Subsequent Systemic Treatment Research Articles

Stereotactic body radiation therapy is beneficial for a subgroup of patients with urothelial cancer and solitary metastatic disease: a single institution real-world experience

BackgroundStandard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates, and targeted therapy. Oligometastatic disease (OMD) may be an intermediate state between localized and generalized cancer. The best treatment strategy for OMD and oligoprogressive (OPD) disease is poorly studied in mUC but local stereotactic body radiation therapy (SBRT) could be an option to avoid or delay systemic treatment. The aim of this study was to assess the efficacy and feasibility of SBRT given in a real-world patient population.MethodsAll patients with mUC treated with SBRT at Karolinska University Hospital, Stockholm, Sweden between 2009 and 2022 were included in this study. Baseline clinical characteristics, treatment data, SBRT dosimetry data and treatment outcome were collected retrospectively. The study endpoints were local control rate (LCR), progression-free-survival (PFS), overall survival (OS) and feasibility of SBRT.ResultsIn total 39 patients were treated with SBRT. The median follow-up was 25.6 months. The LCR was 82%. PFS and OS were 4.1 and 26.2 months, respectively. Treatment was well tolerated; all patients but one (treatment related pain) completed the planned SBRT. Number of metastases irradiated with SBRT was significantly associated with outcome; patients with only one irradiated lesion had more favourable PFS compared to individuals with 2 or more metastases (HR 4.12, 95% CI: 1.81–9.38, p = 0.001). A subgroup of patients (15%) achieved a sustained long-term survival benefit and never required systemic treatments after SBRT.ConclusionsSBRT was well tolerated and associated with high LCR. A subpopulation of patients with single metastatic lesion achieved long-term OS and never required subsequent systemic treatment after SBRT. Prospective randomized studies are warranted to discover treatment predictive biomarkers and to investigate the role of SBRT in oligometastatic UC.

Efficacy of immunotherapy retreatment in patients with non-small cell lung cancer receiving consolidative durvalumab.

8625 Background: The standard of care for patients with stage III, unresectable non-small cell lung cancer (NSCLC) is curative intent chemoradiation followed by durvalumab consolidation. However, most patients progress necessitating further treatment. Although immunotherapy (IO) is the cornerstone of treatment in advanced/metastatic disease, the benefit in patients who received prior durvalumab is unclear. Clinical trials excluded prior IO exposure and current guidelines do not provide specific recommendations. This study aims to characterize the efficacy of post-durvalumab IO treatment. Methods: This was a retrospective cohort study conducted at the University of North Carolina (UNC) Medical Center. Adult patients with unresectable NSCLC who received chemoradiation and consolidative durvalumab followed by subsequent systemic therapy for disease progression between February 2018 to May 2023 were included. Patients were excluded if they received targeted therapy as subsequent systemic treatment. The primary endpoint was real-world progression-free survival (rwPFS) of post-durvalumab treatment. Key secondary outcomes included physician assessed response, overall survival (OS), and subgroup analyses to identify biomarkers which may predict benefit from IO retreatment. Results: A total of 66 patients met inclusion criteria, of which 39 (59%) received subsequent chemotherapy alone and 27 (41%) received IO-containing therapy. Of those who received IO-containing treatments, 18 received chemotherapy plus IO (chemoIO) and 9 received IO alone. Durvalumab was discontinued for therapy completion (chemotherapy: 18%, IO: 26%), disease progression (chemotherapy: 54%, IO: 48%), or side effects (chemotherapy: 26%, IO: 19%). No significant difference was observed between median rwPFS of chemotherapy versus IO-containing therapy (7.0 months vs 5.8 months, respectively; p = 0.9419) or OS (13.0 months vs 12.6 months, respectively; p = 0.5769). Notably, patients in our cohort who received IO alone had a numerically longer rwPFS compared to chemoIO (12.6 months vs 5.8 months, respectively; p = 0.3951), as well as a numerically longer OS (12.6 months vs 6.4 months, respectively; p = 0.8885). Conclusions: This study found that there were no statistically significant differences in median rwPFS or OS between chemotherapy or IO-based regimens following the conclusion of durvalumab consolidation. Interestingly, we observed a numerically improved rwPFS and OS in those who received IO alone compared to chemoIO, which suggests there may be key clinical or molecular features that may help identify patients who benefit from IO therapy. We acknowledge the limitations of this small, retrospective study. The efficacy of IO-based regimens post-durvalumab warrants further investigation in a larger, prospective manner to assess the risks and benefits of IO retreatment.

Abstract 927: Real-world (RW) biomarker characteristics and clinical outcomes in pre-treated non-MSI-H/dMMR metastatic colorectal cancer (mCRC) patients

Abstract Introduction: Given sparse RW evidence, we assessed biomarker characteristics & clinical outcomes in community oncology practices among pre-treated non-MSI-H/dMMR mCRC patients. Methods: This retrospective cohort study used structured & chart review data from iKnowMed, The US Oncology Network electronic health record data & included non-MSI-H/dMMR adult mCRC patients pre-treated with standard of care (SoC) chemo who initiated subsequent systemic anticancer treatment (SACT), best supportive care (BSC) or neither from 1/1/2016 - 12/31/2021. Index date for SACT users was the regimen start date post SoC chemo & for patients on BSC & no SACT/BSC, it was last chemo administration date. Patients were followed from index date until 8/31/2022 for overall survival (OS) & real-world progression-free survival (rwPFS). KM analyses assessed outcomes, overall & stratified by treatment, RAS status & metastasis sites. Results: Of mCRC patients with >2 visits, 70.9% received MSI/MMR testing. In 292 eligible chart review patients, 69.5% received SACT in pre-treated setting (regorafenib 14.8%, trifluridine/tipiracil (TAS-102) 12.3%, other 72.9%), 28.8% received BSC & 1.7% neither. 76.7% reported KRAS/NRAS testing with 60.7% wild-type & 39.3% mutant. Common metastasis sites were liver-only (44.2%), liver & lung (10.3%) & lung-only (8.9%). Median (range) duration of follow-up was 5.2 (2.7, 10.0) months for regorafenib, 5.3 (2.5, 8.6) for TAS-102 & 10.7 (5.3, 18.0) for the other treatments group. Median OS was 7.4 (95% CI: 5.8, 8.8) months & median rwPFS was 3.5 (95% CI: 3.2, 4.3) months (outcomes data in Table). Conclusions: 29.1% pre-treated, mCRC patients did not receive guideline recommended MSI/MMR testing, highlighting the need to improve testing. Outcomes varied by treatment, RAS status, & metastatic sites. The modest RW clinical benefit for SoC regorafenib & TAS-102, was consistent with trials & other RW studies; all highlighting an unmet need. Cohorts Median (95% CI) OS (months) Median (95% CI) rwPFS1 (months) Overall 7.4 (5.8, 8.8) 3.5 (3.2, 4.3) Regorafenib 5.6 (3.1, 9.7) 2.4 (1.8, 3.0) TAS-102 5.9 (3.4, 8.6) 3.0 (2.1, 3.4) Other SACT2 12.8 (9.8, 17.2) 4.9 (3.7, 5.8) BSC 2.4 (1.8, 3.2) - RAS mutation Wild-type 8.6 (6.6, 11.5) 4.0 (3.3, 4.9) Mutant 5.4 (3.4, 9.5) 3.2 (2.1, 4.6) Metastatic sites Liver only 8.0 (5.7, 11.7) 3.9 (3.0, 4.9) Lung only 17.0 (7.8, 35.6) 7.9 (3.3, 10.5) Liver & lung only 5.4 (2.4, 7.2) 3.5 (2.1, 5.4) Other 6.7 (4.1, 9.4) 3.2 (2.7, 3.9) Abbreviation: CI: confidence interval, TAS-102: trifluridine/tipiracil, OS: overall survival, rwPFS: real-world progression-free survival, SACT: systemic anticancer treatment 1Overall rwPFS was calculated among patients receiving subsequent SACT only (n = 203) 2Top 2 “other SACT” included irinotecan- or oxaliplatin-based treatment Citation Format: Mayur M. Amonkar, Sneha Sura, Kaushal Desai, Rishi Jain, Zhimei Liu, Nicole Niehoff, Thomas W. Wilson, Gregory Patton, David Cosgrove. Real-world (RW) biomarker characteristics and clinical outcomes in pre-treated non-MSI-H/dMMR metastatic colorectal cancer (mCRC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 927.

Efficacy and safety of mTOR inhibition in cutaneous sarcoidosis: a single-centre trial

Sarcoidosis is an inflammatory condition that can affect various organs and tissues, causing the formation of granulomas and subsequent functional impairment. The origin of sarcoidosis remains unknown and there are few treatment options. Mechanistic target of rapamycin (mTOR) activation is commonly seen in granulomas of patients across different tissues and has been shown to induce sarcoidosis-like granulomas in a mouse model. This study aimed to examine the efficacy and safety of the mTOR inhibitor sirolimus as a treatment for cutaneous sarcoidosis. We did a single-centre, randomised study treating patients with persistent and glucocorticoid-refractory cutaneous sarcoidosis with sirolimus at the Vienna General Hospital, Medical University of Vienna (Vienna, Austria). We recruited participants who had persistent, active, and histologically proven cutaneous sarcoidosis. We used an n-of-1 crossover design in a placebo-controlled, double-blind topical treatment period and a subsequent single-arm systemic treatment phase for 4 months in the same participants. Participants initially received either 0·1% topical sirolimus in Vaseline or placebo (Vaseline alone), twice daily. After a washout period, all participants were subsequently administered a 6 mg loading dose followed by 2 mg sirolimus solution orally once daily, aiming to achieve serum concentrations of 6 ng/mL. The primary endpoint was change in the Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) after topical or systemic treatment. All participants were included in the safety analyses, and patients having completed the respective treatment period (topical treatment or systemic treatment) were included in the primary analyses. Adverse events were assessed at each study visit by clinicians and were categorised according to their correlation with the study drug, severity, seriousness, and expectedness. This study is registered with EudraCT (2017-004930-27) and is now closed. 16 participants with persistent cutaneous sarcoidosis were enrolled in the study between Sept 3, 2019, and June 15, 2021. Six (37%) of 16 participants were men, ten (63%) were women, and 15 (94%) were White. The median age of participants was 54 years (IQR 48-58). 14 participants were randomly assigned in the topical phase and 2 entered the systemic treatment phase directly. Daily topical treatment did not improve cutaneous lesions (effect estimate -1·213 [95% CI -2·505 to 0·079], p=0·066). Systemic treatment targeting trough serum concentrations of 6 ng/mL resulted in clinical and histological improvement of skin lesions in seven (70%) of ten participants (median -7·0 [95% CI -16·5 to -3·0], p=0·018). Various morphologies of cutaneous sarcoidosis, including papular, nodular, plaque, scar, and tattoo-associated sarcoidosis, responded to systemic sirolimus therapy with a long-lasting effect for more than 1 year after treatment had been stopped. There were no serious adverse events and no deaths. Short-term treatment with systemic sirolimus might be an effective and safe treatment option for patients with persistent glucocorticoid-refractory sarcoidosis with a long-lasting disease-modulating effect. The effect of sirolimus in granulomatous inflammation should be investigated further in large, multi-centre, randomised clinical trials. Vienna Science and Technology Fund, Austrian Science Fund.

Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study

Nivolumab was the first immune checkpoint inhibitor approved for hepatocellular carcinoma (HCC). External beam radiation therapy (EBRT) is locally effective and may enhance the effectiveness of immunotherapy. This study investigated the efficacy and safety of concurrent nivolumab and EBRT in HCC with macrovascular invasion. In this phase II multicenter trial, patients with HCC and macrovascular invasion were concurrently treated with intravenous nivolumab (3mg/kg every 2 weeks) and EBRT, followed by maintenance nivolumab until progression or unacceptable toxicity. Primary endpoints were progression-free survival (PFS) and safety, and secondary endpoints were overall survival, time-to-progression, objective response rate, and disease control rate. Between January 2020 and June 2021, 50 patients (male 84%, median age 62.5) were enrolled; 47 (94.0%) and 13 (26.0%) with portal (Vp1/2, n= 21; Vp3, n= 23; Vp4, n= 3) and hepatic vein invasion, respectively. Patients received EBRT (median dose: 50 [IQR 43-50] Gy) after the first nivolumab dose. The median number of nivolumab doses was 8.5. Median PFS was 5.6 (90% CI 3.6-9.9) months. Median overall survival and time-to-progression were 15.2 (90% CI 10.8-19.6) and 5.6 (90% CI 3.6-9.9) months, respectively. The objective response rate and disease control rate were 36.0% and 74.0%, respectively. The median duration of response was 9.9 months. Of 35 patients with follow-up data, 23 received subsequent systemic treatment, including atezolizumab-bevacizumab, sorafenib, lenvatinib, and regorafenib. Treatment-related any grade adverse events (AEs) and grade 3/4 AEs occurred in 40 (80.0%) and 6 (12.0%) patients, respectively. Common treatment-related AEs included pruritus (38.0%) and rash (16.0%), with no treatment-related deaths. Concurrent nivolumab therapy and EBRT showed encouraging PFS with acceptable safety in patients with advanced HCC and macrovascular invasion. Immune checkpoint inhibitors, the standard care for advanced hepatocellular carcinoma (HCC), show relatively poor therapeutic effects in patients with advanced HCC and macrovascular invasion. In this investigator-initiated phase II study, we, for the first time, show that concurrent external beam radiation therapy with nivolumab, an immune checkpoint inhibitor, led to encouraging progression-free survival in patients with HCC and macrovascular invasion. The concurrent treatment was tolerable without significant safety concerns. Further randomized studies investigating the combination of immunotherapy and external beam radiation therapy are required. NCT04611165.

Ultrasound Radiomics Features to Identify Patients With Triple-Negative Breast Cancer: A Retrospective, Single-Center Study.

Patients with triple-negative breast cancer (TNBC) exhibit a fast tumor growth rate and poor survival outcomes. In this study, we aimed to develop and compare intelligent algorithms using ultrasound radiomics features in addition to clinical variables to identify patients with TNBC prior to histopathologic diagnosis. We used single-center, retrospective data of patients who underwent ultrasound before histopathologic verification and subsequent neoadjuvant systemic treatment (NAST). We developed a logistic regression with an elastic net penalty algorithm using pretreatment ultrasound radiomics features in addition to patient and tumor variables to identify patients with TNBC. Findings were compared to the histopathologic evaluation of the biopsy specimen. The main outcome measure was the area under the curve (AUC). We included 1161 patients, 813 in the development set and 348 in the validation set. Median age was 50.1 years and 24.4% (283 of 1161) had TNBC. The integrative model using radiomics and clinical information showed significantly better performance in identifying TNBC compared to the radiomics model (AUC: 0.71, 95% confidence interval [CI]: 0.65-0.76 versus 0.64, 95% CI: 0.57-0.71, P = .004). The five most important variables were cN status, shape surface volume ratio (SA:V), gray level co-occurrence matrix (GLCM) correlation, gray level dependence matrix (GLDM) dependence nonuniformity normalized, and age. Patients with TNBC were more often categorized as BI-RADS 4 than BI-RADS 5 compared to non-TNBC patients (P = .002). A machine learning algorithm showed promising potential to identify patients with TNBC using ultrasound radiomics features and clinical information prior to histopathologic evaluation.

Adjuvant treatment and outcome of stage III melanoma patients: Results of a multicenter real-world German Dermatologic Cooperative Oncology Group (DeCOG) study

PurposeClinical trials demonstrated significantly improved recurrence-free survival (RFS) of melanoma patients receiving adjuvant treatment. As data from controlled trials are based on selected populations, we investigated adjuvantly treated stage III melanoma patients under real-world conditions. Patients and methodsIn a prior multicenter cohort study, stage III-IV melanoma patients were analysed for their choice of adjuvant therapy. In this follow-up study, we examined RFS, overall and melanoma-specific survival (MSS) and response to the subsequent treatment of 589 stage III patients (232 BRAF-mutated) receiving adjuvant PD-1 inhibitors (PD1; n = 479) or targeted therapy (TT; n = 110). ResultsThe median follow-up of the total cohort was 25.7 months. The main reason for premature discontinuation of adjuvant therapy was disease progression in PD1- (28.8%, n = 138/479) and adverse events in TT-treated patients (28.2%, n = 31/110).Among BRAF-mutated patients, RFS at 24 months was 49% (95% CI 40.6–59.0%) for PD1- and 67% (95% CI 58–77%) for TT-treated patients. The risk of recurrence was higher for BRAF-mutated PD1 than TT (hazard ratio 1.99; 95% CI 1.34–2.96; hazard ratio adjusted for age, sex and tumour stage, 2.21; 95% CI 1.48–3.30). Twenty-four months MSS was 87% (95% CI 81.0–94.1) for PD1 and 92% (95% CI 86.6–97.0) for TT.Response to subsequent systemic treatment for unresectable disease was 22% for all PD1- and 16% for TT-treated patients. ConclusionsPD1-treated patients had more and earlier recurrences than TT patients. In BRAF-mutated patients, adjuvant TT might prevent early recurrences more effectively than PD1 treatment. Management of recurrence despite adjuvant treatment is challenging, with low response to current therapeutic options.

Final survival analysis of the phase III OVHIPEC-1 trial of hyperthermic intraperitoneal chemotherapy in ovarian cancer after ten year follow-up.

5509 Background: The randomized, phase 3 OVHIPEC-1 trial (NCT00426257) investigated the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. OVHIPEC-1 previously demonstrated improved recurrence-free and overall survival after 4.7 years of follow-up. Here, we report the final survival outcomes after ten years of follow-up. In addition, we report new data on the subsequent anti-cancer treatments given after disease progression. Methods: Patients were randomized to receive interval cytoreductive surgery with or without HIPEC, after receiving three cycles of neo-adjuvant carboplatin and paclitaxel. Randomization was performed at the time of surgery when either complete (no visible disease) or optimal cytoreduction (residual tumor measuring <10mm in diameter) was anticipated. All patients received an additional three cycles of adjuvant systemic chemotherapy. We analyzed survival according to the intention-to-treat principle using stratified log-rank tests and Kaplan-Meier methods. Subsequent lines of therapy were compared between arms. Results: At a median follow-up of 10.1 years, 114 of 123 patients (92.7%) who underwent surgery alone and 109 of 122 patients (89.3%) who had surgery-plus-HIPEC experienced recurrence, progression, or death from any cause. Median recurrence-free survival was 10.7 months in the surgery group compared to 14.3 months in the surgery-plus-HIPEC group (HR, 0.63; 95% confidence interval [CI], 0.48-0.83; stratified P<0.001). One hundred and eight patients (87.8%) in the surgery group have died as compared to 100 patients (82.0%) in the surgery-plus-HIPEC group. Median overall survival was 33.3 versus 44.9 months (HR, 0.70; 95% CI, 0.53-0.92; stratified P=0.011), respectively. Subsequent anti-cancer therapies, including chemotherapy (platinum and non-platinum based), secondary surgery, poly (ADP-ribose) polymerase (PARP) inhibitors and bevacizumab, were received by 104 patients (84.6%) in the surgery group and 100 patients (82.0%) in the surgery-plus-HIPEC group. The median number of subsequent systemic treatment lines was 2 (IQR 1-3) in both arms. Conclusions: This study provides the first long-term survival analysis of HIPEC in ovarian cancer and confirms the benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. No imbalance in subsequent therapy after disease recurrence was found that could explain the improved overall survival after HIPEC. Clinical trial information: NCT00426257 .

MP28-05 THE IMPACT OF METASTASECTOMY ON SURVIVAL OUTCOMES OF RENAL CELL CARCINOMA: A 10-YEAR SINGLE CENTER EXPERIENCE

You have accessJournal of UrologyCME1 Apr 2023MP28-05 THE IMPACT OF METASTASECTOMY ON SURVIVAL OUTCOMES OF RENAL CELL CARCINOMA: A 10-YEAR SINGLE CENTER EXPERIENCE Mariaconsiglia Ferriero, Manuela Costantini, Riccardo Mastroianni, Gabriele Tuderti, Umberto Anceschi, Aldo Brassetti, Alfredo Maria Bove, Leonardo Misuraca, Andrea Iannuzzi, Salvatore Guaglianone, Michele Gallucci, and Giuseppe Simone Mariaconsiglia FerrieroMariaconsiglia Ferriero More articles by this author , Manuela CostantiniManuela Costantini More articles by this author , Riccardo MastroianniRiccardo Mastroianni More articles by this author , Gabriele TudertiGabriele Tuderti More articles by this author , Umberto AnceschiUmberto Anceschi More articles by this author , Aldo BrassettiAldo Brassetti More articles by this author , Alfredo Maria BoveAlfredo Maria Bove More articles by this author , Leonardo MisuracaLeonardo Misuraca More articles by this author , Andrea IannuzziAndrea Iannuzzi More articles by this author , Salvatore GuaglianoneSalvatore Guaglianone More articles by this author , Michele GallucciMichele Gallucci More articles by this author , and Giuseppe SimoneGiuseppe Simone More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003256.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Solitary or oligometastasis from renal cell carcinoma (RCC) are considered the ideal candidate for target treatments to delay the time to systemic therapies. The role of surgical metastasectomy and its impact on survival outcomes remains poorly addressed. We evaluated the impact of mestastasectomy on overall survival in patients with oligometastatic (m) RCC. METHODS: Institutional renal cancer prospective database was queried for cases treated with partial or radical nephrectomy who developed metastatic disease during follow up. Patients with evidence of clinical metastasis at first diagnosis were excluded. Patients were unfit for metastasectomy based on surgeon's discretion (not achievable a non evident disease [NED] status after surgery), all other patients received systemic treatment. Survival probabilities were computed at 12, 24, 60 and 120 months after primary treatments. The impact of metastasectomy vs systemic treatment only cohort (reference category) was assessed with the Kaplan Meier method. Age, gender, bilaterality, histology, AJCC stage of primary tumor, surgical margins and metastasectomy were included in univariable and multivariable regression analyses to assess predictors of overall survival (OS). RESULTS: Overall, at a median follow up of 16 months after primary treatment, 168 patients with RCC developed asynchronous metastasis at adrenal gland, lung, liver, spleen, peritoneal, renal fossa, bone, nodes, brain and thyroid gland. Nine patients unfit for any treatment were excluded. The site of metastasis was treated with surgical metastasectomy (77/159, 48.4%), with or without previous or subsequent systemic treatment (Table 1), while 82/159 cases (51.2%) received only systemic treatment. Two-yr, 5-yr and 10-yr overall survival probabilities were 82.9%,72%, 62.7% respectively. At multivariable analysis, primary tumor AJCC stage and metastasectomy were independent predictors of OS probabilities (p=0.009 and <0.001, respectively). At Kaplan Meier analysis, metastasectomy improved significantly OS probabilities versus patients receiving systemic therapy (p<0.001). (Figure 1) CONCLUSIONS: When a NED status is achievable, surgical metastasectomy of mRCC significantly impact on OS delaying and not precluding further subsequent systemic treatments. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e370 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mariaconsiglia Ferriero More articles by this author Manuela Costantini More articles by this author Riccardo Mastroianni More articles by this author Gabriele Tuderti More articles by this author Umberto Anceschi More articles by this author Aldo Brassetti More articles by this author Alfredo Maria Bove More articles by this author Leonardo Misuraca More articles by this author Andrea Iannuzzi More articles by this author Salvatore Guaglianone More articles by this author Michele Gallucci More articles by this author Giuseppe Simone More articles by this author Expand All Advertisement PDF downloadLoading ...

Effect of Prior Local Therapy on Response to First-line Androgen Receptor Axis Targeted Therapy in Metastatic Castrate-resistant Prostate Cancer: A Secondary Analysis of the COU-AA-302 Trial

BackgroundMen with localized prostate cancer are often treated with local therapy (LT). However, a proportion of these patients will eventually develop recurrence and progression requiring systemic therapy. Whether primary LT affects the response to this subsequent systemic treatment is unclear. ObjectiveWe investigated whether the receipt of prior prostate-directed LT influenced the response to first-line systemic therapy and survival in docetaxel-naïve metastatic castrate-resistant prostate cancer (mCRPC) patients. Design, setting, and participantsThis is an exploratory analysis of the COU-AA-302 trial, a multicentric double-blinded phase 3 randomized controlled trial in which mCRPC patients with no to mild symptoms were randomized to receive abiraterone plus prednisone or placebo plus prednisone. Outcome measurements and statistical analysisWe compared the time-varying effects of first-line abiraterone in patients with and without prior LT using a Cox proportional hazard model. The cut points were chosen using grid search, and were 6 and 36 mo for radiographic progression-free survival (rPFS) and overall survival (OS), respectively. We also investigated whether there was any difference in treatment effect on score change (relative to baseline) in various patient-reported outcomes (measured by Functional Assessment of Cancer Therapy—Prostate [FACT-P]) over time depending on the receipt of prior LT. The adjusted association of prior LT with survival was determined using weighted Cox regression models. Results and limitationsAmong 1053 eligible patients, 64% (n = 669) received prior LT. We did not find any statistically significant heterogeneity of time-dependent treatment effect from abiraterone on rPFS in patients with (hazard ratio [HR]: 0.36 [95% confidence interval: 0.27–0.49] at ≤6 mo; 0.64 [0.49–0.83] at >6 mo) or without (HR: 0.37 [0.26–0.55] at ≤6 mo; 0.72 [0.50–1.03] at >6 mo) prior LT. Similarly, there was no significant heterogeneity in time-dependent treatment effect on OS with (HR: 0.88 [0.71–1.10] at ≤36 mo; 0.76 [0.52–1.11] at >36 mo) or without (0.78 [0.60–1.01] at ≤36 mo; 0.55 [0.30–0.99] at >36 mo) prior LT. We did not find sufficient evidence of a difference in treatment effect from abiraterone on score change over time in prostate cancer subscale (interaction p = 0.4), trial outcome index (interaction p = 0.8), and FACT-P total score (interaction p = 0.6) depending on the receipt of prior LT. Receipt of prior LT was associated with a significant improvement in OS (average HR: 0.72 [0.59–0.89]). ConclusionsThis study demonstrates that the efficacy of first-line abiraterone and prednisone in docetaxel-naïve mCRPC do not vary significantly based on the receipt of prior prostate-directed LT. Further studies are needed to explore the plausible mechanisms of the association of prior LT with superior OS. Patient summaryThis secondary analysis of the COU-AA-302 trial suggests that survival benefits and temporal changes in quality of life with first-line abiraterone in docetaxel-naïve mCRPC do not differ significantly among patients who received versus those who did not receive prior prostate-directed local therapy.

Budget Impact Analysis of Comprehensive Genomic Profiling in Advanced Non–Small Cell Lung Cancer in Taiwan

ObjectivesThe concept of precision oncology using genetic testing has become popular for cancer treatment in recent years. This research aimed to evaluate the financial impact of comprehensive genomic profiling (CGP) in patients with advanced non–small cell lung cancer before receiving any systemic treatments, compared with current practice using single-gene testing, in the hope that the findings can inform the National Health Insurance Administration the decision regarding CGP reimbursement. MethodsA budget impact analysis model was developed comparing the sum of gene testing costs, the first-line and subsequent systemic treatment costs, and other medical costs between the current practice of traditional molecular testing and the new test strategy of CGP. The evaluation time horizon is 5 years from the perspective of the National Health Insurance Administration. Outcome endpoints were incremental budget impact and life-year gained. ResultsThis research indicated CGP reimbursement would benefit 1072 to 1318 more patients receiving target therapies than the current practice and consequently had incremental 232 to 1844 life-years gained from 2022 to 2026. The new test strategy also led to higher gene testing cost and systemic treatment cost. Nevertheless, less medical resource utilization and better patient outcome were demonstrated. The incremental budget impact ranged from US dollar 19 to US dollar 27 million in the 5-year period. ConclusionThis research shows that CGP could pave the way for personalized healthcare with moderate increase of National Health Insurance budget.

Clinical factors associated with early disease progression after radioembolization for hepatocellular carcinoma and feasibility of post‐progression systemic therapy

Background and Aims Radioembolization (RE) for unresectable hepatocellular carcinoma (HCC) can provide clinical benefit for well-selected patients, whilst in others, rapid disease progression is observed. As an alternative for this patient population, new potent systemic treatment options are emerging. We aimed to identify the clinical factors associated with rapid progression following RE and assess the feasibility of starting a systemic treatment after progression. Methods A retrospective cohort study of patients with unresectable HCC undergoing RE at a single referral centre between January 2009 and December 2018. Progression-free and overall survival times were calculated. Uni- and multivariate cox regression analysis was used to assess factors associated with poor outcomes. Charts were reviewed for post-progression treatment strategies. Results Overall, 116 patients with unresectable HCC were included. Median PFS after RE was 6.7 months (95% CI 3.97–9.37), which varied significantly (P < .001) with Eastern Cooperative Oncology Group Performance Status (EGOC PS) (ECOG 0, 20.9 months [95% CI 8.6–33.2]; ECOG 1, 7.7 months [95% CI 3.1–12.1]; ECOG 2, 4.4 months [95% CI 1.7–7]). This association remained significant after multivariate testing, together with the number of HCC lesions (P = .017) and α-FP (P = .050). Progressive disease after RE occurred in 82 patients, of whom only 40 received subsequent systemic treatment. Again, ECOG PS at the time of progression was significantly better for patients who did receive systemic treatment versus those who did not (P = .002). Conclusion Patients with unresectable HCC, impaired general condition and multinodular disease have inferior outcomes after radioembolization. After RE, close monitoring of patient performance status, liver function and cancer control is warranted to allow timely initiation of systemic treatment when indicated.

Multicenter real-world data of adjuvant treatment and disease outcome of patients with melanoma with high-risk of recurrence.

9570 Background: Clinical trials demonstrated a significantly improved recurrence-free survival (RFS) of melanoma patients treated adjuvantly with immune checkpoint inhibition (ICI) and targeted therapy (TT). As data from controlled trials are based on selected populations, we investigated melanoma patients with high risk of recurrence who opted for ICI, TT, or no adjuvant treatment (NoTx) under real-world conditions. Methods: In a prior analysis of this multicenter, retrospective cohort study, patients with resected melanoma stage III-IV between 06/2018 and 09/2019 were analyzed for adjuvant therapy choice (Lodde et al., Cancers 2021). In this follow-up study, the treatment course of ICI- and TT-treated patients as well as recurrence characteristics, subsequent management and outcomes also including NoTx patients were examined. Results: 814 patients were included (72 stage IIIA, 266 IIIB, 383 IIIC, 24 IIID, 69 IV; 309 BRAF mut); 533 patients received ICI (66%), 114 TT (14%, 36.9% of all BRAF mutated patients), 167 patients had opted for NoTx (21%). Median treatment duration was 10.2 and 11.7 months for ICI and TT, respectively. ICI was discontinued prematurely in 51% (273/533) and TT in 44% (50/114) of patients. The main reason for discontinuation was progressive disease (PD) in ICI patients (58%, 158/273) and adverse events in TT patients (60%, 33/50). At a median follow-up (FU) of 24.6 months for ICI, 25.3 months for TT, and 21.8 months for NoTx, 48% of ICI (255/533), 35% of TT (40/114), and 45% of NoTx (75/167) patients had developed a recurrence mostly at distant sites (ICI 62%, TT 63%, NoTx 64%). In patients with recurrence, median time from start of adjuvant treatment to 1st recurrence was 6.1 months in ICI and 17.6 months in TT. Median RFS was 32.0 months for ICI (95% CI 25.7-38.3), not reached for TT, and 22.3 months for NoTx (95% CI 15.2-29.4). Among BRAF mut patients with stage III, risk of recurrence was higher for ICI than TT (hazard ratio adjusted for age, sex and tumor stage, 2.31; 95% CI 1.56-3.43). Subsequent systemic treatment for the 1st recurrence was given in 76% (192/253) of ICI, 83% (33/40) of TT, and 53% (40/75) of NoTx patients. Among patients who received the 1st subsequent systemic treatment for metastatic disease, PD was the best response in 67% (82/123) for ICI, 55% (11/20) for TT, and 50% (16/32) for NoTX. Conclusions: After 2 years of FU, recurrences were mostly at distant sites in all groups. ICI had higher discontinuation rates and more and earlier recurrences than TT. BRAF mut melanoma patients treated with ICI had a significantly higher risk of relapse than TT-treated patients. Response to subsequent systemic treatment was low for both ICI and TT.

Stereotactic body radiotherapy (SBRT) and concomitant systemic therapy in oligoprogressive breast cancer patients

Breast cancer is a heterogenous disease with a deep tailoring level. Evidence is accumulating on the role of stereotactic body radiotherapy (SBRT) in the management of oligometastatic disease, however this is limited in breast cancer. The aim of the present study is to show the effectiveness of SBRT in delaying the switch to a subsequent systemic treatment in oligoprogressive breast cancer patients. Retrospective analysis from two Institutions. Primary endpoint: time to next systemic treatment (NEST). Secondary endpoints: freedom from local progression (FLP), time to the polymetastatic conversion (tPMC) and overall survival (OS). One-hundred fifty-three (153) metastases in 79 oligoprogressive breast cancer patients were treated with SBRT. Median follow-up 24months. Median NEST 8months. Predictive factor of NEST at the multivariate analysis (MVA) was the number of treated oligometastases (HR 1.765, 95%CI 1.322-2.355; p = < 0.01). Systemic treatment after SBRT was changed in 29 patients for polymetastatic progression and in 10 patients for oligometastatic progression < 6months after SBRT. The 2-year FLP in the overall population was 86.7%. A biological effective dose (BED) > 70Gy10 was associated with improved FLP (90% versus 74.2%). The median tPMC was 10months. At the MVA the only factors significantly associated with tPMC were the number of oligometastases (HR 1.172, 95%CI 1.000-1.368; p = 0.03), and the local control of the treated metastases (HR 2.726, CI95% 1.108-6.706; p = 0.02). SBRT can delay the switch to a subsequent systemic treatment, however patient selection is necessary. Several predictive factors for treatment tailoring have been identified.

Clinical practice pattern in patients with advanced urothelial cancer who had progressed on pembrolizumab in the pre‐enfortumab vedotin era

Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment for advanced urothelial carcinoma. However, the standard treatment for patients after disease progression with pembrolizumab had not been established until the recent approval of enfortumab vedotin. We analyzed the treatment of these patients in the real world, and the patient background and outcomes. We extracted data from 543 patients who experienced progressive disease after pembrolizumab initiation from a Japanese nation-wide cohort of platinum-refractory, metastatic urothelial carcinoma. The median overall survival of the 543 patients was 3.5 months (95% confidence interval 3.0-4.1). Of these, only 20.6% (n = 112) received chemotherapy as a subsequent systemic treatment after progressive disease. The regimen of chemotherapy was very diverse. The median overall survival was 11.9 months (95% confidence interval 9.2-14.7) for patients who received chemotherapy, compared to 2.4 months for those who did not receive chemotherapy (95% confidence interval 2.1-2.9; P < 0.0001). Patients who received subsequent chemotherapy were more likely to have better performance status, neutrophil-to-lymphocyte ratio <3, hemoglobin >11 mg/dL, and history of a single chemotherapeutic regimen at pembrolizumab initiation. This report highlights the real-world practice of the management after pembrolizumab treatment failure in the pre-enfortumab vedotin era, characterized by infrequent use of subsequent anticancer therapy comprising various regimens, reflecting the lack of a standard treatment. Clinical introduction of enfortumab vedotin is expected to improve treatment outcomes in this setting. The present study will provide important baseline data for evaluating the influence of enfortumab vedotin on clinical practices and outcomes.

Application and Development of Minimally Invasive Techniques in the Treatment of Spinal Metastases.

With the improvement of medical technology, the quality of life and prognosis of patients with malignant tumors have been greatly improved, and surgical treatment strategies for patients with spinal metastatic tumors have received extensive attention. Traditional open surgery for spinal metastases has problems such as large trauma, slow recovery, and influence on subsequent systemic treatment. Minimally invasive spine surgery has similar clinical outcomes to traditional open surgery, but minimally invasive spine surgery is less invasive and has a shorter recovery time. Minimally invasive spine surgery was initially applied to non-neoplastic diseases such as spinal degeneration and trauma, and was gradually applied to the treatment of spinal metastatic tumors and spinal deformities. For patients with spinal metastases, a shorter recovery time is helpful for early postoperative radiotherapy, thereby achieving a more satisfactory tumor control effect. This review discusses the application of minimally invasive spine surgery in the treatment of spinal metastatic tumors from the concept, surgical purpose, indications, and surgical selection, so as to provide reference for clinical practice.

Efficacy and Safety of Local Radiotherapy to All Oligometastatic Sites in Elderly Patients with Metachronous Oligometastatic Cancers After Initial Treatment for the Primary Tumor.

Background and PurposeThis study aimed to investigate the efficacy and safety of maintenance therapy combined with local radiotherapy at all oligometastatic sites (LRTOS) in elderly patients with metachronous oligometastatic cancers (MOC).Patients and MethodsA total of 242 elderly patients with MOC (≤5 metastases) and primary tumor well controlled after definitive treatment was retrospectively analyzed between August 2014 and February 2020 at Beijing Geriatric Hospital and Air Force General Hospital. Patients were divided into maintenance therapy group (maintenance therapy alone) and local radiotherapy group (maintenance therapy combined with LRTOS).ResultsThere were 86 patients in the local radiotherapy group and 156 patients in the maintenance therapy group. The median length of follow-up was 36 months (range, 8.0–62 months). Median overall survival (mOS) was 25 months (95% CI: 21.1–28.9) in the local radiotherapy group and 16 months (95% CI: 14.5–17.6) in the maintenance therapy group (p < 0.001). Multivariate analyses demonstrated that LRTOS (hazard ratio (HR) = 0.49, 95% confidence interval (CI): 0.35–0.67, p < 0.001), good Eastern Cooperative Oncology Group Performance Status (ECOG PS, HR = 0.69, 95% CI: 0.49–0.97, p = 0.032), longer duration between diagnosis of primary tumor and occurrence of progression (HR = 0.87, 95% CI: 0.78–0.97, p = 0.015), and subsequent systemic treatment (HR = 0.52, 95% CI: 0.38–0.72, p < 0.001) were independent predictors of good OS. In patients who did not receive subsequent systemic treatment, their mOS was 21 months (95% CI: 12.8–29.2) for those treated with LRTOS and 14 months (95% CI: 11.4–16.6) for those who did not receive local radiotherapy (p = 0.001). Further multivariate analysis showed that LRTOS was the only independent factor for predicting good OS (HR = 0.47, 95% CI: 0.26–0.83, p = 0.010). Patients with metachronous oligometastatic lung cancer, colorectal cancer, prostate cancer, and breast cancer had higher survival benefits following LRTOS. Most patients suffered from grade 1–2 toxicities, but no treatment-related death was recorded.ConclusionThis retrospective study shows that elderly patients with MOC treated with LRTOS may have better survival outcomes.

Outcomes of Patients with Diffuse Large B Cell and High-Grade B Cell Lymphomas with Synchronous CNS and Systemic Involvement at Diagnosis Treated with High-Dose Methotrexate and R-CHOP: A Single-Center Retrospective Study

Outcomes of Patients with Diffuse Large B Cell and High-Grade B Cell Lymphomas with Synchronous CNS and Systemic Involvement at Diagnosis Treated with High-Dose Methotrexate and R-CHOP: A Single-Center Retrospective Study

Surgery due to mechanical bowel obstruction in relapsed ovarian cancer: clinical and surgical results of a bicentric analysis of 87 patients

IntroductionMechanical bowel obstruction is a frequent acute and life-threatening event in relapsed ovarian cancer. Salvage surgery after failure of all conservative approaches, resulting in short bowel syndrome (SBS) constitutes a therapeutic dilemma. Our aim was to evaluate patients’ surgical and clinical outcome in these highly palliative situations. Previous, limited, data reported a high morbidity and mortality. However, recent surgical and therapeutical improvements in relapsed ovarian cancer (ROC) offer better identification of patients who might benefit from surgery in an effort to extend the window of opportunity to subsequently offer these patients novel systemic therapeutic approaches.Material and methodsAll subsequent ROC patients between 2012 and 2017 with acute mechanical bowel obstruction who underwent salvage extraperitoneal en bloc intestinal resection were retrospectively identified. Data were collected from two ESGO certified Ovarian Cancer Centers of Excellence (Charité Berlin and Imperial College London) and systematically evaluated regarding surgical and clinical outcomes.ResultsOverall, 87 ROC patients were included in the analysis (median age 56 years, range 24–88), 47% were platinum resistant. High grade serous was the most common histology (76%) while most of the patients (67%) had at least two previous lines of treatment. Mean observed OS was 7.8 months. After salvage surgery, 46% of the patients had a residual small bowel length < 180 cm and 18% > 180 cm resulting in 41% in need of total parental nutrition. In 80% of the patients a permanent stoma was necessary. 30d morbidity and mortality was 74% and 10%, respectively. More than half of the patients were able to receive further courses of chemotherapy after surgery.DiscussionSalvage surgery for bowel obstruction in ROC patients needs careful consideration and identification of optimal surgical candidates to have the maximal therapeutic benefit. Despite the challenging morbidity profile, most patients managed to proceed to subsequent novel and conventional systemic treatment and so have their window of therapeutic opportunity extended.

922P Efficacy of immunotherapy (IO) and subsequent systemic treatment after failure of IO in patients with recurrent or metastatic head and neck cancer in a real-world setting

Immune checkpoint inhibitors (CPI) are the standard of care in patients (pts) failing platinum-based therapy for recurrent or metastatic head and neck cancer (r/m SCCHN). Here we explored the overall clinical impact of CPI in two real-world patient cohorts.