Absence Of Visceral Metastases Research Articles

Targeted Radionuclide Therapy for the Treatment of Metastatic Bone Disease: A Retrospective Analysis in Moscow, Russia

Introduction: Metastatic bone disease (MBD) is a common complication of advanced cancer, causing significant morbidity and negatively impacting patients' quality of life. Targeted radionuclide therapy (TRT) has emerged as a promising treatment modality for MBD, offering targeted delivery of therapeutic radiation to bone metastases while minimizing damage to healthy tissues. Methods: A retrospective cohort study was conducted at leading oncology centers in Moscow, Russia, between 2018 and 2023. Patients with MBD who received TRT with either Strontium-89 or Samarium-153 were included. Data on patient demographics, primary tumor type, number of bone metastases, pre-treatment pain scores, performance status, and survival outcomes were collected. Results: A total of 150 patients were included in the study (mean age 62 years, 55% female). The most common primary tumor types were prostate (35%), breast (25%), and lung (15%). The median number of bone metastases was 5 (range 1-20). Pre-treatment pain scores were high (median 7 on a 0-10 scale). A significant reduction in pain scores was observed post-TRT (median 3, p<0.001). Overall survival at 1 year was 75%, with a median survival of 18 months. Favorable prognostic factors included a lower number of bone metastases, good performance status, and absence of visceral metastases. Conclusion: TRT is a safe and effective treatment option for patients with MBD in Moscow, Russia, offering significant pain palliation and improved quality of life.

Efficacy and safety of everolimus plus exemestane in patients with hormone receptor-positive, HER-2-negative advanced breast cancer: Results from the open-label, multicentre, non-interventional BRAWO study.

BRAWO, a real-world study, assessed the efficacy, quality of life (QoL) and safety of EVE + EXE in postmenopausal women with HR+/HER2- advanced breast cancer (ABC) in routine clinical practice. Postmenopausal women with HR+/HER2-ABC with recurrence or progression after a NSAI were included. Primary Observation parameters included the evaluation of the effectiveness of EVE + EXE. A multivariate-analysis using Cox proportional hazard model was built to identify predictors of progression. Overall, 2100 patients were enrolled (August 2012-December 2017); 2074 were evaluable for efficacy and safety analyses. Majority of patients (60.6%) received EVE + EXE as first (28.7%) or second-line (31.9%) therapy. Visceral metastases were present in 54.1% patients. Median progression-free survival (mPFS) reported as 6.6 months (95%CI: 6.3-7.0). Multivariate-analysis in a subset of patients (n = 1837) found higher body mass index (BMI) and non-visceral metastases to be independent predictors of favorable PFS. Patients with a BMI of 20 to <25 had a mPFS of 6.0 (95%CI: 5.4-6.4) and those with a BMI ≥30 had mPFS of 8.5 (95%CI: 6.9-9.9). 41.2% patients achieved stable disease and 7.3% partial response. No major changes were observed QoL; 86.4% patients received stomatitis prophylaxis and 41.4% experienced EVE related AEs of stomatitis, mainly low grade. AEs occurred in 91.2% of patients, of which stomatitis (42.6%) and fatigue (19.8%) were most frequent. The BRAWO study provides real-world evidence of efficacy and safety of EVE + EXE in patients with HR+, HER2- ABC. A high BMI and the absence of visceral metastases were independent predictors of PFS in this cohort of patients.

MAIN-CAV: Phase III randomized trial of maintenance cabozantinib (CABO) and avelumab (Av) vs Av after first-line platinum-based chemotherapy in patients (pts) with metastatic urothelial cancer (mUC; Alliance A032001).

TPS714 Background: 1st-line induction platinum-based chemotherapy followed by switch maintenance Av is the current preferred standard of care in patients (pts) with aUC who do not progress after platinum-based chemotherapy. There is an significant need to further improve outcomes by combining Av with an effective, non-cross resistant therapy with non-overlapping toxicity. CABO is an oral inhibitor of MET, VEGFR and TAM family receptors involved in tumor growth, angiogenesis and immune cell regulation and has shown efficacy in UC in combination with PD-1/PD-1L1 inhibitor. We hypothesized that CABO-Av combination would improve survival vs Av alone and have an acceptable safety profile as switch maintenance therapy in mUC. Methods: MAIN-CAV is a phase III randomized, multicenter, international trial for pts with locally advanced/metastatic UC (including cN3M0 only)) who do not progress after 4-6 cycles of any platinum-based chemotherapy (gem-cis, gem-carbo, MVAC or ddMVAC). 654 adults are randomized 1:1 within 3-10 weeks (wk) after last dose of chemotherapy to receive Av 800 mg IV every 2 wk or Av and CABO 40 mg daily for up to 2 yrs. Key eligibility criteria include ECOG PS 0-1, no prior use of anti-PD(L)1, no CNS metastases, no major surgery within 4 wks, no uncontrolled hypertension or cardiovascular disorders. Pts are stratified based on 1) best response to 1L chemotherapy: complete vs partial response vs stable disease and 2) presence vs absence of visceral metastases. The primary endpoint is overall survival (OS) with assumptions of 1-sided alpha 0.025, power 80%, median OS 21 months (mo) with Av and hazard ratio 0.75, thus hypothesizing median OS 28 mo on CABO-Av. Key secondary endpoints include progression-free survival, safety, tolerability, and efficacy of CABO-Av vs Av alone based on RECIST 1.1 and iRECIST criteria (and PD-L1 status).Quality of life (QOL) are assessed using EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, EORTC QLQ-BLM30 between pts on CABO-Av vs Av alone. Biomarkers of response and resistance to Av will be assessed using baseline archival tissues, baseline and serial blood, ctDNA, stool and urine. Imaging studies will test the correlation of established and new radiomic signatures with survival, adverse events and QOL and incorporate both radiologic and biologic features to assess their potential association with outcomes. This trial would be the first to systematically address whether adding the multitargeted TKI, CABO, to Av improves survival vs Av alone as 1L maintenance therapy. https://acknowledgments.alliancefound.org . Support: U10CA180821, U10CA180882; U24CA196171, U10CA180863 (CCTG); Clinical trial information: NCT05092958 .

Multi-Institutional Validation of the Recursive Partitioning Analysis for Overall Survival in Patients Undergoing Spine Radiosurgery for Spine Metastasis

The recently published spine radiosurgery (sSRS) recursive partitioning analysis (RPA) for overall survival (OS) separated patients into 3 distinct prognostic groups. We sought to externally validate this RPA using 3 separate multi-institutional datasets. A total of 444 patients were utilized to develop the recently published sSRS RPA predictive of OS in patients with spine metastases. The RPA identified three distinct prognostic classes. RPA Class 1 was defined as KPS >70 and controlled systemic disease (n = 142); RPA Class 2 was defined as KPS>70 with uncontrolled systemic disease or KPS ≤70, age ≥54 and absence of visceral metastases (n = 207); RPA Class 3 was defined as KPS ≤70 and age <54 years or KPS≤70, age ≥54 years and presence of visceral metastases (n = 95). We utilized data from 3 large tertiary care centers to independently validate this RPA. Data from each institution was utilized independently to validate the RPA to minimize confounding based on institutional differences in patient selection. A total of 1,184 patients (221 patients from institution A, 749 institution B, and 214 from institution C) were in the validation cohort and were divided based on their RPA Class. Kaplan-Meier method was used to estimate OS and log-rank test was used to compare OS between RPA classes. In each of the validation cohorts, the median OS was 19.9 months (institution A), 11.0 months (institution B), and 24.4 months (institution C). The patient distribution into RPA classification based on Institution A/B/C was, Class 1 (19.4%, 15.1%, 50.5%), Class 2 (74.7%, 57.7%%, 37.9%), and Class 3 (5.9%, 27.2%%, 11.2%), respectively. The median OS for patients in the validation cohort at Institution A/B/C based on RPA class was Class 1 (54 months, 27.1 months, 50.0 months), Class 2 (15.9 months, 13.0 months, 15.1 months) and Class 3 (6.9 months, 3.5 months, 6.1 months), respectively. Patients in RPA Class 1 had a significantly better OS compared to those in Class 2 of the each of the three external institution validation cohorts (p<0.01). Similarly, patients in RPA Class 2 had a significantly better OS compared to those in Class 3 (p<0.01). The external datasets from three large institutions independently validated the spine SRS RPA successfully for OS in patients undergoing sSRS for spinal metastases. This is the first RPA for OS to have been externally validated using multiple large datasets. Based on this validation, upfront spine SRS is strongly supported for patients in RPA Class 1 and Class 2 and is also cost effective with median OS >11 months for these patients. Patients in RPA Class 3 would benefit most from upfront conventional radiotherapy given their poor expected survival. Given successful external validation, this RPA helps guide physicians to identify those patients with spinal metastases who most benefit from sSRS.

Pertuzumab retreatment in patients with HER2-positive locally advanced/metastatic breast cancer: Overall survival results of a phase III randomized trial (JBCRG-M05: PRECIOUS).

1015 Background: We previously reported that pertuzumab (P) retreatment in combination with trastuzumab (T) + chemotherapy based on physician’s choice (C) (PTC) significantly improved investigator-assessed progression-free survival (PFS) compared with T + C (TC) in patients with HER2-positive locally advanced/metastatic breast cancer (LA/MBC) previously treated with P-containing regimens in the phase III PRECIOUS study. Here we report updated OS at the median follow-up of 27.4 mo. Methods: Patients previously treated with P-containing regimens as 1st/2nd-line treatment for LA/MBC were randomly assigned 1:1 to two groups, PTC group and TC group, stratified by estrogen receptor (ER) status, previous treatment duration of P, number of previous chemotherapy regimens, and presence or absence of visceral metastasis. The primary endpoint was investigator-assessed PFS. The key secondary endpoints included OS, independent reviewer assessed PFS and safety. Superiority of PTC to TC will be tested using a log-rank test and a one-sided P-value of less than 0.05 will be considered an indicator of superiority. The distribution of OS will be estimated using the Kaplan-Meier method. In addition, the hazard ratio and one-sided 95% CI of the therapeutic effect between the groups will be calculated using the Cox proportional hazard model. Results: Of the 219pts enrolled, 217 (108 PTC, 109 TC) were included in the intent-to-treat analysis. At the data cutoff (Dec 31, 2021), OS and PFS events were 138 (63.6%) and 190 (87.6%), respectively. Updated median OS was significantly longer in the PTC group (median OS 36.2 vs. 26.5 mo.; HR = 0.73 [one side 95%CI upper limit, 0.97]; log-rank test p = 0.0323). In a prespecified subgroup analysis for OS including ER, visceral metastases, number of previous chemotherapy regimen was broadly constant without disease-free interval. Updated median investigator-assessed PFS (5.5 vs. 4.2 mo.; HR = 0.81 [one side 95%CI upper limit, 1.03]; stratified log-rank test p = 0.019) were also significantly better in the PTC group. Median PFS by independent review did not show the difference between two groups (4.4 vs. 4.4 mo.; HR = 1.03 [one side 95%CI upper limit, 1.36]; log-rank test p = 0.561). The serious adverse event rate did not differ between the groups (19.0% vs. 23.1%). There were no new safety signals in the two groups. Conclusions: Retreatment of P in combination with TC demonstrated significantly improved OS compared to TC. HER2 dual blockade with PT can contribute to improve survival in patients previously treated with P-containing regimens as 1st/2nd-line treatment for LA/MBC. Clinical trial information: NCT02514681 .

MAIN-CAV: Phase III randomized trial of maintenance cabozantinib and avelumab versus avelumab after first-line platinum-based chemotherapy in patients (pts) with metastatic urothelial cancer (mUC; Alliance A032001).

TPS4609 Background: First-line platinum-based chemotherapy followed by maintenance avelumab (Av) is the current preferred standard of care in patients (pts) with mUC who do not progress after platinum-based chemotherapy. There is an unmet need to further improve outcomes by combining Av with an effective, non-cross resistant therapy with non-overlapping toxicity. CABO is an oral inhibitor of MET, VEGFR and TAM family receptors involved in tumor growth, angiogenesis and immune cell regulation and has shown efficacy in UC in combination with PD-1/PD-1L1 inhibitors. We hypothesize that CABO-Av combination will be synergistic in pts with mUC with an acceptable safety profile and will improve upon the benefit seen with Av maintenance in mUC. Methods: MAIN-CAV is a phase III randomized, multicenter, international trial for locally advanced/mUC pts (including N3 only disease) who do not progress after 4-6 cycles of any platinum-based chemotherapy (gem-cis, gem-carbo, MVAC or ddMVAC). 654 adult pts will be randomized 1:1 within 3-10 weeks (wk) after last dose of chemotherapy to receive Av 800 mg IV every 2 wk or combination of Av and CABO 40 mg orally daily for up to 2 yrs. Key eligibility criteria include ECOG PS 0-1, no prior use of immunotherapy (exception of BCG), no central nervous system metastases, no major surgery within 4 wk, no uncontrolled hypertension or cardiovascular disorders. Pts will be stratified based on 1) best response to 1L therapy: complete response vs partial response vs stable disease and 2) presence or absence of visceral metastases. The primary endpoint is overall survival (OS) with assumptions of one-sided alpha of 0.025, power of 80%, median OS of 21 months (mo) on Av arm and hazard ratio (HR) of 0.75, thus hypothesizing a median OS of 28 mo on CABO-Av combination arm. Key secondary endpoints include progression-free survival, safety, tolerability, and activity of CABO-Av compared to Av alone based on RECIST 1.1 and iRECIST criteria and PD-L1 status of pts’ tumors. Quality of life (QOL) will be assessed using EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, EORTC QLQ-BLM30 between pts on CABO-avelumab vs avelumab alone. Biomarkers of response and resistance to Av will be assessed using baseline archival tissues, baseline and serial blood, ctDNA, stool and urine. Imaging studies will test correlation of established and new radiomic signatures with OS, adverse events and QOL and incorporate both radiologic and biologic features to predict outcomes. This trial would be the first to systematically address whether adding a multitargeted TKI, CABO to Av leads to improved clinical outcomes compared to Av alone. Clinical trial information: NCT05092958 .

Multi-Institutional Datasets Validate the Recursive Partitioning Analysis for Overall Survival in Patients Undergoing Spine Radiosurgery for Spine Metastasis

<h3>Purpose/Objective(s)</h3> The recently published spine radiosurgery (sSRS) recursive partitioning analysis (RPA) for overall survival (OS) separated patients into 3 distinct prognostic groups. We sought to externally validate this RPA using a multi-institutional dataset. <h3>Materials/Methods</h3> A total of 444 patients were utilized to develop the recently published sSRS RPA predictive of OS in patients with spine metastases. The RPA identified three distinct prognostic classes. RPA Class 1 was defined as KPS >70 and controlled systemic disease (n=142); RPA Class 2 was defined as KPS>70 with uncontrolled systemic disease or KPS ≤70, age ≥54 and absence of visceral metastases (n=207); RPA Class 3 was defined as KPS ≤70 and age <54 years or KPS≤70, age ≥54 years and presence of visceral metastases (n=95). We utilized data from large tertiary care centers to validate this RPA. A total of 749 patients were in the validation cohort and were divided based on their RPA Class. Kaplan-Meier method was used to estimate OS and log-rank test was used to compare OS between RPA classes. <h3>Results</h3> In the validation cohort (749 patients), the median OS was 11.0 months. One-hundred-thirteen (15.1%) patients were in RPA Class 1, 432 (57.7%) patients in RPA Class 2 and 204 (27.2%) patients in RPA Class 3. The median OS in the validation cohort based on RPA Class was 27.1 months for Class 1, 13.0 months for Class 2 and 3.5 months for Class 3. Patients in RPA Class 1 had a significantly better OS compared to those in Class 2 of the validation cohort (p<0.01). Similarly, patients in RPA Class 2 had a significantly better OS compared to those in Class 3 (p<0.01). <h3>Conclusion</h3> The external datasets from two large centers validated the spine SRS RPA successfully for RPA for OS for patients undergoing sSRS for spinal metastases. This is the first RPA for OS to have been externally validated using a large dataset. Based on this validation, upfront spine SRS is strongly supported for patients in RPA Class 1. Upfront SRS is also supported for RPA Class 2 patients. Patients in RPA Class 3 would benefit most from upfront conventional radiotherapy given their poor expected survival. Given successful external validation, this RPA helps guide physicians to identify those patients with spinal metastases who most benefit from sSRS.

Clear Cell Renal Cell Carcinoma Spinal Metastases: Which Factors Matter to the Overall Survival? A 10-Year Experience of a High-Volume Tumor Spine Center.

: BackgroundClear cell renal cell carcinoma (ccRCC) usually spreads in the spinal region causing instability or spinal cord compression leading to neurological deficits. Therefore, surgical treatment is required for improving the outcome of patients. The aim of this study is to identify which prognostic factors could affect overall survival in patients affected by ccRCC. Methods: Retrospective cohort study of patients with ccRCC spinal metastases, surgically treated from November 2009 to April 2019. Demographic and clinical data were collected. The Kaplan–Meier method was used to estimate overall survival, and the log-rank test was used to evaluate differences in survival among potentially prognostic factors. Results: A total of 69 patients were surgically treated and followed up for a median period of 65 months. The average age at the time of surgery was 62.6 years old. The median overall survival (OS) was 34.7 months (95% CI 20.8–51.9) and 5-year OS was 31.2% (95% CI 19.2–44.1). A high Tokuhashi score (p = 0.0217), the presence of visceral metastases (p < 0.001), other bone metastases (p = 0.02012) and the kind of surgical treatment (p = 0.0395) are the main prognostic factors that influence the OS. Moreover, 3-year progression-free survival (PFS) was analyzed: the median PFS was 53.1 months and the % 3-year PFS was 62.9% (45.2–76.3). In the multivariate analysis, only pre-operative radiation therapy had a significant impact on 3-year PFS (95% CI 0.929–12.994, p = 0.0643). Conclusion: The results of this study suggest that the absence of visceral metastases and an aggressive surgery as en-bloc, when feasible, could prolong the survival rate and improve quality of life for patients.

223Ra-Dichloride Therapy.

223Ra-dichloride (Xofigo; Bayer) is an α-emitting radioactive agent used to treat symptomatic bone metastases in patients with castration-resistant prostate cancer in the absence of visceral metastases ([ 1 ][1]). It functions as a calcium analog and causes double-strand DNA breaks in tissue,

Efficacy of novel androgen axis inhibitors for the treatment of hormone-sensitive prostate cancer in patients with visceral metastases: a systematic review and meta-analysis

Background. The presence of visceral metastases (VM) is a significant adverse prognostic factor affecting the overall survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Recently, new drugs, such as novel antiandrogen therapies (NAT), have been introduced, expanding the options for the treatment of mHSPC.Aim. To assess whether presence or absence of VM at baseline affects risk of death in patients with mHSPC receiving NAT therapy in combination with androgen deprivation therapy (ADT) compared with standard therapy (ADT ± 1st generation antiandrogen).Search strategy. Bibliographic databases PubMed and Google Scholar were searched from inception through January 21, 2022.Selection criteria. Eligible studies were randomized clinical trials with parallel design in patients with mHSPC. Subgroups of patients with or without VM at baseline were required. The following drugs were chosen as interventional agents: abiraterone acetate, apalutamide, enzalutamide, darolutamide. All in addition to ADT. The main outcome was overall survival.Data analysis. We applied the inverse variance technique for the meta-analysis of hazard ratios (HR). In HR analysis we adopted a fixed-effect model.Results. The analysis included three randomized clinical trials with 3376 patients, of which a total of 485 (14.4 %) patients had VM. Compared with ADT, the risk of death in patients with VM treated with NAT + ADT (HR 0.69; 95 % confidence interval (CI) 0.53–0.89; n = 485; p = 0.004) was similar to the risk of death in patients without VM (HR 0.66; 95 % CI 0.59–0.75; n = 2461; p &lt;0.00001). The test for subgroup differences suggests that there is no statistically significant subgroup effect (χ2 = 0,05; df = 1; p = 0,82; I2 = 0 %). Ordered from the most to the least effective, treatments with improved overall survival in patients with VM when added to ADT included abiraterone acetate (HR 0.58; 95 % CI 0.41–0.82), apalutamide (HR 0.76; 95 % CI 0.47–1.23), enzalutamide (HR 1.05; 95 % CI 0.54–2.04). In patients without VM, the drugs are in the following order: enzalutamide (HR 0.62; 95 % CI 0.47–0.82), apalutamide (HR 0.65; 95 % CI 0.52–0.81), abiraterone acetate (HR 0.69; 95 % CI 0.58–0.82).Conclusion. Patients with mHSPC benefit from the combination of NAT with ADT, regardless of the presence or absence of VM (HR 0.67; 95 % CI 0.60–0.75; n = 2946; p &lt;0,00001). Abiraterone acetate has the greatest advantages in reducing the risk of death in patients with VM.

MAIN-CAV: Phase III randomized trial of maintenance cabozantinib and avelumab versus avelumab after first-line platinum-based chemotherapy in patients with metastatic urothelial cancer (mUC) (Alliance A032001).

TPS4607 Background: First-line platinum-based chemotherapy followed by maintenance avelumab (Av) is the current preferred standard of care in patients (pts) with mUC who do not progress after platinum-based chemotherapy. There is an unmet need to further improve outcomes by combining Av with an effective, non-cross resistant therapy with non-overlapping toxicity. Cabozantinib (CABO) is an oral inhibitor of MET, VEGFR and TAM family receptors involved in tumor growth, angiogenesis and immune cell regulation and has shown efficacy in UC in combination with PD-1/PD-1L1 inhibitors. We hypothesize that CABO-Av combination will be synergistic in pts with mUC with an acceptable safety profile and will improve upon the benefit seen with Av maintenance in mUC. Methods: MAIN-CAV is a phase III randomized, multicenter, international trial for locally advanced/mUC pts (including N3 only disease) who do not progress after 4-6 cycles of any platinum-based chemotherapy (gem-cis, gem-carbo, MVAC or ddMVAC). 654 adult pts will be randomized 1:1 within 3-10 weeks (wk) after last dose of chemotherapy to receive Av 800 mg IV every 2 wk or combination of Av and CABO 40 mg orally daily for up to 2 yrs. Key eligibility criteria include ECOG PS 0-1, no prior use of immunotherapy (exception of BCG), no central nervous system metastases, no major surgery within 4 wk, no uncontrolled hypertension or cardiovascular disorders. Pts will be stratified based on 1) best response to 1L therapy: complete response vs partial response vs stable disease and 2) presence or absence of visceral metastases. The primary endpoint is overall survival (OS) with assumptions of one-sided alpha of 0.025, power of 80%, median OS of 21 months (mo) on Av arm and hazard ratio (HR) of 0.75, thus hypothesizing a median OS of 28 mo on CABO-Av combination arm. Key secondary endpoints include progression-free survival, safety, tolerability, and activity of CABO-Av compared to Av alone based on RECIST 1.1 and iRECIST criteria and PD-L1 status of pts’ tumors. Quality of life (QOL) will be assessed using EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, EORTC QLQ-BLM30 between pts on CABO-avelumab vs avelumab alone. Biomarkers of response and resistance to Av will be assessed using baseline archival tissues, baseline and serial blood, ctDNA, stool and urine. Imaging studies will test correlation of established and new radiomic signatures with OS, adverse events and QOL and incorporate both radiologic and biologic features to predict outcomes. This trial would be the first to systematically address whether adding a multitargeted TKI, CABO to Av leads to improved clinical outcomes compared to Av alone. Support: U10CA180821, U10CA180882, U24CA196171,U10CA180863 (CCTG); Clinical trial information: NCT05092958.

Time on treatment with abiraterone and enzalutamide in the Patient-overview Prostate Cancer in The National Prostate Cancer Register of Sweden

Background There are little and inconsistent data from clinical practice on time on treatment with the androgen receptor-targeted drugs (ART) abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). We assessed time on treatment with ART and investigated predictors of time on treatment. Material and methods Time on treatment with ART in men with mCRPC in the patient-overview prostate cancer (PPC), a subregister of the National Prostate Cancer Register (NPCR) of Sweden, was assessed by use of Kaplan–Meier plots and Cox regression. To assess the representativity of PPC for time on treatment, a comparison was made with all men in NPCR who had a filling for ART in the Prescribed Drug Registry. Results 2038 men in PPC received ART between 2015 and 2019. Median time on treatment in chemo-naïve men was 10.8 (95% confidence interval 9.1–13.1) months for abiraterone and 14.1 (13.5–15.5) for enzalutamide. After the use of docetaxel, time on treatment was 8.2 (6.5–12.4) months for abiraterone and 11.1 (9.8–12.6) for enzalutamide. Predictors of a long time on treatment with ART were long duration of ADT prior to ART, low serum levels of PSA at start of ART, absence of visceral metastasis, good performance status, and no prior use of docetaxel. PPC captured 2522/6337 (40%) of all men in NPCR who had filled a prescription for ART. Based on fillings in the Prescribed Drug Registry, men in PPC had a slightly longer median time on treatment with ART compared to all men in NPCR, 9.6 (9.1–10.3) vs. 8.6 (6.3–9.1) months. Conclusions Time on treatment in clinical practice was similar or shorter than that in published RCTs, due to older age, poorer performance status and more comorbidities.

Efficacy of Fulvestrant in Women with Hormone-Resistant Metastatic Breast Cancer (mBC): A Canadian Province Experience

Simple SummaryFulvestrant is a medication that is approved as first and second-line treatment in patients with hormone receptor positive advanced breast cancer. In clinical practice, fulvestrant is still used beyond the second line of treatment. This study investigated the use of fulvestrant in a Saskatchewan population of women with advanced breast cancer. We found that fulvestrant is effective when used in both the early and later lines of treatment, although the benefit is more pronounced in the earlier line of therapy. Women with disease affecting their visceral organs such as lung, liver or peritoneum had decreased disease control and survival on fulvestrant. Women who had received chemotherapy after fulvestrant and had a clinical response to fulvestrant had better survival.Introduction: Fulvestrant has demonstrated efficacy in hormone receptor positive (HR+) metastatic breast cancer (mBC), both in first-and second-line settings. In clinical practice, however, fulvestrant has been used as a later-line therapy. This study assessed the efficacy of fulvestrant in women with mBC in early-versus later-line therapy. Methods: This retrospective cohort study assessed Saskatchewan women with HR+ mBC who received fulvestrant between 2003–2019. A multivariate Cox proportional survival analysis was performed. Results: One hundred and eighty-six women with a median age of 63.5 years were identified—178 (95.6%) had hormone-resistant mBC, 57.5% had visceral disease, and 43.0% had received chemotherapy before fulvestrant. 102 (54.8%) women received ≤2-line-therapy, and 84 (45.2%) received ≥3 line-therapy before fulvestrant. The median time to progression (TTP) was 12 months in the early-treatment vs. 6 months in the later-treatment group, p = 0.015. Overall survival (OS) from the start of fulvestrant was 26 months in the early-treatment group vs. 16 months in the later-treatment group, p = 0.067. On multivariate analysis, absence of visceral metastasis, HR: 0.70 (0.50–0.99), was significantly correlated with better TTP, whereas post-fulvestrant chemotherapy, HR: 0.32 (0.23–0.47), clinical benefit from fulvestrant, HR: 0.44 (0.30–0.65), and absence of visceral metastasis, HR: 0.70 (0.50–0.97), were correlated with better OS. Conclusions: Fulvestrant has demonstrated efficacy as both early-and later-line therapy in hormone-resistant mBC. Our results show that women with clinical benefit from fulvestrant, who received post-fulvestrant chemotherapy, or had non-visceral disease, had better survival.

Clinical Characteristics and Prognosis of Renal Cell Carcinoma With Spinal Bone Metastases.

BackgroundThe prognosis of renal cell carcinoma (RCC) with spinal bone metastasis (sBM) varies greatly. In this study, we aimed to define the clinical characteristics and prognostic factors of RCC with spinal bone metastasis (sBM) in our center.MethodsThe clinical and medical records of RCC patients with sBMs were collected. The gender, age, time of BM, the extent of BM, the number of BMs, the presence or absence of visceral metastasis, and the pathological type of BM were investigated. All patients were followed up regularly. Overall survival (OS) was calculated from the date of BMs diagnosis to death or last follow-up using Kaplan-Meier method and modelled with Cox regression analysis.ResultsForty-three RCC patients with sBM were collected. sBM was found synchronously in 30 patients (70%) and metachronously in 13 patients (30%). The median survival time was 30 months in 13 patients (30%) with solitary sBM and 19 months in 30 patients (70%) with multiple sBMs (P = 0.002). Visceral metastasis occurred in 12 patients (28%) with the median survival time of 17 months, while the other 31 patients (72%) had no visceral metastasis with the median survival time of 29 months (P<0.001). En-block resection was done in 10 patients with median survival time of 40.1 months. Non-en-block resection were done in 33 patients with median survival time of 19.7 months (P<0.001). Multivariate COX regression analysis showed that MSKCC score, number of BM, visceral metastasis, and en-block resection are the independent prognosis factors of RCC patients with sBM.ConclusionsMSKCC risk stratification, number of sBM, visceral metastasis and en-block resection are significant prognostic factors for OS in RCC patients with spinal BM. Therefore, for selected patients who has solitary spinal BM with no visceral metastasis, en-block resection of spinal BM can potentially prolong survival and is the treatment of choice.

P0863 - Time on treatment with abiraterone and enzalutamide in the patient-overview prostate cancer in the national prostate cancer register of Sweden

Background There are little and inconsistent data from clinical practice on time on treatment with the androgen receptor-targeted drugs (ART) abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). We assessed time on treatment with ART and investigated predictors of time on treatment. Material and methods Time on treatment with ART in men with mCRPC in the patient-overview prostate cancer (PPC), a subregister of the National Prostate Cancer Register (NPCR) of Sweden, was assessed by use of Kaplan-Meier plots and Cox regression. To assess the representativity of PPC for time on treatment, a comparison was made with all men in NPCR who had a filling for ART in the Prescribed Drug Registry. Results 2038 men in PPC received ART between 2015 and 2019. Median time on treatment in chemo-naive men was 10.8 (95% confidence interval 9.1-13.1) months for abiraterone and 14.1 (13.5-15.5) for enzalutamide. After the use of docetaxel, time on treatment was 8.2 (6.5-12.4) months for abiraterone and 11.1 (9.8-12.6) for enzalutamide. Predictors of a long time on treatment with ART were long duration of ADT prior to ART, low serum levels of PSA at start of ART, absence of visceral metastasis, good performance status, and no prior use of docetaxel. PPC captured 2522/6337 (40%) of all men in NPCR who had filled a prescription for ART. Based on fillings in the Prescribed Drug Registry, men in PPC had a slightly longer median time on treatment with ART compared to all men in NPCR, 9.6 (9.1-10.3) vs. 8.6 (6.3-9.1) months. Conclusions Time on treatment in clinical practice was similar or shorter than that in published RCTs, due to older age, poorer performance status and more comorbidities.

Real-world outcomes from the systemic use of CDK 4/6 inhibitors (CDKIs) in the management of ER positive (+) HER2 negative (-) metastatic breast cancer (mBC).

e13031 Background: The use of CDKIs have transformed the management of ER+HER2- mBC. As the real-world data matures, this project describes patterns in response to systemic therapy that may inform treatment planning and prognostication. Methods: We analysed the ER+HER2- mBC dataset at Nottingham University Hospitals NHS Trust (NUH) generated by reviewing clinical notes, radiology and e-prescribing records to collect clinical data on patients treated with CDKIs between 01/10/2016 - 01/10/2020. Results: 272 patients with a median age of 65 years (30-90 years) were treated with CDKIs (palbociclib 54.0% (n=147); ribociclib 19.5% (n=53); abemaciclib 26.5% (n=72)) in combination with endocrine therapies (letrozole, anastrozole, exemestane and, fulvestrant). Median overall survival was 49.5 months. Treatment with first-line CDKIs (69.8%; n=190) resulted in superior PFS when compared to CDKIs in a ≥ second-line setting (30.2%; n=82) i.e., mPFS 21.3 vs 12.2 months (HR 0.67; 95% CI, 0.47-0.96; P=0.02). Univariate analysis shown in the table below indicates the benefit to PFS from presentations with de novo mBC and the absence of visceral metastases. In patients treated curatively for early breast cancer (EBC), better outcomes were demonstrated in patients presenting with mBC, &gt;12 months versus ≤12 months of completion of adjuvant endocrine therapy i.e., mPFS 28.4 vs 12.1 months (HR 0.50; 95% CI, 0.30-0.84; P=0.004) when treated with first-line CDKIs. A multivariate analysis identified benefit to PFS from first-line therapy with CDKIs (HR 0.70; 95% CI, 0.49-1.01; P=0.05) and presentation with de novo mBC (HR 0.56; 95% CI, 0.37-0.85; P=0.006). The presence of visceral metastases was associated with poorer outcomes (HR 1.52; 95% CI, 1.08-2.15; P=0.01). Conclusions: This analysis confirms the PFS benefit from CDKIs demonstrated in clinical trials is mirrored in the real-world setting. The analysis was not powered to delineate survival benefit between the individual CDKIs. Presentations with mBC following a prior history of EBC, within ≤12 months of completion of adjuvant endocrine therapy, and with visceral metastases may help predict poorer clinical outcomes and may need to be considered when prognosticating and in treatment planning. This analysis is hypotheses-generating and we will confirm our findings in a prospective manner as the dataset is expanded.[Table: see text]

Final results from ACIS, a randomized, placebo (PBO)-controlled double-blind phase 3 study of apalutamide (APA) and abiraterone acetate plus prednisone (AAP) versus AAP in patients (pts) with chemo-naive metastatic castration-resistant prostate cancer (mCRPC).

9 Background: As mCRPC is driven by activated androgen receptors and elevated intratumoral androgens, androgen annihilation may require dual inhibition. APA and AA are approved prostate cancer therapies that have distinct receptor inhibition and ligand suppression actions, respectively. ACIS compared radiographic progression-free survival (rPFS) of APA + AAP vs PBO + AAP in chemo-naive mCRPC. Methods: mCRPC pts with ongoing androgen deprivation therapy (ADT) but no other life-prolonging treatment since diagnosis were randomized 1:1 to APA (240 mg po QD) + AA (1000 mg po QD) + P (5 mg po BID) or PBO + AAP (stratified by presence or absence of visceral metastases, Eastern Cooperative Oncology Group performance status 0 or 1, and geographic region). The primary end point was rPFS (investigator assessed; defined from randomization date to radiographic progression date or death). Secondary/other end points included prostate-specific antigen (PSA) response, overall survival (OS), safety, time to PSA progression, chronic opioid use, initiation of cytotoxic chemotherapy, and pain progression. Results: 982 pts were enrolled (Dec 2014 to Aug 2016). Median rPFS was extended 6 mos with APA + AAP (22.6 mos) vs AAP (16.6 mos) (HR 0.69 [95% CI 0.58-0.83]; p &lt; 0.0001) at the final analysis for rPFS, coinciding with the first interim analysis of OS (median follow-up time 25.7 mo). At final analysis, treatment with APA + AAP vs AAP showed a significantly higher rate of confirmed ≥ 50% PSA decline. Although not statistically significant, treatment with APA + AAP vs AAP showed a longer median OS. Time to PSA progression, chronic opioid use, initiation of cytotoxic chemotherapy, and pain progression did not differ statistically significantly between arms. The safety profile was consistent with prior drug experience, with no new safety concerns. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 63.3% (310/490) of APA + AAP–treated pts vs 56.2% (275/489) of AAP-treated pts, with more grade 3 (56.1%, 275/490 vs 45.6%, 223/489) and less grade 4 (7.1%, 35/490 vs 10.6%, 52/489) TEAEs, respectively. Results based on biomarker subpopulations and quality of life will be presented. Conclusions: The ACIS final analysis met the primary end point and demonstrated a 31% reduction in risk of radiographic progression or death in chemo-naive mCRPC pts treated with the combination of APA + AAP with ADT vs AAP with ADT. Funding: Janssen Research &amp; Development. Trial registration: NCT02257736. Clinical trial information: NCT02257736. [Table: see text]

Abstract PD3-11: A randomized, open-label, phase III trial of pertuzumab re-treatment in HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab, trastuzumab, and chemotherapy: The Japan Breast Cancer Research Group-M05 (PRECIOUS) study

Abstract Background: Patients (pts) with HER2-positive locallyadvanced/metastatic breast cancer (LA/MBC) previously treated with pertuzumab(P)-containing regimens have few therapeutic options. The efficacy of Pre-treatment combined with trastuzumab (T)+chemotherapy as 3 or 4 -line chemotherapy was examined in such pts. Methods: Pts previously treated with P-containing regimens as1st/2nd-line treatment for LA/MBC were randomly assigned 1:1 to two groups(P+T+chemotherapy based on physicians’ choice (C) (PTC), and T+C (TC)),stratified by estrogen receptor status, previous P treatment duration, numberof previous chemotherapy regimens, and presence or absence of visceralmetastasis. The primary endpoint was investigator-assessed progression-freesurvival (PFS). Superiority of PTC to TC will be tested using a stratifiedlog-rank test that accounts for all stratification factors, and a one-sidedP-value of less than 0.05 will be considered an indicator of superiority. Thedistribution of PFS will be estimated using the Kaplan-Meier method. In addition,the hazard ratio and one-sided 95% CI of the therapeutic effect between thegroups will be calculated using the Cox proportional hazard model. Secondaryendpoints included independent reviewer assessed PFS, PFS in pts treated withT-DM1 as the latest regimen (PFS after T-DM1), objective response rate (ORR),overall survival (OS), safety, and health-related quality of life (HR-QoL). Results: Of the 219 pts enrolled, 217 (108 PTC, 109 TC) wereincluded in the intent-to-treat analysis. At the data cutoff (July 31, 2019),PFS and OS events were 184 (84.8%) and 84 (38.7%), respectively. Medianfollow-up time was 14.2 months (mo). Investigator-assessed PFS wassignificantly better in the PTC group (median PFS 5.3 vs. 4.2 mo; HR = 0.755[One-sided 95%CI upper limit, 0.967]; One-sided stratified log-rank test p =0.0217). Median PFS after T-DM1 (5.3 vs. 4.2 mo; HR = 0.801 [One-sided 95%CIupper limit, 1.061]; One-sided log-rank test p = 0.0952) and OS (28.8 vs. 23.4mo; HR = 0.713, [One-sided 95%CI upper limit, 1.026], One-sided log-rank test p= 0.062) tended to be longer in the PTC group, though further follow-up isneeded. The ORR with measurable disease (PTC (n = 90) 18.9% vs. TC (n = 92)19.6%) did not differ between the groups. The serious adverse event rate didnot differ between the groups (17.9% vs. 21.3%). There were no new safetysignals included cardiac events in the groups. In the comparison of HR-QoL bytime to deterioration analysis, there was no significant difference between thegroups in FACT-B trial outcome index (PTC 2.8 mo vs. TC 4.3 mo; HR = 1.274,log-rank test p = 0.2289).Conclusions: P re-treatment as 3 or 4 -line chemotherapy wasactive and feasible. P re-treatment can be a standard treatment option forpatients with HER2-positive LA/MBC previously treated with P.(ClinicalTrials.gov number: NCT02514681) Citation Format: Yutaka Yamamoto, Hiroji Iwata, Taira Naruto, Norikazu Masuda, Masato Takahashi, Tetsuhiro Yoshinami, Takayuki Ueno, Tatsuya Toyama, Takashi Yamanaka, Toshimi Takano, Masahiro Kashiwaba, Koichiro Tsugawa, Yoshie Hasegawa, Kenji Tamura, Hiroshi Tada, Fumikata Hara, Shigehira Saji, Satoshi Morita, Masakazu Toi, Shinji Ohno, Japan Breast Cancer Research Group. A randomized, open-label, phase III trial of pertuzumab re-treatment in HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab, trastuzumab, and chemotherapy: The Japan Breast Cancer Research Group-M05 (PRECIOUS) study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD3-11.

Impact of radiotherapy to the primary tumor on the efficacy of pembrolizumab for patients with advanced urothelial cancer: A preliminary study.

Radiotherapy plus immune checkpoint inhibitors can potentially induce synergistic antitumor immune responses. However, little clinical evidence is established regarding their combination therapy. Here, we aimed to assess whether radiotherapy to the primary tumor impacts on the efficacy of pembrolizumab in advanced urothelial cancer. We retrospectively reviewed 98 advanced urothelial cancer patients receiving pembrolizumab in a second‐ or later‐line setting using our multicenter cohort. Patients were categorized according to a history of radiotherapy to the primary tumor: patients previously exposed to radiotherapy to the primary tumor (Radiotherapy group, 17 patients [17%]) and those not (Nonradiotherapy group, 81 patients [83%]). The associations of radiotherapy to the primary tumor with objective response and survival were evaluated. The Radiotherapy group showed a significantly higher objective response ratio than did the Non‐radiotherapy group (65% vs 19%; P < .001). The Radiotherapy group had a higher progression‐free survival rate compared with the Nonradiotherapy group (52% vs 28% at 12 months; P = .078), but statistical significance was not reached. The Radiotherapy group had a significantly higher overall survival rate compared with the Non‐radiotherapy group (77% vs 50% at 12 months; P = .025). From multivariate analysis, radiotherapy to the primary tumor was an independent predictor for longer overall survival (hazard ratio, 0.31; P = .032) along with Eastern Cooperative Oncology Group performance status ≤1 and the absence of visceral metastasis. Therefore, radiotherapy to the primary tumor may enhance the efficacy of pembrolizumab for patients with advanced urothelial cancer.

Oncological Outcome of Combining Cytoreductive Prostatectomy and Metastasis-Directed Radiotherapy in Patients with Prostate Cancer and Bone Oligometastases: A Retrospective Cohort Study.

BackgroundThe current standard of care for metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to evaluate the efficacy and safety of a multimodal approach including local primary tumor therapy, metastasis-directed therapy (MDT), and hormonal therapy in patients with oligometastatic prostate cancer (PCa).MethodsWe reviewed data of patients with PCa and bone oligometastases at diagnosis treated in three institutions with ADT followed by cytoreductive surgery with or without metastases-directed radiotherapy. Oligometastases were defined as the presence of five or fewer metastatic lesions with the absence of visceral metastases. In this retrospective cohort study, 58 patients underwent cytoreductive radical prostatectomy and ADT. Of these, 26 patients (45%) received stereotactic body radiation therapy (SBRT) to all metastatic sites as a MDT. Oncological outcomes were analyzed using the Kaplan–Meier method.ResultsThe median follow-up period was 46.2 months. Of the 58 patients, the 3-year castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival was 75.9% and 91.4%, respectively. Pre- or post-treatment predictive factors for progression to CRPC, including prostate-specific antigen (PSA) level at diagnosis ≥20 ng/mL, Gleason grade groups 5, clinical T stage cT3b-4, PSA nadir level of ≥0.05 ng/mL, and no MDT with SBRT, were significantly associated with progression to CRPC. Subgroup analysis showed that the MDT group had significantly better CRPC-free survival than the non-MDT group with Gleason grade groups 1–4 (HR=0.228; 95% CI= 0.056–0.926). A total of 3.4% of the patients had grade 2 acute genitourinary toxicities and 5.2% had grade 2 acute gastrointestinal toxicities. No late grade >2 adverse events were observed.ConclusionThis multi-center, retrospective cohort study revealed the feasibility of combining cytoreductive prostatectomy and metastasis-directed radiotherapy for newly-diagnosed oligometastatic PCa. This treatment strategy has the potential to delay the progression to CRPC.