion criteria: prior treatment with radium/strontium/samarium/radioconjugate therapy, superscan findings as protocol defined, active central nervous system metastases. In Part 1, men will receive intravenous (IV) injection of 50 μCi/ 2 mg JNJ-420 (once every 8 weeks) with one or multiple doses; escalation of dose levels to be based on dose limiting toxicities (DLTs) evaluation, until RP2D identification. In Part 2, JNJ-420 is to be given at one of the RP2D(s) determined in Part 1. Primary endpoint is safety (incidence and severity [grading per NCI-CTCAE V5.0] of AEs including DLTs). Secondary endpoints include prostate specific antigen response rate, overall response rate (PCWG3 modified RECIST 1.1 criteria), PK, PD, immunogenicity, and biomarker analyses. Enrollment began in Dec 2020; as of 10 Feb 2022, 4 sites have been initiated and 23 patients enrolled; currently, dose escalation is ongoing. Clinical trial information: NCT04644770.

Survival outcomes for dostarlimab and real-world (RW) treatment (tx) paradigms in post-platinum patients (pts) with advanced/recurrent (A/R) endometrial cancer (EC): The GARNET trial versus an external control arm from the Flatiron Health database.

5593 Background: There are limited treatment options for pts with A/R EC progressing on or after platinum-based chemotherapy (PBCT) and their prognosis is poor. This study compared the efficacy of the anti-programmed death (PD)-1 antibody dostarlimab evaluated in the single-arm, Phase I GARNET trial with current RW tx. Overall survival (OS) of pts with A/R mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) EC receiving dostarlimab in Cohort A1 of the GARNET trial was compared with an equivalent RW cohort receiving non-anti-PD-(ligand [L])1 tx. Methods: The dostarlimab arm was the GARNET (Cohort A1) dMMR/MSI-H EC safety population. For the external control arm, a RW cohort was constructed using the Flatiron Health database and aligning eligibility criteria with those for GARNET, including pts with A/R EC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1, who had received ≤2 lines of chemotherapy (≥1 line PBCT) and no anti-PD-(L)1 therapy. GARNET pts who received anti-PD-(L)1 therapy following dostarlimab (n=5/129) were excluded. Inverse probability of tx weighting (IPTW) was performed based on propensity scores constructed from key prognostic factors identified by literature review and clinical experts. With IPTW, Kaplan–Meier curves were created, OS rates estimated, and adjusted hazard ratios (HR) estimated by a Cox regression model. MMR/MSI status, only partially available in Flatiron and considered not significantly prognostic for OS as per a recent meta-analyses, was not included in the IPTW. Results: Baseline characteristics for GARNET (N=124) and RW (N=185) after IPTW are shown in the Table. Dostarlimab was associated with a 44% lower risk of death compared with RW tx (OS HR [95% confidence interval {CI}] 0.56 [0.385–0.812]; p=0.002) (see Tablefor median OS). Survival rates (95% CI) were higher for dostarlimab than RW tx at 12 months (mos) (72% [57%–82%] vs 51% [43%–59%]), 18 mos (57% [41%–70%] vs 40% [32%–48%]), and 24 mos (53% [37%–67%] vs 34% [26%–42%]). Conclusions: These results indicate that pts with A/R EC receiving dostarlimab in the GARNET trial had significantly lower risk of death than those receiving current non-anti-PD-(L)1 tx in the RW.[Table: see text]

Identification and Validation of a Prognostic Prediction Model in Diffuse Large B-Cell Lymphoma

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a heterogeneous group with varied pathophysiological, genetic, and clinical features, accounting for approximately one-third of all lymphoma cases worldwide. Notwithstanding that unprecedented scientific progress has been achieved over the years, the survival of DLBCL patients remains low, emphasizing the need to develop novel prognostic biomarkers for early risk stratification and treatment optimization.MethodIn this study, we screened genes related to the overall survival (OS) of DLBCL patients in datasets GSE117556, GSE10846, and GSE31312 using univariate Cox analysis. Survival-related genes among the three datasets were screened according to the criteria: hazard ratio (HR) >1 or <1 and p-value <0.01. Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analysis were used to optimize and establish the final gene risk prediction model. The TCGA-NCICCR datasets and our clinical cohort were used to validate the performance of the prediction model. CIBERSORT and ssGSEA algorithms were used to estimate immune scores in the high- and low-risk groups.ResultsWe constructed an eight-gene prognostic signature that could reliably predict the clinical outcome in training, testing, and validation cohorts. Our prognostic signature also performed distinguished areas under the ROC curve in each dataset, respectively. After stratification based on clinical characteristics such as cell-of-origin (COO), age, eastern cooperative oncology group (ECOG) performance status, international prognostic index (IPI), stage, and MYC/BCL2 expression, the difference in OS between the high- and low-risk groups was statistically significant. Next, univariate and multivariate analyses revealed that the risk score model had a significant prediction value. Finally, a nomogram was established to visualize the prediction model. Of note, we found that the low-risk group was enriched with immune cells.ConclusionIn summary, we identified an eight-gene prognostic prediction model that can effectively predict survival outcomes of patients with DLBCL and built a nomogram to visualize the perdition model. We also explored immune alterations between high- and low-risk groups.

Effect Of NESEM™/s2013 In Indian Population Undergoing Conventional Treatment For The Malignancies Of The Head &amp; Neck, Git, Ovary, Breast And Lung As An Adjunct

Effect Of NESEM™/s2013 In Indian Population Undergoing Conventional Treatment For The Malignancies Of The Head &amp; Neck, Git, Ovary, Breast And Lung As An Adjunct

Development and validation of a new risk scoring system for solid tumor patients with suspected infection

This study aimed to develop a new prognostic model for predicting 30-day mortality in solid tumor patients with suspected infection. This study is a retrospective cohort study and was conducted from August 2019 to December 2019 at a single center. Adult active solid tumor patients with suspected infection were enrolled among visitors to the emergency room (ER). Logistic regression analysis was used to identify potential predictors for a new model. A total of 899 patients were included; 450 in the development cohort and 449 in the validation cohort. Six independent variables predicted 30-day mortality: Eastern Cooperative Oncology Group (ECOG) performance status (PS), peripheral oxygen saturation (SpO2), creatinine, bilirubin, C-reactive protein (CRP), and lactate. The C-statistic of the new scoring system was 0.799 in the development cohort and 0.793 in the validation cohort. The C-statistics in the development cohort was significantly higher than those of SOFA [0.723 (95% CI: 0.663–0.783)], qSOFA [0.596 (95% CI: 0.537–0.655)], and SIRS [0.547 (95% CI: 0.483–0.612)]. The discriminative capability of the new cancer-specific risk scoring system was good in solid tumor patients with suspected infection. The new scoring model was superior to SOFA, qSOFA, and SIRS in predicting mortality.

Phase 1 study of JNJ-69086420, an actinium-225-labeled antibody targeting human kallikrein-2, for advanced prostate cancer.

TPS206 Background: Radioligand therapy for metastatic castration resistant prostate cancer (mCRPC) has been shown to prolong survival, delay disease progression, and improve quality of life, raising hopes that these gains will be amplified with even more cancer-specific targets and more powerful radioligands. Human kallikrein-related peptidase 2 (hK2) is a tumor-associated member of the kallikrein family that shares significant homology to prostate-specific antigen and is minimally expressed in normal non-prostate tissues. JNJ-69086420 (JNJ-420; 225Ac-DOTA-h11B6 [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]), is a first-in-class radioimmunotherapy targeted to hK2 antigen. In a phase 0 study of [111In]-DOTA-h11B6, patients (pts) with mCRPC (progressed on standard therapies), treatment with a single dose of [111In]-DOTA-h11B6 (2 mg) with/without 8 mg h11B6, demonstrated safety, good tumor localization, nominal normal-organ uptake, and no difference in PK between 2 and 10 mg antibody mass (Morris et al. J Clin Oncol. 2021 39:6 suppl, 122). We have initiated the first-in-human study to assess the safety, pharmacokinetics (PK), pharmacodynamic (PD), and clinical activity of Ac-225 radiolabeled JNJ-420, to determine its recommended phase 2 dose (RP2D) in adults with advanced PC. Methods: This open-label, multicenter, phase 1 study will recruit approximately 50 men (aged ≥18 years) with advanced PC across dose escalation (Part 1) and expansion (Part 2) parts. Key eligibility criteria: mCRPC with histologic confirmation of adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate organ function based on hematology and serum chemistry, and 1 or more prior novel androgen receptor-targeted therapies (prior chemotherapy acceptable). Key exclusion criteria: prior treatment with radium/strontium/samarium/radioconjugate therapy, superscan findings as protocol defined, active central nervous system metastases. In Part 1, men will receive intravenous (IV) injection of 50 μCi/ 2 mg JNJ-420 (once every 8 weeks) with one or multiple doses; escalation of dose levels to be based on dose limiting toxicities (DLTs) evaluation, until RP2D identification. In Part 2, JNJ-420 is to be given at one of the RP2D(s) determined in Part 1. Primary endpoint is safety (incidence and severity [grading per NCI-CTCAE V5.0] of AEs including DLTs). Secondary endpoints include prostate specific antigen response rate, overall response rate (PCWG3 modified RECIST 1.1 criteria), PK, PD, immunogenicity, and biomarker analyses. Enrollment began in Dec 2020; as of Sep 2021, 4 sites have been initiated and 14 pts enrolled; currently, dose escalation is ongoing. Clinical trial information: NCT04644770.

Abstract PD13-01: Balixafortide (a CXCR4 antagonist)+eribulin versus eribulin alone in patients with HER2 negative, locally recurrent or metastatic breast cancer: An international, randomized, phase 3 trial (FORTRESS)

Abstract Background: Balixafortide (B), a synthetic cyclic peptide, is a potent selective CXCR4 antagonist with high affinity for the human CXCR4 receptor in pre-clinical studies and is currently being investigated in metastatic breast cancer (mBC). Encouraging safety and efficacy data were previously published from a Phase 1 trial investigating B + eribulin (E) in patients (pts) with human epidermal growth factor receptor 2 negative (HER2-) mBC. Methods: In this multicenter, open-label trial, pts were randomized 1:1 to receive B (5.5 mg/kg) + E (1.4 mg/m2) or E alone. Eligible pts had HER2- locally advanced or mBC and had previously received 1−4 lines of chemotherapy in the advanced setting. Pts with hormonal receptor positive (HR+) disease must have received ≥1 line of endocrine therapy. The primary efficacy endpoints included objective response rate (ORR) and progression free survival (PFS) in the ≥3rd line population and PFS in the overall population. Overall survival (OS) was a key secondary endpoint. Results: 432 pts (aged 29-82 years) were enrolled with 348 treated in the ≥3rd line setting. Most pts (66.4%) were treated in the 3rd or 4th line, 96.1% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and 35.6% had triple negative breast cancer. ORR and clinical benefit rate (CBR) data for the ≥3rd line population are presented in the table below. PFS and OS were not improved in the 3rd line population [mPFS 3.5 months (m) vs 4.0 m; hazard ratio 1.07 (96% CI: 0.81, 1.41); interim mOS 11.0 m vs 11.2 m hazard ratio 1.08 (99.9% CI: 0.66, 1.77)]. Results were consistent in the overall population and per investigator assessment.For the overall safety population, serious treatment-emergent adverse events (STEAEs) (28% versus 26.5%), treatment-emergent adverse events (TEAEs) leading to death (6.9% versus 6.4%) and TEAEs ≥Grade 3 (68.3% versus 64.2%) were broadly similar between the two arms. Infusion Related Reactions (IRR) were reported in 43.6% of patients treated with B + E. Conclusions: In this Phase 3 randomized trial, no differences in ORR, CBR, mPFS, or mOS were observed for B + E compared to E alone in any population of HER2-mBC patients. Efficacy parameters for E alone were similar to those reported previously. The combination was B + E was well-tolerated overall. ≥3rd Line Population(N=330)B + E(N=162)E(N=168)Objective Response Rate (95% CI)Per Independent Review Committee13.0% (8.2, 19.1)13.7% (8.9, 19.8)Per Investigator13.6% (8.7, 19.8)13.1% (8.4, 19.2)Clinical Benefit Rate (95% CI)Per Independent Review Committee16.7% (11.3, 23.3)19.6% (13.9, 26.5)Per Investigator21.6% (15.5, 28.7)21.4% (15.5, 28.4) Citation Format: Peter Kaufman, Miguel Martin, Ingrid Mayer, Linda Vahdat, Sonia Pernas, Peter Schmid, Heather McArthur, Rebecca Dent, Hope S Rugo, Carlos Barrios, Alexandra Bobirca, Francois Ringeisen, Daniela Schmitter, Javier Cortes. Balixafortide (a CXCR4 antagonist)+eribulin versus eribulin alone in patients with HER2 negative, locally recurrent or metastatic breast cancer: An international, randomized, phase 3 trial (FORTRESS) [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 PD13-01.

Abstract P2-13-37: A prospective, open, multi-center clinical study of pyrotinib combined with trastuzumab and nab-paclitaxel in neoadjuvant treatment for stage II-III HER2-positive breast cancer patients

Abstract Background: Targeted therapy has significant efficacy in adjuvant and advanced treatment of HER2-positive breast cancer, and it has also promoted its development in neoadjuvant therapy. For HER2-positive breast cancer, chemotherapy with anthracyclines and taxanes combined with trastuzumab targeted therapy is currently the standard regimen for adjuvant or neoadjuvant therapy. On the basis of the preliminary clinical trials, we carried out this study to confirmed efficacy and safety of pyrotinib combined with trastuzumab and nab-paclitaxel as neoadjuvant treatment regimen in patients(pts) with stage II- III HER2-positive breast cancer. Method: In this multicenter, single arm, prospective, open-label phase II study, 46pts with stage II-III HER2-positive breast cancer will be enrolled (in Simon twostages model, 16 pts will be enrolled in the first stage) to receive pyrotinibcombined with trastuzumab and nab-paclitaxel. The inclusion criteria are asflows. (1) female aging from 18 to 75; (2) Eastern Cooperative Oncology Group(ECOG) performance score of 0-1; (3) Life expectancy is no less than 12weeks;(4) Pathologically confirmed HER-2 positive breast cancer;(5) earlystage (T2-3, N0-1, M0) or locally advanced (T2-4, N2, or N3), with tumor sizeno less than 2cm in diameter. All pts will receive pyrotinib (400mg qd) andtrastuzumab: 8 mg/kg for cycle 1 and 6 mg/kg for cycles 2-6, intravenousinfusion, 21 days for 1 cycle, a total of 6 cycles and nab-paclitaxel: 260mg/m2,intravenous infusion, 21 days as a cycle, a total of 6 cycles. The primaryendpoint is pathological complete response rate (pCR: ypT0/is, ypN0), and thesecondary endpoints are disease-free survival time (DFS), objective responserate (ORR), and survival time without distant metastasis (DDFS). Findings: From Nov 2020 to May 2021, a total of 11 pts were enrolled, 4 pts havecompleted surgery and 6 pts could be evaluated for ORR. The pCR rate was50%, ORR was 100% (5 PR, 1CR). Adverse events (AEs) of any garde werediarrhea 11 (100.0%), anorexia and vomiting 8 (72.7%) and rash 4 (36.4%).Garde 3 AEs were diarrhea 3 (27.3%), and there was no grade 4 AEs. Conclusion: Pyrotinib combined with trastuzumab and nab-paclitaxel in neoadjuvanttreatment for pts with stage II-III HER2-positive breast cancer showedacceptable toxicity and promising efficacy. Citation Format: Bin Shao, Zhengyan Yu, Yu Wang, Guangcai Zhao, Fei Zhou, Ranmei Wei. A prospective, open, multi-center clinical study of pyrotinib combined with trastuzumab and nab-paclitaxel in neoadjuvant treatment for stage II-III HER2-positive breast cancer patients [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 P2-13-37.

Abstract P5-16-13: Safety and efficacy of INT230-6, a potential first-in-class intratumoral therapy, in monotherapy and in combination with pembrolizumab: Results from the IT-01 study [KEYNOTE-A10] in subjects with locally advanced, unresectable and metastatic breast cancer

Abstract Background: INT230-6 is a novel formulation of cisplatin and vinblastine with an amphiphilic cell penetration enhancer that has been shown to enhance dispersion of the drug throughout tumors and allow diffusion into cells when given intratumorally. INT230-6 is being evaluated in monotherapy and in combination with immune checkpoint inhibitors (ICIs) in subjects with various advanced solid tumors, including advanced breast cancer. Methods: This phase 1/2 study evaluated INT230-6 in superficial and deep tumors with INT230-6 Q2W intratumoral injections for 5 doses alone or in combination with 200mg pembrolizumab IV Q3W for 2 years. Total INT230-6 injected in a subject ranged from 0.89 to 649 mL over 5 INT230-6 dosing sessions in each subject, except one subject who had only 2 dosing sessions. Subjects who had completed treatment in dose escalation cohorts were eligible for retreatment; and one subject was retreated with INT230-6 in multiple arms of the study. Advanced breast cancer subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or below who have failed one or more approved therapies, or have no alternate approved therapy, were enrolled. Subjects must have adequate organ function and measurable disease by RECIST 1.1 criteria including one target tumor for injection. Tumor response using RECIST 1.1 was evaluated at 12 weeks from the first INT230-6 dose and then every 8 weeks. Tumor biopsies were taken prior to INT230-6 dosing on day 0 and on day 28 post dose. Results: 7 advanced triple negative breast cancer subjects (4 monotherapy, 3 pembrolizumab combination) were evaluable as of June 1, 2021. The median age was 56 (range 46-82) years old, with a median of 8 (2, 17) prior systemic therapies for metastatic disease. The intratumoral INT230-6 dose was up to 164 mL (82 mg of CIS, 16.4mg VIN) to tumors in a single dosing session. With INT230-6, 133-200% more volume is injected into the tumor and pharmacokinetics (PK) analysis shows that 95% of INT230-6 active agents remain in the tumor. Accordingly, assessment of tumor response using RECIST principles may be challenging, and even stable disease may represent a large decrease in viable tumor cells as indicated by biopsy evaluations. The most common (&amp;gt;20%) related treatment related adverse events (AE) were localized tumor related pain (71%), nausea (57%), anemia (29%), fatigue (29%), neck pain (29%), and vomiting (29%). AEs were mostly low grade and only one subject experienced grade 3 anemia (13%). There were no related grade 4 or 5 AEs or serious AEs. Disease control rate (DCR), defined as the percent of patients with a complete response, partial response, or stable disease at the first radiologic assessment, was 57%. Median overall survival was 12 months. Pre- and post- biopsy at 28 days after two INT230-6 doses (n= 3 evaluable, monotherapy, and combination with pembrolizumab) showed a 55% decrease in Ki67 and 69% reduction in viable cancer cells. In addition, multiplex immunofluorescence (n= 3 evaluable, combination with pembrolizumab) showed an influx of activated CD4 and CD8 T cells and in some cases a reduction in FoxP3 T-reg cells.. Conclusion: INT230-6 is a potential first-in-class intratumoral therapy for advanced breast cancer being developed in monotherapy and in combination with ICIs. There is a favorable safety profile in this population, similar to the broader metastatic solid tumor population presented elsewhere. There are early signs of cancer cell death in injected tumors and immune activation in heavily pre-treated patients. A Phase 2 expansion cohort of INT230-6 in combination with ICIs is ongoing. In addition, INT230-6 in being studied in a separate randomized Phase 2 neoadjuvant breast cancer study. Citation Format: Philippe Bedard, Lillian L Siu, Jacob Thomas, Diana Hanna, Anthony J Olszanski, Nilofer Azad, Giles Whalen, Matthew Ingham, Syed Mahmood, Lewis H Bender, Ian B Walters, Anthony El-Khoueiry. Safety and efficacy of INT230-6, a potential first-in-class intratumoral therapy, in monotherapy and in combination with pembrolizumab: Results from the IT-01 study [KEYNOTE-A10] in subjects with locally advanced, unresectable and 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 P5-16-13.

Adopting the "Exercise as a Vital Sign" metric to assess physical activity in GI oncology patients.

650 Background: Regular moderate to vigorous physical activity (MVPA) in patients with gastrointestinal (GI) cancers is associated with improved health outcomes, including greater quality of life and reduced fatigue and comorbidity. PA guidelines for cancer survivors recommend ≥150 minutes of MVPA per week for optimal health. Identifying GI oncology patients with low MVPA is important to tailor interventions aimed at increasing MVPA levels in this population. The “Exercise as a Vital Sign” (EVS) tool is a validated, two question assessment tool to quantify minutes per week (min/wk) of MVPA that was incorporated in the clinical rooming process at an academic GI oncology clinic. Here, we report characteristics of patients by amount of MVPA by EVS. Methods: Patient information was entered in the electronic medical record at a large, academic oncology clinic. Data from the first clinic visit where min/wk of MVPA EVS was collected were extracted and included demographics (e.g. age, sex, marital status, race), health status (body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, comorbidities), cancer characteristics (primary tumor site, localized/metastatic, current treatment), and reason for the clinic visit. MVPA was divided into two groups based on the recommended guidelines: 0-149 min/wk (“low”) and ≥150 min/wk (“high”). Chi-square and t-tests were used to examine statistically significant differences. Results: Among 265 patients abstracted, EVS data were reported from 156 (59%) patients. Mean (standard deviation (SD)) age was 61 (13) years (range: 25-82). The primary cancer site was 35% colorectal, 23% pancreatic, 17% gastroesophageal, 10% neuroendocrine, and 15% other GI cancers. While gastroesophageal cancer patients reported high amounts of MVPA (mean (SD) = 268 (309) min/wk), comparisons with other cancer sites were not statistically different. Of the 156 with EVS data, 84 (54%) had low MVPA (mean (SD): 55 (49) min/wk) and 72 (46%) had high MVPA (mean (SD): 357 (244) min/wk). Demographic and cancer characteristics were similar across the two groups. Patients with high MVPA were more likely to have BMI 18.5-24.9 kg/m2 (56% vs. 31%) and less likely to have BMI ≥25 kg/m2 (40% vs.61%) compared to patients with low MVPA (p = 0.02). Patients with high vs. low MVPA were also more likely to have excellent performance status (ECOG 0; 47% vs. 24%, p &lt; 0.001). Conclusions: In this study, GI oncology patients not meeting PA guidelines for cancer survivors were more likely to be overweight/obese and have worse performance status. The EVS tool was an inexpensive and accessible measure of MVPA that can be used to identify patients with low MVPA for interventions targeted to improve health outcomes. A lack of statistical significance may be due to low power. At the conference, more data will be presented (̃1000 patient visits), including longitudinal data and MVPA by active chemotherapy regimen.

Treatment and overall survival among anti-PD-1-exposed advanced melanoma patients with evidence of disease progression.

Background: Little is known regarding treatment patterns and overall survival (OS) for patients with advanced melanoma who progress after anti-PD-1 exposure. Methods: The Kaplan-Meier method was used to evaluate OS from electronic health records for patients with advanced melanoma who progressed on anti-PD-1 therapy and received subsequent therapy. Descriptive statistics were used to summarize treatment. Results: A total of 304 patients who progressed after anti-PD-1 therapy received subsequent therapy: 50% immunotherapy, 36% BRAF and/orMEK inhibitors, 14% other therapies. Median OS was 7.2 months (95% CI: 6.4-8.8), with an association (p<0.01) with best response to baseline anti-PD-1 therapy and further associations with Eastern Co-operative Oncology Group (ECOG)performance status ≤1 (p<0.001 compared with ECOG ≥2), normal LDH(p<0.001 compared with elevated levels) and treatment with BRAF and/or MEK inhibitors (p=0.02 compared with other treatment). There was an association (p<0.01) of survival with best response to baseline anti-PD-1 therapy. Conclusions: OS for advanced melanoma patients who progress on anti-PD-1 therapy is suboptimal, which highlights the need for further research to develop new medications and optimize treatment strategies.