Median Follow-up For Overall Survival Research Articles

Abstract PO5-19-10: First oncological outcomes of HypoG-01: a UNICANCER phase III trial comparing loco-regional hypo vs normo fractionated radiation therapy in early breast cancer patients

Abstract Objective Normofractionated (NF) radiation therapy (RT) is still standard for loco-regional early breast cancer (EBC) in many countries. HypoG-01, a UNICANCER, non-inferiority, open-label, multicenter, randomized phase III trial (NCT03127995), conducted in parallel with the DBCG Skagen trial 1 (NCT02384733), evaluated hypofractionated (HF) RT with 40 Gy/15 fr (2.67 Gy/fr) versus NF RT 50 Gy/25 fr (2.0 Gy/fr). This is the first report of oncological outcomes, secondary endpoints of the trial. Methods Patients (pts) ≥18 years old were operated for T1-3, N0-3, M0 breast cancer. All pts received nodal and thoracic wall or breast RT. Tumor-bed boost (sequential or simultaneous) and nodal levels treated were decided according to local guidelines. Target volumes were delineated according to the ESTRO consensus. RT technique was left at the investigator’s discretion. Stratification factors included treating center, type of surgery, number of positive nodes and body mass index. The primary endpoint, reported previously, was time to occurrence of arm lymphedema. Oncological outcomes included locoregional relapse free survival (LRFS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS), breast cancer specific survival (BCSS) and overall survival (OS) as defined per DATECAN guidelines. All time to cancer related endpoints were defined as starting from the date of randomization until the event. The primary statistic test was stratified one-sided logrank test: 5% significance level in per-protocol population (PPP) with a pre-specified non-inferiority margin of 1.545. Stratified Cox model was used for calculating hazard ratios of oncological outcomes. Results In total, 1265 pts were randomized to HF versus NF RT from Sep 2016 to Mar 2020 with 1221 in the PPP (HF group 614 pts (50.3%); NF group 607 (49.7%)), 5 consent withdrawn and 39 major deviations. Median age was 58 years (range 23-91), surgery included mastectomy (501 pts; 45%) and axillary clearance (921 pts; 82.8%). Sequential (67.8%) or simultaneous integrated (32.2%) tumor-bed boost was used in 596 pts (48.8%). With a median follow-up for OS in PP analysis of 3.8 years (95% CI 3.3 to 3.9), HF was non-inferior to NF RT in terms of lymphedema (HR=1.07; 90% CI 0.86-1.34, non-inferiority p=0.003). Table 1 reports the hazard ratio and 3-year survival rates for the oncological endpoints LRFS, IDFS, DDFS, BCCS and OS. There was no sign of disadvantage for any of these endpoints comparing HF to NF. Additional analyses will be presented at the meeting. Conclusion Moderately HF loco-regional RT is non-inferior to NF RT in terms of lymphedema risk in EBC and does not show a disadvantage in terms of LRFS, IDFS, DDFS, BCCS and OS with a median follow-up of 3.8 years. Together with the Skagen 1 trial, this study provides level 1A evidence supporting the use of 40 Gy/15 fr for loco-regional radiation therapy in EBC with respect to arm lymphedema risk; Table 1: Oncological outcomes according to treatment arm in the per protocol analysis HF: Moderately hypofractionated radiation therapy; NF: Normofractionated radiation therapy; n:number of patients; N: number of events Citation Format: Sofia Rivera, Eleni Karamouza, Youlia Kirova, Séverine Racadot, Mohamed Benchalal, Jean-Baptiste Clavier, Claire Charra-Brunaud, Marie-Eve Chand-Fouche, Delphine Argo-Leignel, Karine Peignaux, Ahmed Benyoucef, David Pasquier, Philippe Guilbert, Julien Blanchecotte, Agnès Tallet, Adeline Petit, Guillemette Bernadou, Xavier Zasadny, Claire Lemanski, Jacques Fourquet, Emmanuelle Malaurie, Honorine Kouto, Carole Massabeau, Alexandre Henni, Pauline Regnault, Aurélie Belliere, Yazid Belkacemi, Magali Le Blanc-Onfroy, Julien Geffrelot, Jean-Briac Prevost, Marie Bergeaud, Assia Lamrani-Ghaouti, Amandine Ruffier, Naima Bonnet, Stephanie Wong, Christine Rossier, Thomas Brion, Pierre Maroun, Claire Petit, Guillaume Auzac, Stefan Michiels. First oncological outcomes of HypoG-01: a UNICANCER phase III trial comparing loco-regional hypo vs normo fractionated radiation therapy in early breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-10.

Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens.

Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens. Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively. Patients with mRCC who received either dual ICI therapy or ICI with VEGF-TKI in the first-line setting were included and were categorized as current, former, or nonsmokers. The primary outcomes were OS, time to treatment failure (TTF), and objective response rate (ORR). OS and TTF were compared between groups using the log-rank test and multivariable Cox regression models. ORR was assessed between the 3 groups using a multivariable logistic regression model. A total of 989 eligible patients were included in the analysis, with 438 (44.3%) nonsmokers, 415 (42%) former, and 136 (13.7%) current smokers. Former smokers were older and included more males, while other baseline characteristics were comparable between groups. Median follow-up for OS was 21.2 months. In the univariate analysis, a significant difference between groups was observed for OS (P = .027) but not for TTF (P = .9), with current smokers having the worse 2-year OS rate (62.8% vs 70.8% and 73.1% in never and former smokers, respectively). After adjusting for potential confounders, no significant differences in OS or TTF were observed among the 3 groups. However, former smokers demonstrated a higher ORR compared to never smokers (OR 1.45, P = .02). Smoking status does not appear to independently influence the clinical outcomes to first-line ICI-based regimens in patients with mRCC. Nonetheless, patient counseling on tobacco cessation remains a crucial aspect of managing patients with mRCC, as it significantly reduces all-cause mortality.

The effect of the relative dose intensity of chemoradiotherapy on the effectiveness of therapy of locally advanced unresectable non-small cell lung cancer

The purpose of the study. To estimate the number of patients with the preservation of relative dose intensity (RDI) ≥ 80 % of first-line antitumor therapy in patients with unresectable non-small cell lung cancer (NSCLC), and to compare the effectiveness of therapy in groups with optimal and lower RDI.Patients and methods. The study included 30 patients (25 men and 5 women) with locally advanced unresectable NSCLC. The median age was 57 years. The main criterion for inclusion in the study was morphologically verified NSCLC with stage IIIB-IIIC of the disease. All patients underwent simultaneous chemoradiotherapy. According to the histogenesis of the tumor process, patients with a squamous cell variant prevailed.Results. The data obtained from 22 (73.3 %) patients who retained a relative dose intensity of RDI > 80 % demonstrated that given dose intensity is sufficient to achieve a stable antitumor effect. In 8 (26.7 %) cases, however, the RDI was less than 80 %, which affected the effectiveness of the treatment. The median follow-up for overall survival (OS) was 29.2 months, progression-free survival (PFS) was 15.1 months, and local control was 21.9 months. in all patients included in the analysis. The indicators of OS in the second year had an advantage in the group of patients with RDI < 80 % and amounted to 73.3 % compared with 60.5 % in patients with RDI > 80 %. PFS was higher in the group of patients with high dose intensity, in the first year of follow-up it was 75.6 % compared with the group of patients with RDI < 80 % (62.5 %), in the second year of follow-up, PFS was 27.2 % and 20.8 %, respectively. Local control was 90.2 % in the first year in the group of patients with RDI > 80 % and 62.5 % in the group of patients with RDI < 80 %. The second year of follow-up demonstrated the advantage of the group of patients with RDI >80 % in terms of local control and amounted to 48.1 % versus 34.7 %, respectively.Conclusion. The results obtained show that maintaining relative dose intensity at a high level has a positive effect on survival rates and local control of patients with locally advanced unresectable NSCLC. However, there is a cohort of patients who did not receive the planned amount of treatment, due to the high toxicity of simultaneous chemoradiotherapy. It is necessary to develop new approaches to concomitant therapy aimed at reducing the toxicity of the combined treatment and achieving maximum antitumor effect.

Testosterone nadir and clinical outcomes in patients with advanced prostate cancer: Post hoc analysis of triptorelin pamoate Phase III studies.

The objective of the study is to evaluate whether low nadir testosterone during treatment with triptorelin pamoate, a luteinising hormone-releasing hormone (LHRH) agonist, is associated with improved clinical outcomes in patients with advanced prostate cancer using a retrospective analysis of clinical trial data. Data were pooled from three prospective, 9-12-month Phase III studies of triptorelin monotherapy in patients with advanced prostate cancer (including NCT00751790). The serum testosterone concentration suppression targets evaluated were <0.35 nmol/L (<10 ng/dl), <0.7 nmol/L (<20 ng/dl), <1.7 nmol/L (<50 ng/dl) and ≥1.7 nmol/L. Overall survival (OS) and disease-specific survival (DSS) by testosterone suppression group were assessed by Kaplan-Meier analysis, with log-rank test. The time frame for the primary analysis was Days 1-518 (median OS follow-up 254 days [range, 29-518 days]) and for the sensitivity analyses was Days 1-262. Supplementary analyses combined the ≥0.7- to <1.7-nmol/L and ≥1.7-nmol/L groups. The sample size comprised 592 patients (most received triptorelin monotherapy; four reported concomitant androgen receptor-axis-targeted therapy). Nadir testosterones of <0.35, ≥0.35 to <0.7, ≥0.7 to <1.7 and ≥1.7 nmol/L were achieved by 96%, 3.2%, 0.34% and 0.17% of patients, respectively. Better OS with decreasing level of nadir testosterone was observed (p < 0.001) and this persisted after sensitivity/supplemental analyses (all p < 0.001). Differences in DSS with decreasing levels of nadir testosterone were not statistically significant in the primary analysis. Sensitivity/supplemental analysis showed better DSS with decreasing level of nadir testosterone (Days 1-262, p = 0.01; combined groups Days 1-518, p = 0.03; combined groups Days 1-262, p = 0.005). Low nadir testosterone achieved during treatment with the LHRH agonist triptorelin was associated with improved OS and DSS in patients with advanced prostate cancer.

Outcome of Newly Diagnosed Children and Adolescents with Localized Lymphoblastic Lymphoma Treated on JPLSG-LLB-NHL03 Trial: A Report from the Japan Children's Cancer Group

Background: Localized lymphoblastic lymphoma (LL) is rare in pediatric patients and have a favorable outcome. Although the Berlin-Frankfurt-Münster (BFM) 90/95 protocol has been considered standard therapy, this regimen is too intense for patients with localized disease and the total doses of anthracycline and alkylating agents are high. To resolve these problems, we planned a clinical trial to examine the efficacy and safety of a modified BFM regimen for patients with localized LL. We report the 3-year event-free survival (EFS) and overall survival (OS) rate for children and adolescents with localized LL treated on JPLSG-LLB-NHL03 trial. Procedure: From November 2004 to October 2019, 41 newly diagnosed patients up to 18 years of age enrolled on LLB-NHL03 with localized LL (Murphy stages I and II) and with either T- or B- cell immunophenotype. Staging procedures included: bilateral bone marrow aspirates and biopsies, lumbar puncture, CT or MRI of abdomen, chest X-ray, and bone scintigraphy or whole body bone X-ray. Central pathology review consisted of examination of morphology and immunophenotypic and any available genetic data from the original diagnostic biopsy to confirm the submission diagnosis and assign phenotypic lineage. Treatment consisted of 5 phases: induction (prednisolone 60mg/m 2, day 0-27; vincristine 1.5mg/m 2, day0,7,14,21; cyclophosphamide 1g/m 2, day 0; daunorubicin 30mg/m 2, day 0,7; E.coli L-asparaginase 6,000 units/m 2, 9 total doses, and intrathecal methotrexate and hydrocortisone, day 0,14), consolidation (mercaptopurine 60mg/m 2, day 0-27; cyclophosphamide 500mg/m 2, day0,14; cytarabine 75mg/m 2, 12 total doses and intrathecal therapy methotrexate and hydrocortisone, day 0,14) , CNS prophylaxis (high dose methotrexate 3g/m 2, day0,7,14; and intrathecal methotrexate and hydrocortison, day 0. Standard leucovorin dosing, 15mg/m 2 intravenous every 6h, is delivered 36h after the start of the methotrexate infusion and is continued until methotrexate levels are less than 0.1 μmol/L.), delayed intensification (prednisolone 60mg/m2, day 0-13; vincristine 1.5mg/m 2, day 0,7,14; cyclophosphamide 1g/m 2, day0; daunorubicin 30mg/m 2, day 0,7; L-asparaginase 6,000 units/m 2, 6 total doses and intrathecal methotrexate and hydrocortison, day 0,14), and maintenance (mercaptopurine 60mg/m 2 daily and methotrexate 20mg/m 2 weekly). Total duration of therapy was 24 months from diagnosis. Patients received 120mg/m 2 of anthracycline (daunorubicin) , 3 g/m 2 of cyclophosphamide and 7 doses of intrathecal therapy. Results: Of the 41 patients enrolled in the study, 35 were included in the primary efficacy and safety analysis, excluding 6 patients because they did not meet the eligibility criteria: three with diffuse large B-cell lymphoma, one with extranodal NK/T lymphoma, one with mixed phenotype LL, and one with stage III disease. Themedian [range] age at enrollment was 9.0 [2.1-16.1] years. Twenty-three (65.7%) were male. Twenty-nine had pre-B and 6 had pre-T immunophenotype. Fifteen (42.9%) were Stage I and 20 (57.1%) were Stage II. Thirty-four (97%) patients achieved complete remission at the end of induction. The median follow-up for EFS was 10.1 [0.0-15.2] years, and the primary endpoint of 3-year EFS rate [95% confidence interval: 95% CI] (n=35) was 97.1% [81.4-99.6%]. (Fig.1) The median follow-up for OS was 10.6 [2.9-16.1] years, and the 3-year OS rate (n=35) was 100%. One pre-T immunophenotype patient with stage II disease failed to achieve complete remission after induction therapy. Overall, patients tolerated therapy well and no treatment-related deaths were observed. There was only one unanticipated adverse event (retinal detachment), and a causal relationship to study treatment was ruled out. Conclusion: This is the largest trial ever conducted in the treatment of pediatric patients with newly diagnosed localized lymphoblastic lymphoma using an individual protocol. Outcomes of pediatric patients with localized LL treated with 2 years of less-intensive BFM-like therapy was excellent. The number of children diagnosed with localized LL limits the possibility of randomized trials focusing on therapeutic questions. Future studies should identify the biologic or clinical difference between LL and lymphoblastic leukemia, explore less intensive treatment for patients with localized disease, and explore novel targeted therapies.

Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial

PROpel met its primary endpoint showing statistically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in patients with first-line metastatic castration-resistant prostate cancer (mCRPC) unselected by homologous recombination repair mutation (HRRm) status, with benefit observed in all prespecified subgroups. Here we report the final prespecified overall survival analysis. This was a randomised, double-blind, phase 3 trial done at 126 centres in 17 countries worldwide. Patients with mCRPC aged at least 18 years, Eastern Cooperative Oncology Group performance status 0-1, a life expectancy of at least 6 months, with no previous systemic treatment for mCRPC and unselected by HRRm status were randomly assigned (1:1) centrally by means of an interactive voice response system-interactive web response system to abiraterone acetate (orally, 1000 mg once daily) plus prednisone or prednisolone with either olaparib (orally, 300 mg twice daily) or placebo. The patients, the investigator, and study centre staff were masked to drug allocation. Stratification factors were site of metastases and previous docetaxel at metastatic hormone-sensitive cancer stage. Radiographic progression-free survival was the primary endpoint and overall survival was a key secondary endpoint with alpha-control (alpha-threshold at prespecified final analysis: 0·0377 [two-sided]), evaluated in the intention-to-treat population. Safety was evaluated in all patients who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03732820, and is completed and no longer recruiting. Between Oct 31, 2018 and March 11, 2020, 1103 patients were screened, of whom 399 were randomly assigned to olaparib plus abiraterone and 397 to placebo plus abiraterone. Median follow-up for overall survival in patients with censored data was 36·6 months (IQR 34·1-40·3) for olaparib plus abiraterone and 36·5 months (33·8-40·3) for placebo plus abiraterone. Median overall survival was 42·1 months (95% CI 38·4-not reached) with olaparib plus abiraterone and 34·7 months (31·0-39·3) with placebo plus abiraterone (hazard ratio 0·81, 95% CI 0·67-1·00; p=0·054). The most common grade 3-4 adverse event was anaemia reported in 64 (16%) of 398 patients in the olaparib plus abiraterone and 13 (3%) of 396 patients in the placebo plus abiraterone group. Serious adverse events were reported in 161 (40%) in the olaparib plus abiraterone group and 126 (32%) in the placebo plus abiraterone group. One death in the placebo plus abiraterone group, from interstitial lung disease, was considered treatment related. Overall survival was not significantly different between treatment groups at this final prespecified analysis. Supported by AstraZeneca and Merck Sharp & Dohme.

Tumor-Free Resection Margin Distance in the Surgical Treatment of Node-Negative Squamous Cell Cancer of the Vulva Has No Impact on Survival: Analysis of a Large Patient Cohort in a Tertiary Care Center.

The aim of this study was to evaluate the impact of pathological tumor-free margin distance on survival in SCC patients treated with surgery alone. This retrospective study included 128 patients with node-negative disease that received no adjuvant treatment. Disease-free and overall survival were analyzed according to pathological tumor-free margin distance. The patients were subclassified into three resection margin category groups: "1 to 3 mm" (n = 42), ">3 to 8 mm" (n = 47) or ">8 mm" (n = 39). Thirty-nine of the 128 patients (30.5%) developed recurrent disease. Median follow-up for disease-free survival (DFS) was 6.49 years (95% CI 5.16 years; 7.62 years), and median follow-up for overall survival (OS) was 6.29 years (95% CI 5.45 years; 7.33 years). The 5-year DFS rate was 0.70 (95% CI: 0.62-0.79), and the 5-year OS rate was 0.79 (95% CI: 0.71-0.87). Regarding the survival outcome, there were no independent significant differences in either disease-free survival (DFS) (p = 0.300) or overall survival (p = 1.000) among patients within the three tumor-free resection margin categories. Multivariate analyses did not show any statistically significant association between tumor-free resection margin distance and recurrent disease or death, either when analyzed as a categorical variable or when analyzed as a continuous variable. The present study did not show a significant impact of pathological tumor-free resection margin distance following surgery in patients with node-negative SCC of the vulva (that did not receive adjuvant treatment) on disease-free and overall survival.

Overall survival analysis from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC).

LBA3 Background: Osimertinib is a third-generation, central nervous system (CNS) active EGFR-TKI, that potently and selectively inhibits EGFR-TKI sensitizing and EGFR T790M resistance mutations. In the primary analysis from the Phase III ADAURA study (NCT02511106), adjuvant osimertinib demonstrated a clinically meaningful, statistically significant, and practice-changing disease-free survival (DFS) benefit vs placebo in patients with completely resected EGFRm (ex19del/L858R) NSCLC ± adjuvant chemotherapy. In an updated DFS analysis, with 2 years additional follow-up, DFS and CNS DFS benefit with adjuvant osimertinib were sustained (stage II–IIIA DFS hazard ratio [HR] 0.23; 95% confidence interval [CI] 0.18, 0.30; stage IB–IIIA DFS HR 0.27; 95% CI 0.21, 0.34; stage II–IIIA CNS DFS HR 0.24; 95% CI 0.14, 0.42), with a tolerable safety profile observed over the extended treatment duration. Here, we report the planned final overall survival (OS) analysis from ADAURA. Methods: Eligible patients (aged ≥18 years [≥20 in Japan and Taiwan], WHO PS 0/1 with completely resected EGFRm (ex19del/L858R) stage IB, II or IIIA [AJCC/UICC 7th edition] NSCLC; adjuvant chemotherapy allowed) were randomized 1:1 to osimertinib 80 mg once daily or placebo until disease recurrence, treatment completion (3 years), or a discontinuation criterion was met. The primary endpoint was investigator-assessed DFS in stage II–IIIA. Key secondary endpoints: DFS in stage IB–IIIA, OS and safety. Data cut-off: January 27, 2023. Results: Globally, 682 patients were randomized; osimertinib n=339, placebo n=343. Adjuvant osimertinib significantly improved OS vs placebo. In patients with stage II–IIIA disease, OS HR was 0.49 (95% CI 0.33, 0.73; p=0.0004; 100/470 events, 21% maturity); 5-year OS rate was 85% with osimertinib vs 73% with placebo. Median follow-up for OS in stage II–IIIA was 59.9 months (osimertinib) and 56.2 months (placebo). In the overall population (stage IB–IIIA), OS HR was 0.49 (95% CI 0.34, 0.70; p&lt;0.0001; 124/682 events, 18% maturity); 5-year OS rate was 88% with osimertinib vs 78% with placebo, with a median follow-up for OS of 60.4 months (osimertinib) and 59.4 months (placebo). Median OS was not reached in either population or treatment group. Conclusions: Adjuvant osimertinib demonstrated an unprecedented, highly statistically significant and clinically meaningful OS benefit in patients with EGFRm stage IB–IIIA NSCLC after complete tumor resection, with or without adjuvant chemotherapy. ADAURA is the first global Phase III study to demonstrate a statistically significant DFS and OS benefit with targeted treatment for patients with EGFRm stage IB–IIIA NSCLC. Clinical trial information: NCT02511106 .

An exploratory clinical trial on intra-lumbar injection of B7H3-specific allogeneic universal CAR-T cells in patients with recurrent high-grade gliomas.

2043 Background: No standard-of-care treatment was established for recurrent high-grade gliomas (rHGGs) yet. Intrathecal infusion of autologous chimeric antigen receptor-T (CAR-T) cells has displayed potent anti-tumor activity in one patient (Brown et al. N Engl J Med 2016). We evaluated the safety, efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of B7H3-specific allogeneic universal CAR-T (B7H3 UCAR-T) cells in patients with rHGGs. Methods: Eligible patients who had received standard treatment for newly-diagnosed high-grade gliomas but failed were treated with 2.5×107 B7H3 UCAR-T cells via intra-lumbar injection every month. Eligibility criteria included histologic and/or cytologic rHGGs, B7H3-positive antigen expression rate of &gt;50% in tumor tissue and Karnofsky performance status (KPS) ≥ 40. The primary endpoint was treatment-related adverse events (TAEs); secondary endpoints include overall survival (OS) and objective response rate (ORR); exploratory endpoints were PK and PD characteristics of B7H3 UCAR-T cells. Results: In the 7 patients enrolled, 4 (57.1%) were female, 5 (71.4%) glioblastoma (WHO Grade IV) and 2 (28.6%) diffuse midline glioma (WHO Grade IV), and the mean age was 40.4 years. The most common reported TAEs were increased cerebrospinal fluid (CSF) IL-6 (7/7, 100%), headache (7/7, 100%), increased blood IL-6 (6/7, 86%) and fever (6/7, 86%). No adverse events of grade 3 or greater related to B7H3 UCAR-T cells were reported. All the adverse events recovered or relieved after treatment. No typical or severe systemic cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) or graft versus host disease (GvHD) were observed during the study period. Based on Immunotherapy Response Assessment in Neuro-Oncology (iRANO), 3 of 7 patients had response to therapy (42.9%; 95% CI: 15.8 to 75.0) and 7 of 7 patients were stable disease (100%; 95% CI: 64.6 to 100). As of cutoff date (January 30, 2023), two patients died. The median OS was not reached (95% CI: 12.9 to could not be estimated). The median follow-up for OS was 15.6 months (95% CI: 14.7 to 16.1). OS rate at 12 months was 85.7% (95% CI: 48.7 to 97.4). The CAR DNA copy numbers increased 1 day after each administration and persist at least 1 month in cerebrospinal fluid. IL-6 concentrations in CSF and peripheral blood increased after each administration while the change and concentration values in peripheral blood were much lower than those in CSF. Conclusions: In patients with rHGGs, B7H3 UCAR-T cells was not associated with any toxic effects of grade 3 or higher. B7H3 UCAR-T cells resulted in a significantly longer overall survival and a higher objective response rate than history data. B7H3 UCAR-T cells persist well in patients. Clinical trial information: ChiCTR2100047968 .

Abstract CT153: Pemigatinib in Chinese patients with advanced/metastatic or surgically unresectable cholangiocarcinoma Including FGFR2 fusion or rearrangement: Updated overall survival from an open-label, single-arm, multicenter Phase II study

Abstract Background: Pemigatinib is a selective FGFR inhibitor that showed effectiveness and tolerability in patients with cholangiocarcinoma (CAA) with FGFR2 fusion or rearrangement. Data from prior data cutoffs (primary: Jan 29th, 2021; initial update: Dec 20th, 2021) showed that patients receiving pemigatinib had durable responses. Confirmed objective response rate (ORR) (60%) met the primary endpoint, median duration of response (DOR) was 8.3 months, median progression-free survival (PFS) was 9.1 months at the initial update (G-M. Shi et al. ASCO 2022). Safety results were also consistent with previously reported data on pemigatinib. Here we report updated overall survival (OS) results. Methods: Patients aged 18 years or older with recurrent or metastatic CCA that failed at least one prior systemic therapy were enrolled. Thirty-one subjects with documented FGFR2 fusion or rearrangement received 13.5 mg pemigatinib. The primary efficacy endpoint was ORR assessed by the independent radiological review committee (IRRC) per RECIST V1.1. And the second endpoints included disease control rate (DCR), DOR, PFS, and OS. Updated OS were evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods. Results: At data cutoff (December 28th, 2022), a total of 30 patients were assessed (1 participant excluded due to inadequate FGFR2 aberrant frequency). Median age was 56 years (range, 28-68).With a median OS follow-up of 25.6 months (95% CI, 23.0-25.8), the median OS was 23.9 months (95% CI, 15.2-NC), with 16 (53.3%) OS events. Estimated OS rate at 12 month, 18 month and 24 month were 73.3% (95% CI, 53.7%-85.7%), 66.5% (95% CI, 46.7%-80.4%), and 41.4% (95% CI, 22.4%-59.4%), respectively. No new safety signals were observed. Conclusions: These updated results demonstrated encouraging and durable survival benefit of pemigatinib in Chinese patients with recurrent or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangement. Clinical trial identification: NCT04256980. Editorial acknowledgment: Guoming Shi and Xiaoyong Huang contributed equally to this work. Jian Zhou is the corresponding author. Citation Format: Guoming Shi, Xiaoyong Huang, Tianfu Wen, Tianqiang Song, Ming Kuang, Haibo Mou, Lequn Bao, Haitao Zhao, Hong Zhao, Xielin Feng, Bixiang Zhang, Tao Peng, Yubao Zhang, Xiangcheng Li, Hongsheng Yu, Yu Cao, Yang Luo, Ye Chen, Mingxia Chen, Jia Fan, Jian Zhou. Pemigatinib in Chinese patients with advanced/metastatic or surgically unresectable cholangiocarcinoma Including FGFR2 fusion or rearrangement: Updated overall survival from an open-label, single-arm, multicenter Phase II study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT153.

Blood- and Imaging-Derived Biomarkers for Oncological Outcome Modelling in Oropharyngeal Cancer: Exploring the Low-Hanging Fruit

To assess whether CT-based radiomics and blood-derived biomarkers could improve the prediction of overall survival (OS) and locoregional progression-free survival (LRPFS) in patients with oropharyngeal cancer (OPC) treated with curative-intent RT. Consecutive OPC patients with primary tumors treated between 2005 and 2021 were included. Analyzed clinical variables included gender, age, smoking history, staging, subsite, HPV status, and blood parameters (baseline hemoglobin levels, neutrophils, monocytes, and platelets, and derived measurements). Radiomic features were extracted from the gross tumor volumes (GTVs) of the primary tumor using pyradiomics. Outcomes of interest were LRPFS and OS. Following feature selection, a radiomic score (RS) was calculated for each patient. Significant variables, along with age and gender, were included in multivariable analysis, and models were retained if statistically significant. The models' performance was compared by the C-index. One hundred and five patients, predominately male (71%), were included in the analysis. The median age was 59 (IQR: 52-66) years, and stage IVA was the most represented (70%). HPV status was positive in 63 patients, negative in 7, and missing in 35 patients. The median OS follow-up was 6.3 (IQR: 5.5-7.9) years. A statistically significant association between low Hb levels and poorer LRPFS in the HPV-positive subgroup (p = 0.038) was identified. The calculation of the RS successfully stratified patients according to both OS (log-rank p < 0.0001) and LRPFS (log-rank p = 0.0002). The C-index of the clinical and radiomic model resulted in 0.82 [CI: 0.80-0.84] for OS and 0.77 [CI: 0.75-0.79] for LRPFS. Our results show that radiomics could provide clinically significant informative content in this scenario. The best performances were obtained by combining clinical and quantitative imaging variables, thus suggesting the potential of integrative modeling for outcome predictions in this setting of patients.

32O 5-year (y) overall survival (OS) with maintenance olaparib (ola) plus bevacizumab (bev) by clinical risk in patients (pts) with newly diagnosed advanced ovarian cancer (AOC) in the phase III PAOLA-1/ENGOT-ov25 trial

In the PAOLA-1/ENGOT-ov25 trial, adding maintenance ola to bev improved progression-free survival in homologous recombination deficiency-positive (HRD+; tumour BRCA1/2 mutation [tBRCAm] and/or genomic instability) pts with newly diagnosed AOC at higher and lower risk of progression by disease stage and surgical status. Greatest benefits were seen in lower-risk pts (Harter et al. Gynecol Oncol 2022). Here, we analysed 5-y OS according to clinical risk and HRD status. Pts in response after first-line platinum-based chemotherapy + bev were randomized 2:1 to ola (300 mg bid; up to 24 months [mo]) + bev (15 mg/kg q3w; up to 15 mo) or placebo [pbo] + bev. This post hoc exploratory analysis evaluated OS in pts classified as higher risk (stage III with upfront surgery and residual disease or neoadjuvant chemotherapy; stage IV) or lower risk (stage III with upfront surgery and no residual disease), and by HRD status. 537 pts were randomized to ola + bev and 269 to pbo + bev (median OS follow-up 61.7 and 61.9 mo, respectively). Of 806 randomized pts, 595 (74%) were classified as higher risk and 211 (26%) as lower risk. At final data cutoff (22 March 2022), OS events had occurred in 377 higher-risk pts (data maturity 63%) and 69 lower-risk pts (data maturity 33%). OS was prolonged with ola + bev in higher- and lower-risk pts with a tBRCAm or who were HRD+. No OS benefit was seen in HRD− pts in any clinical risk subgroup. Subsequent PARP inhibitor therapy was received by 19.5% and 19.6% of ola + bev pts, and 45.9% and 45.2% of pbo + bev pts, in higher- and lower-risk groups, respectively.Table: 32OHRD statusHigher risk (n=595)Lower risk (n=211)No. of events/no. of pts (%)5-y OS rate† (%)No. of events/no. of pts (%)5-y OS rate† (%)Ola + bevPbo + bevOla + bevPbo + bevOla + bevPbo + bevOla + bevPbo + bevFull analysis set249/399 (62)128/196 (65)38.535.339/138 (28)30/73 (41)72.758.3HRD+*82/177 (46)53/89 (60)55.242.211/78 (14)16/43 (37)88.361.3tBRCAm43/109 (39)29/55 (53)65.248.35/48 (10)8/25 (32)91.466.1HRD−116/144 (81)46/62 (74)18.226.324/48 (50)12/23 (52)48.048.5HRD status by Myriad MyChoice HRD Plus assay; tBRCAm status by central labs.*HRD+ defined as a tBRCAm and/or genomic instability score of ≥42 on the Myriad MyChoice HRD Plus assay; †Kaplan–Meier estimates. Open table in a new tab HRD status by Myriad MyChoice HRD Plus assay; tBRCAm status by central labs. *HRD+ defined as a tBRCAm and/or genomic instability score of ≥42 on the Myriad MyChoice HRD Plus assay; †Kaplan–Meier estimates. This post hoc analysis of 5-y OS suggests that adding maintenance ola to bev should be considered for all HRD+ pts with newly diagnosed AOC, irrespective of their clinical risk status. Particular benefit was observed in HRD+ lower-risk pts who achieved 5-y OS rates of 88.3%.

Surgical resection versus transarterial chemoembolization followed by moderately hypofractionated radiotherapy in hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is the gold standard treatment in intermediate hepatocellular carcinoma (HCC), but long-term disease control rates remain low. Herein, we compared results of TACE followed by hypofractionated radiotherapy (TACE-hRT) to surgical resection (SR) in early single or paucinodular intrahepatic HCC. Between June 2004 and November 2016, data on 160 consecutive patients with Barcelona Clinic Liver Cancer (BCLC) stageA Child-PughA HCC treated with SR or TACE-hRT in our expert center were retrospectively reviewed. Time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were evaluated. Clinical outcomes were compared using the stabilized-weights inverse probability of treatment weighting propensity score. Ninety-eight patients underwent SR and 62were treated by TACE-hRT. Median total dose of RT was 54 Gy (interquartile range [IQR] 54-54) in 3‑Gy fractions. Median OS follow-up was 93months. TTP did not significantly differ between patients following SR and TACE-hRT, with 1‑year rates of 68.2% and 82.6% (p = 0.17), respectively. In contrast, PFS and OS were lower in the TACE-hRT group (p = 0.015 and p = 0.006), with amedian OS of 37vs. 63months for patients with surgery and TACE-hRT, respectively. In multivariate analysis, asignificant negative impact on PFS and OS was seen for age at diagnosis, on TTP for alcohol-related liver disease, and on OS for total number of HCC nodules. Symptomatic grade ≥ 3 adverse events were presented by42 (42.9%) SR and19 (30.6%) TACE-hRT patients (p = 0.17). In patients presenting Child-PughA BCLC‑A HCC with high risk for surgical complications, TACE-hRT can be an effective and safe treatment. However, surgical management remains the standard of care whenever possible.

CREST-UK: CPX-351 Real-World Effectiveness and Safety Study for the Treatment of Newly Diagnosed Therapy-Related AML and AML with Myelodysplasia-Related Changes in the UK

Background: In the UK, CPX-351 (Vyxeos® liposomal) has been licensed since August 2018 for adults with newly diagnosed, therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC), primarily based on favorable outcomes for CPX-351 versus 7+3 chemotherapy in a phase 3 trial in adults aged 60 to 75 y with newly diagnosed, high-risk/secondary AML. However, the phase 3 trial population did not reflect the full CPX-351 licensed population. As a complement to the phase 3 trial and to address important data gaps, CREST-UK was performed to assess the effectiveness and safety of CPX-351 in routine clinical practice in the UK and observe the impact of COVID-19 infection in these patients (pts). Methods: CREST-UK is a retrospective, noninterventional, multicenter, single-arm, observational study (NCT05169307) that collected pseudonymized pt data abstracted from the medical records of adults aged ≥18 y with newly diagnosed t-AML or AML-MRC (per WHO 2016 criteria) who received ≥1 infusion of CPX-351 in routine practice; pts who received CPX-351 in a clinical trial were excluded. The primary objective was to describe complete remission (CR or CRi) and overall survival (OS). Key secondary objectives described pt and disease characteristics, frequency of hematopoietic cell transplantation (HCT), OS landmarked from the HCT date, and the CPX-351 safety profile. Median follow-up for OS was 10.6 mo (interquartile range [IQR]: 4.5, 18.4). Results: A total of 147 pts who received their first CPX-351 induction from November 2018 to March 2022 were included from 15 centers. Median age was 64 y (range: 18, 83), with 17 (12%) pts aged <45 y, 39 (27%) aged 45-59 y, 64 (44%) aged 60-69 y, and 27 (18%) aged ≥70 y. Overall, 35 (24%) pts had t-AML and 112 (76%) had AML-MRC (n=43 with prior MDS, n=9 with prior CMML, n=41 with MDS-related cytogenetics, and n=19 with multilineage dysplasia alone); 13 (9%) had received prior azacitidine. The majority (90%) of pts had an ECOG performance status ≤1. Disease risk by European LeukemiaNet 2017 criteria was favorable for 13 (9%) pts, intermediate for 39 (27%), adverse for 66 (45%), and unknown for 29 (20%) due to limited mutational data. Complex karyotype, monosomal karyotype, and/or abn(17p) were reported for 37 (25%) pts. TP53 mutations were reported for 15/66 (23%) pts with evaluable data. A best response of CR+CRi was achieved by 73/138 (53%) evaluable pts, and overall response (CR+CRi+MLFS+PR) was achieved by 88/138 (64%) pts. Post induction, 19/37 (51%) pts in CR or CRi with a known measurable residual disease (MRD) status achieved MRD negativity; 3 additional pts achieved MRD negativity at a later time point. Kaplan-Meier median OS was 12.85 mo (95% CI: 9.2, 15.4; Fig 1), with 2- and 3-y OS estimates of 36% and 34%, respectively. Fifty (34%) pts proceeded to HCT; median OS landmarked from the HCT date was not reached (Fig 2), with a 2-y OS estimate of 71%. Among pts in CR or CRi, median recovery (IQR) to neutrophils ≥500/μL was 33 d (28, 43) and to platelets ≥50,000/μL was 34 d (27, 48) during the first induction. Grade ≥3 treatment-related adverse events (TRAEs) of interest included febrile neutropenia (36%; n=1 grade 5), infections (29%; n=6 grade 5), bleeding (4%; n=1 grade 5), and gastrointestinal events (3%). Cardiac TRAEs of any grade were reported for 5% of pts, with grade ≥3 events in 3% (n=1 grade 5). No extravasation was reported. Estimated all-cause mortality was 7% at 30 d and 14% at 60 d. This study included pts who were diagnosed and treated for AML during the COVID-19 pandemic. A total of 26 COVID-19 infections happened at variable time intervals pre- or post-AML treatment. In this cohort, 2 deaths were directly linked to COVID-19; both were assessed by the site investigator as unrelated to CPX-351 treatment. Conclusion: CREST-UK, a real-world study in the context of the COVID-19 pandemic, confirmed the efficacy and safety of CPX-351 in a broad population that included substantial proportions who were aged <60 y or ≥70 y and/or had adverse-risk disease. CR or CRi with MRD negativity and/or proceeding to HCT was achieved in proportions consistent with clinical trials and other real-world studies. Survival outcomes were also consistent with other real-world studies. No new safety concerns with CPX-351 were identified. These data provide new insights into the use of CPX-351 in routine clinical practice in the UK and support its continued use in adults with newly diagnosed t-AML and AML-MRC. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Survival of elderly patients with HER2+/HR- metastatic breast cancer in clinical practice: SEER-Medicare data 2012-2016.

1039 Background: Older patients with human epidermal growth factor 2-positive (HER2+) metastatic breast cancer(mBC) are underrepresented in clinical trials. We aim to assess the overall survival (OS) and breast cancer-specific survival of elderly women with de novo HER2+/hormone receptor-negative (HR-) mBC in a real-world setting. Methods: Elderly women with HER2+/HR- mBC treated with chemotherapy and/or HER2-targeted agents and with continuous Medicare Part A, B, and D coverage 1-year before diagnosis were identified from the SEER-MEDICARE database 2012-2016. Patients were retrospectively followed from metastatic diagnosis until death, disenrollment from Medicare A, B, or D, or end of the observation period. Patients' year and month of diagnosis and death were retrieved from SEER. Death dates were verified with Medicare records reported by the Social Security Administration (SSA). For all-cause deaths, Kaplan-Meier analysis was used to estimate overall survival. The cumulative incidence competing risk (CICR) method based on cumulative incidence function (CIF) was used to estimate breast cancer-specific death incidence. Results: Seventy-three patients (mean age at diagnosis, 75.0±7.7 years) met the inclusion criteria. Among them, 56 were treated with trastuzumab ± pertuzumab /chemotherapy as first-line treatment, and 17 were treated with chemotherapy only. The median time to initiate trastuzumab-based treatment from diagnosis was 2.5 months, and the longest trastuzumab treatment length was over 44 months. The median follow-up for OS was 13 months. One patient developed stomach cancer 6 months after breast cancer diagnosis. In Kaplan-Meier analysis, censoring or not censoring this patient after second cancer development resulted in a median OS of 19 months (95% CI, 9-24 months) and 18 months (95% CI, 9-22 months). The OS at the end of 46 months was approximately 25%. Five patients died from other causes, including lung cancer, cerebrovascular diseases, aortic aneurysm and dissection, pneumonia and influenza, and heart diseases during treatment. Considering these competing risks, 50% (95% CI, 36%-64%) of patients specifically died from breast cancer between 21 and 22 months, estimated by the CICR method. Conclusions: Our study observed a shorter OS among HER2+/HR- mBC elderly patients in clinical practice than the OS of 40.8 and 56.5 months among younger patients in the CLEOPATRA trial, suggesting that age is an important prognostic factor for breast cancer survival. The presence of second cancer and other competing risks led to overestimating the probabilities of breast cancer-specific death and resulted in a shorter OS using the Kaplan-Meier method. The CICR method is more relevant to estimate the breast-cancer-specific death incidence.

Updated efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase (TRK) fusion lung cancer.

9024 Background: Neurotrophic tyrosine receptor kinase ( NTRK) gene fusions have been identified as oncogenic drivers in a variety of tumor types, including lung cancer. Larotrectinib is a highly selective, central nervous system (CNS)-active TRK inhibitor that demonstrated an objective response rate (ORR) of 73% across 15 investigator-assessed patients (pts) with lung cancer (Drilon et al, JCO Precis Oncol 2022). We report data on an expanded cohort of pts with TRK fusion lung cancer treated with larotrectinib. Methods: Pts with TRK fusion lung cancer enrolled in two larotrectinib clinical trials (NCT02576431 and NCT02122913) were included for this analysis. Larotrectinib was administered at 100 mg twice daily. Response was assessed by independent review committee (IRC) per RECIST v1.1. Results: As of July 20, 2021, a total of 26 pts with TRK fusion lung cancer (24 non-small cell lung cancer, 1 atypical carcinoid, 1 neuroendocrine) were enrolled, including 10 pts with CNS metastases at baseline. Median age was 51.5 years (range 25.0–76.0). The gene fusions involved NTRK1 (n =21; 81%) or NTRK3 (n =5; 19%). Pts received a median of 2 prior lines of systemic therapies with 19 (73%) receiving ≥2. Among 23 pts evaluable per IRC, the ORR was 83% (95% confidence interval [CI] 61–95): two complete responses, 17 partial responses (PR), and four stable disease (SD). The median time to response was 1.8 months. Among 10 evaluable pts with baseline CNS metastases, the ORR was 80% (95% CI 44–97): eight PR and two SD. Median duration of response (DoR) and progression-free survival (PFS) were not reached; median follow-up was 12.9 and 14.6 months, respectively. The 24-month rates for DoR and PFS were 72% and 67%, respectively. Median follow-up for overall survival (OS) was 12.9 months. The 24-month and 36-month rates for OS were both 72%. For the 10 evaluable pts with CNS metastases, the 12-month DoR, PFS, and OS rates were 26%, 22%, and 78%, respectively. Duration of treatment for all pts evaluable per IRC ranged from 2.1 to 52.7+ months. At data cut-off, six pts had progressed, with all six continuing treatment post-progression for ≥4 weeks. Treatment-related adverse events (TRAEs) were predominantly Grade 1–2. Grade 3–4 TRAEs were reported in five pts (increased alanine aminotransferase, increased aspartate aminotransferase, hypersensitivity, myalgia, and increased weight). There were no treatment discontinuations due to TRAEs. Conclusions: In this larger dataset, larotrectinib demonstrated rapid and durable responses, extended survival, and a favorable long-term safety profile in pts with advanced lung cancer harboring NTRK gene fusions, including in pts with CNS metastases. These results support testing for NTRK gene fusions in pts with lung cancer. Clinical trial information: NCT02576431, NCT02122913.

LungTS: A new gene expression signature for prediction of response to checkpoint inhibitors in non-small cell lung cancer.

e21143 Background: Immune checkpoint inhibitors (ICIs) are associated with durable antitumor activity in advanced non-small cell lung cancer (NSCLC), however, selection of the best candidates for this type of therapy is a challenge. PD-L1 expression, the only adequately validated predictive biomarker of response to ICIs, is imperfect, and not completely discriminatory between responders and non-responders. Gene expression profile (GEP) is a promising way to evolve in this field. The objective of this study was to identify a GEP of immune-oncology related genes, predictive of response to ICIs in NSCLC. Methods: This study analyzed two cohorts of advanced NSCLC patients treated with ICIs in any line: a discovery cohort composed of 66 Brazilian patients and a validation cohort composed of 54 Spanish patients. Clinical data were collected from medical records. Total RNA was extracted from FFPE tumor tissue. Gene expression profile (GEP) was assessed using the nCounter PanCancer IO360 panel (NanoString Technologies), which comprises 770 genes involved in the cancer immune response. LASSO regression with Cox proportional hazards approach was used to define the new gene expression signature. Results: In the discovery cohort, median age was 62.5 years (36 - 81 years). Most patients were males (57.6%), stage IV (91.9%), ECOG-PS≤1 (90.7%), smokers/former smokers (83.3%) and had adenocarcinoma histology (67.7%). The majority was treated with ICI in the first-line setting (42.4%) and nivolumab was the most frequently used drug (52.6%). At data cutoff, median follow-up for overall survival (OS - time from ICI initiation to death by any cause) was 27.7 months and for real-world progression-free survival (rwPFS - time from ICI initiation to disease progression as assessed by treating physician) was 28.2 months. The median OS and rwPFS were 17.7 months and 5.6 months, respectively. We identified a 6-gene signature (Lung Tumor Score – LungTS) that discriminate patients at low and high risk for death (median OS: 36.1 vs 15.5 months; p &lt; 0.001) and for disease progression (median rwPFS: 10.1 vs 4.2 months; p &lt; 0.001). Considering the expression of CD274 (PD-L1), the LungTS signature also discriminated two populations regarding OS and rwPFS (p &lt; 0.0001). In the validation cohort, which had clinicopathological characteristics similar to the discovery cohort, the OS for high versus low LungTS was 17.0 months and 9.0 months, respectively (p = 0.004). Patients with high score also showed better rwPFS, although not statistically significant (median 10.0 versus 4.0 months; p = 0.11). Conclusions: Our study identified a novel 6-gene immune-signature predictive of response to ICI in NSCLC.

Serum glycoproteomic signatures and association with survival in patients with bone and soft tissue sarcoma treated with immune-checkpoint inhibitor therapy.

11546 Background: Glycosylation is one of the most ubiquitous and functionally important forms of post-translational modification. The role of differential glycosylation in serum proteins has so far been limited by the technical complexity inherent in generating and interpreting this information. InterVenn has built a novel platform that combines liquid chromatography/mass spectrometry with a proprietary artificial-intelligence-based data processing engine, allowing for highly scalable and reproducible interrogation of glycoproteins with site- and glycan-specificity. Methods: Using this platform, we interrogated 519 glycopeptide (GP) biomarkers derived from 70 serum proteins in pre-treatment samples from a cohort of 103 individuals (56 females, 47 males, age ranging from 18 to 84 years) presenting with one of 20 solid cancer types. All patients were treated with durvalumab and tremelimumab immune checkpoint inhibitor (ICI) therapy. Median follow-up for overall survival (OS) was 11.4 months, with 70 events total observed. OS associations were assessed for individual GPs via Cox regression models and leave-one-out-cross-validation (LOOCV) was employed to generate penalized multivariable prediction scores. Notably, 43 patients had a primary diagnosis of bone and soft tissue sarcoma, and stratified analyses were carried out in this population. Results: We identified 154 biomarkers significantly associated with OS in the full dataset after adjusting for multiple comparisons (FDR &lt; 0.05). Of these, 7 were statistically significant at p &lt; 0.01 in the sarcoma-only subset. LOOCV models built in all cancer types resulted in held-out scores that discriminated those likely to exhibit long-term survival post-ICI therapy from those unlikely to benefit (HR = 4.0, p = 4.91E-08, with 4 GPs included in the final model). Furthermore, LOOCV models including only sarcoma patients demonstrated even stronger predictive attributes (HR = 8.22, p = 2.10E-05, employing 2 glycopeptides). All 9 sarcoma patients with extreme glycosylation signatures for prediction of poor survival displayed quick clinical progression with little benefit from ICI therapy. Relative signal strength and comparative analyses demonstrated strong histotype-specificity inherent in the biomarkers employed for sarcoma vs all cancers. Conclusions: Our results indicate that glycoproteomic liquid biopsy holds potential as a predictive biomarker for identifying sarcoma patients who will derive the greatest benefit from ICI therapy.

Maintenance olaparib in patients (pts) with platinum-sensitive relapsed ovarian cancer (PSROC) by somatic (s) or germline (g) BRCA and other homologous recombination repair (HRR) gene mutation status: Overall survival (OS) results from the ORZORA study.

5519 Background: In the SOLO2 (NCT01874353) trial, maintenance olaparib provided clinically meaningful improvement in OS for PSROC pts with a gBRCA mutation (m) compared with placebo (median 51.7 vs 38.8 months [mo], respectively). The ORZORA trial (NCT02476968) assessed efficacy and safety of maintenance olaparib in PSROC pts with a BRCAm (s or g) or a non-BRCA HRRm. Median progression-free survival (18.0 mo, BRCAm; 16.4, non-BRCA HRRm) was reported at primary data cutoff (DCO). We report final OS analyses. Methods: We conducted an open-label, single-arm, multicenter study of PSROC pts in response to platinum-based chemotherapy (PBC) after ≥2 prior lines of PBC. Pts underwent prospective central screening for tumor BRCAm status (myChoice CDx, Myriad Genetic Laboratories, Inc.), then central gBRCAm testing (BRACAnalysis CDx, Myriad Genetic Laboratories, Inc.) to determine s or g status. An exploratory cohort comprised of pts with predefined non-BRCA HRRm (FoundationOne CDx, Foundation Medicine, Inc.). Pts received maintenance olaparib (400 mg bid; capsules) until progression. OS and time to second progression (PFS2) were secondary endpoints. Results: 181 pts were enrolled (BRCAm n = 145 [s, n = 55; g, n = 87; s/g status unknown, n = 3]; non-BRCA HRRm, n = 33; unassigned, n = 3). At DCO (June 25, 2021), median OS follow-up in censored pts was 42.6 mo in BRCAm and 39.3 mo in non-BRCA HRRm pts. OS and PFS2 are reported in the Table. PBC was received as a subsequent therapy by 33.1% BRCAm, 32.7% sBRCAm, 33.3% gBRCAm, and 45.5% non-BRCA HRRm pts. 177 pts received ≥1 dose of olaparib and were included in safety analyses; 6.2% of pts discontinued because of adverse events (AEs). 37.9% of pts reported grade ≥3 AEs, the most common being anemia (16.4%). Since primary DCO, one new primary malignancy and four myelodysplastic syndrome events occurred. Conclusions: In final OS analyses, maintenance olaparib capsules showed consistent clinical activity in BRCAm and sBRCAm PSROC pts. Exploratory analyses suggest similar activity in non-BRCA HRRm pts. No new safety signals were observed. Findings highlight that PSROC pts, beyond those with a gBRCAm, can benefit from maintenance olaparib. Clinical trial information: NCT02476968. [Table: see text]

Differences in treatment and survival of older patients with operable breast cancer between the United Kingdom and the Netherlands – A comparison of two national prospective longitudinal multi-centre cohort studies

BackgroundPrevious studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been hypothesised that these differences in survival outcomes could be related to treatment variation. ObjectivesWe aimed to compare patient and tumour characteristics, treatment selection and survival outcomes between two large prospective cohorts of older patients with operable breast cancer from the United Kingdom (UK) and The Netherlands. MethodsWomen diagnosed with operable breast cancer aged ≥70 years were included. A baseline comprehensive geriatric assessment was performed in both cohorts, with data collected on age, comorbidities, cognition, nutritional and functional status. Baseline tumour characteristics and treatment type were collected. Univariable and multivariable Cox regression models were used to compare overall survival between the cohorts. Results3262 patients from the UK Age Gap cohort and 618 patients from the Dutch Climb cohort were included, with median ages of 77.0 (IQR: 72.0–81.0) and 75.0 (IQR: 72.0–81.0) years, respectively. The cohorts were generally comparable, with slight differences in rates of comorbidity and frailty. Median follow-up for overall survival was 4.1 years (IQR 2.9–5.4) in Age Gap and 4.3 years (IQR 2.9–5.5) in Climb. In Age Gap, both the rates of primary endocrine therapy and adjuvant hormonal therapy after surgery were approximately twice those in Climb (16.6% versus 7.3%, p < 0.001 for primary endocrine therapy, and 62.2% versus 38.8%, p < 0.001 for adjuvant hormonal therapy). There was no evidence of a difference in overall survival between the cohorts (adjusted HR 0.94, 95% CI 0.74–1.17, p = 0.568). ConclusionsIn contrast to previous studies, this comparison of two large national prospective longitudinal multi-centre cohort studies demonstrated comparable survival outcomes between older patients with breast cancer treated in the UK and The Netherlands, despite differences in treatment allocation.