Favorable Progression-free Survival Research Articles

Weekly Paclitaxel, Carboplatin, and Cetuximab as First-Line Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma for Patients Ineligible to Cisplatin-Based Chemotherapy: A Retrospective Monocentric Study in 60 Patients.

ObjectiveFor most patients suffering from recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), chemotherapy is the main option after considering surgery and reirradiation. Cetuximab combined with a platinum-fluorouracil regimen (EXTREME) has been the standard of care for over a decade. Nevertheless, a significant number of patients remain unfit for this regimen because of age, severe comorbidities, or poor performance status. The aim of this study is to investigate an alternative regimen with sufficient efficacy and safety.MethodsWe reviewed retrospectively the medical charts of all patients treated with paclitaxel, carboplatin, and cetuximab (PCC) at our institution. Eligibility criteria were as follows: first-line R/M-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx not suitable for local therapy, cisplatin, and/or 5-FU ineligibility, ECOG-PS: 0–2. PCC consisted of paclitaxel 80 mg/m2, carboplatin AUC 2, and cetuximab at an initial dose of 400 mg/m2 then 250 mg/m2, for 16 weekly administrations followed by cetuximab maintenance for patients for whom a disease control was obtained. The primary endpoint was overall survival (OS), and secondary endpoints were overall response rate (ORR), progression free survival (PFS), and safety.ResultsWe identified 60 consecutive patients treated with PCC between 2010 and 2016 at our institution. Thirty-one patients (52%) were ECOG-PS 2. Fifty-five patients (92%) were cisplatin ineligible. ORR was 43.3% (95% CI, 30.8–55.8), and disease control rate was 65% (95% CI, 52.9–77.1). With a median follow-up of 35.7 months (IQR 28.6–48.8), median PFS was 5.8 months (95% CI, 4.5–7.2), and median OS was 11.7 months (95% CI, 7.5-14.8). For ECOG-PS 0–1 patients, median OS was 14.8 months (95% CI, 12.2–21.7) while it was only 7.5 months (95%CI: 5.5-12.7) for ECOG-PS 2 patients (p < 0.04). Grades III–IV toxicities occurred in 30 patients (50%). Most toxicities were hematologic. Six patients (10%) had febrile neutropenia. Nonhematologic toxicities were reported such as cutaneous toxicities, neuropathy, infusion-related reactions, or electrolyte disorders.ConclusionThe weekly PCC regimen seems to be an interesting option in cisplatin-unfit patients. This study shows favorable PFS and OS when compared with what is achieved with the EXTREME regimen and a high controlled disease rate with predictable and manageable toxicities even in the more fragile population.

Does Disease Burden on PET Predict Outcomes for Advanced NSCLC Patients Treated With First-Line Immunotherapy?

First-line immunotherapy (IT), with or without chemotherapy (CTX), is now recommended for most patients with advanced non-small cell lung cancer (NSCLC) with no treatable driver mutations. Trials performed before first-line IT became standard suggested that patients with oligometastatic disease (OMD) may have a favorable prognosis and benefit from aggressive local therapy. We reviewed outcomes for NSCLC patients treated with first-line IT at our institution to test the hypothesis that measures of disease burden on staging FDG-PET would have prognostic value and examine if the presence of brain metastases (BM) affects prognosis.Advanced NSCLC patients who were staged with FDG-PET and treated with first-line IT between 2015 and 2019 were included in this analysis. Patient, disease, and treatment details were collected. A gradient-based segmentation tool was used to delineate each PET-avid extracranial lesion. Number of extrathoracic lesions, composite metabolic tumor volume (MTV), and presence of BM were tabulated. OMD was defined as having 3 or fewer extrathoracic lesions, with any number of thoracic lesions. Progression-free survival (PFS) and overall survival (OS) rates following initiation of IT were evaluated using the Kaplan-Meier method, and predictors of PFS and OS were assessed using Cox proportional hazards models and log rank tests.One hundred twenty-four patients met inclusion criteria, and 1,143 lesions were contoured. Seventy-four patients (60%) had OMD. Median MTV was 88 cc (interquartile range: 33 to 206 cc). Thirty-two patients (26%) had BM. Fifty-eight patients (47%) received IT with CTX. With a median follow-up duration of 17.3 months for surviving patients, the median PFS and OS durations were 8.5 and 36.5 months, respectively. The presence of OMD was associated with favorable PFS (median 13.1 vs. 6.9 months, P = 0.011) and OS (median not reached vs. 20.7 months, P = 0.003). In multivariable models adjusted for performance status, PD-L1 TPS, and receipt of CTX, OMD was associated with favorable PFS (HR = 0.62, P = 0.044) and OS (HR = 0.43, P = 0.018), and high MTV was associated with inferior OS (HR 1.12 per 100 cc, P = 0.048). Among patients who developed progressive disease, the brain was the first site of progression for 12 of 21 patients (57%) with BM at diagnosis and 2 of 55 patients (4%) without BM at diagnosis (P < 0.001). However, the presence of BM at diagnosis was not significantly associated with OS (HR = 0.84, P = 0.642) or PFS (HR = 1.13, P = 0.631) in multivariable models.For advanced NSCLC patients treated with first-line IT, having OMD is a favorable prognostic factor. Volume of disease on FDG-PET could provide additional prognostic information. The presence of brain metastases does not seem to affect outcomes, which may reflect the activity of IT in the central nervous system and should be considered when designing clinical trials.

Prognostic value of PSA bounce after definitive radiotherapy revisited.

Prostate-specific antigen (PSA) bounce after definitive radiotherapy has been reported as a predictor of improved biochemical recurrence-free survival (BCRFS). We revisited this phenomenon to confirm its clinical impact on oncological outcomes in patients with long-term follow-up who were free of biochemical recurrence (BCR) at least 3years after treatment. A total of 541 patients with localized, intermediate-risk prostate cancer underwent low-dose rate brachytherapy with iodine-125 seeds with or without supplemental external beam radiotherapy in combination. Neoadjuvant hormonal therapy was administered to 273 patients (50.5%) with a median duration of 3months (range 1-108months). PSA bounce was defined as ≥ 0.2ng/ml increase above the interval PSA nadir, followed by a decrease below that value. The median age was 69years (range 49-90years). The median follow-up duration was 102months (range 36-205months). One-hundred and fifty patients (27.7%) had PSA bounce with a median magnitude of 0.47ng/ml (range 0.2-3.19ng/ml). Age was significantly associated with the occurrence of PSA bounce [age: hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.93-0.98]. It was found to be independently associated with a decreased risk for BCR (HR 0.29; 95% CI 0.12-0.69) and clinical progression (HR 0.44; 95% CI 0.95-0.98). PSA bounce indicated a favorable BCRFS and clinical progression-free survival in patients who had been free of BCR for at least 3years after definitive radiotherapy.

Efficacy of hyperthermic intraperitoneal chemotherapy and interval debulking surgery in women with advanced uterine serous carcinoma

Objective(s)To investigate the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of iterval debulking surgery (IDS) in women with advanced uterine serous carcinoma (USC) following neoadjuvant chemotherapy (NACT). MethodsAn IRB-approved single-institution prospective registry was queried to identify women with incidentally identified USC at the time of IDS + HIPEC for high-grade serous carcinoma. Patient demographic, oncologic, and surgical outcomes data were recorded. Univariate analysis determined progression-free survival (PFS) and overall survival (OS). ResultsIn total, seven patients were found to have advanced USC after undergoing IDS + HIPEC, with a median age of 64.5 years. The majority had stage IV, (n = 6, 85.7%), MMR proficient (n = 5, 71.4%), p53 mutant (n = 6, 85.1%) USC. The median pre-operative CA125 was 24.0U/mL. HIPEC regimen was cisplatin (n = 3, 42.9%) or cisplatin with paclitaxel (n = 4, 57.1%). All patients underwent optimal cytoreduction, with 71.4% (n = 5) having no gross residual disease. Accordion post-operative complications were mild in 14.3% (n = 1), moderate in 57.1% (n = 4) and severe in 14.3% (n = 1); 14.3% (n = 1) had no complications. The median length of stay was 6.5 days (IQR 4–8 days) with a median time to chemotherapy of 33.0 days. The median PFS was 14.0 months (95% CI 3.5–20.8 months), and the median OS was 27.0 months (95% CI 5.1- not reached). ConclusionsIn this small, prospective series, we demonstrate that IDS + HIPEC is well tolerated in patients with USC and is associated with favorable PFS and OS following NACT. Further prospective investigation is needed to validate these promising findings in larger, heterogeneous cohorts of women with advanced USC who are not candidates for primary surgical management.

Identification and clinical significance of somatic oncogenic mutations in epithelial ovarian cancer

ObjectiveEpithelial ovarian cancer (EOC) is a heterogeneous disease with diverse clinicopathological features and behaviors, and its heterogeneity may be concerned with the accumulation of multiple somatic oncogenic mutations. The major goals of this study are to systematically perform the comprehensive mutational profiling in EOC patients, and investigate the associations between somatic mutations and clinicopathological characteristics.MethodsA total of 80 surgical specimens were obtained from EOC patients who had previously undergone primary debulking surgery, and genomic DNAs were extracted from fresh-frozen tissues. We investigated mutational status in hot spot regions of 50 cancer-related genes by targeted next-generation sequencing using an Ion AmpliSeq Cancer Hotspot Panel v2 Kit.ResultsValidated mutations were detected in 66 of the 80 tumors (82.5%). The five most frequently mutated genes were TP53 (43.8%), PIK3CA (27.5%), KRAS (23.8%), PTEN (10%) and CTNNB1 (10%). PTEN and CTNNB1 mutations were associated with younger age. PIK3CA1, KRAS and CTNNB1 mutations were observed in early-stage, whereas TP53 mutations were more common in advanced stage. Significant associations were observed between TP53 mutation and serous carcinoma, and between KRAS mutation and mucinous carcinoma. Both PIK3CA mutation and CTNNB1 mutation were also significantly associated with endometrioid and clear cell carcinoma. The patients with PIK3CA and KRAS mutations were significantly associated with favorable progression free survival (PFS). In particular, PIK3CA mutations had more significant associations with favorable PFS than PIK3CA wild-type in the endometrioid subtype (P = 0.012). Patients with mutations only in TP53 were significantly associated with worse PFS.ConclusionEOCs were heterogeneous at the genomic level and harbored somatic oncogenic mutations. Our molecular profiling may have the potential for becoming a novel stratification within histological subtypes of EOC. Further studies are needed to define molecular classification for improved clinical outcomes and treatment of EOC patients in future.

Prognostic factors of patients with advanced lung cancer treated with anlotinib: a retrospective cohort study.

ObjectiveOur study aimed to evaluate the main factors affecting the efficacy of anlotinib to determine the therapeutically dominant populations.MethodsThe medical records of patients with lung cancer who were treated with anlotinib from July 2018 to February 2020 at Renji Hospital, School of Medicine, Shanghai Jiaotong University were retrospectively reviewed. The optimal cutoff prognostic nutritional index (PNI) value for predicting efficacy was determined according to receiver operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were calculated and compared using the Kaplan–Meier method and log‐rank test. The prognostic values of each variable were evaluated with univariate and multivariate Cox proportional hazard regression analyses.ResultsThe overall disease control rate of 44 patients with lung cancer was 93.2% (41/44). The median PFS was 5.0 months (95% [confidence interval] CI: 2.2–7.8), and the median OS was 6.5 months (95% CI: 3.6–9.3). The multivariate analysis results indicated that hand–foot syndrome and high PNI values were independent protective factors of PFS and OS.ConclusionsAnlotinib was effective in treating locally advanced or advanced lung cancer. High pretreatment PNI scores and the presence of hand–foot syndrome after treatment were independent prognostic markers for favorable OS and PFS.

P28.03 Durvalumab Adjuvant to Chemoradiation for Patients With Locally Advanced Non-Small Cell Lung Cancer: Real World Experience

Approximately one third of patients with non-small cell lung cancer (NSCLC) are diagnosed with locally advanced disease (LA-NSCLC). The standard treatment for patients with unresectable disease has been concurrent chemoradiation. The prognosis has been poor with median progression-free survival of approximately 8 months and 15% 5-year overall survival. The PACIFIC trial evaluated the effect of one year adjuvant treatment with durvalumab for patients who did not progress after chemoradiation, and presented favourable progression-free survival for patients receiving durvalumab compared with placebo in September 2017.

Clinical Outcomes and Adverse Events after First-Line Treatment in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis.

Four recent first-line clinical trials leveraging immune-oncology agents demonstrated an overall survival (OS) benefit relative to sunitinib. We aimed to provide formal comparisons among immune-oncology combinations in terms of OS, progression-free survival (PFS), objective response rates and treatment-related adverse events (AEs). PubMed® database was searched for studies indexed from January 1, 2016 through March 6, 2021. Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included: CheckMate 214 (nivolumab plus ipilimumab [N+I]), KEYNOTE-426 (pembrolizumab plus axitinib [P+A]), CheckMate 9ER (nivolumab plus cabozantinib [N+C]) and KEYNOTE-581 (lenvatinib plus permbrolizumab [L+P]). OS represented the primary outcome. PFS, objective response rate and AEs represented secondary outcomes. Overall, 3,320 patients were included. Regarding OS, N+C ranked first, followed by L+P, P+A and N+I. Regarding PFS and objective response rate, L+P ranked first, followed by N+C, P+A and N+I. Finally, N+I ranked first with respect to lowest grade 3+ AEs, followed by P+A, N+C and L+P. Differences in followup duration, risk grouping and nephrectomy rates distinguish the studies. N+C may provide the most favorable OS, L+P the most favorable PFS and ORRs, and N+I the lowest toxicity. Population differences may potentially undermine the generalizability and the robustness of findings of metastatic renal cell carcinoma.

Carfilzomib, Lenalidomide, and Dexamethasone Followed by Salvage Autologous Stem Cell Transplant with or without Maintenance for Relapsed or Refractory Multiple Myeloma.

Simple SummaryHigh-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) is a standard treatment in patients with newly diagnosed multiple myeloma (MM). At relapse, salvage HDCT/ASCT is a treatment option in patients with sufficient benefit from frontline HDCT/ASCT, but no evidence is currently available regarding its role in the era of triplet regimens combining the most active drug classes for relapsed MM. To evaluate the outcome after salvage HDCT/ASCT following re-induction treatment with carfilzomib/lenalidomide/dexamethasone (KRD) and to identify prognostic factors, we conducted a retrospective analysis of patients that had previously undergone frontline HDCT/ASCT. We found that deep remissions achieved with KRd followed by salvage autologous transplantation were associated with favorable PFS and were enhanced by maintenance treatment. Salvage autologous transplantation after state-of-the-art triplet re-induction was a safe and effective strategy for RRMM patients that may offer the chance to avoid refractoriness to multiple novel agents at the next relapse.Salvage high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) is a treatment option for relapsed and/or refractory multiple myeloma (RRMM). No data are available on salvage HDCT/ASCT following re-induction treatment with state-of-the-art triplet regimens. We retrospectively report on 44 patients receiving salvage HDCT/ASCT following re-induction with carfilzomib/lenalidomide/dexamethasone (KRd). All patients received frontline HDCT/ASCT with median time to progression (TTP1) of 2.9 (1.2–13.5) years, enabling paired comparison of frontline and salvage HDCT/ASCT. After re-induction and before salvage transplant, 25/44 patients (57%) attained ≥ very good partial response (VGPR), which increased to 34/44 (77%) at best response after salvage HDCT/ASCT. Median progression-free survival (PFS) was 23.3 months from salvage HDCT/ASCT. Patients with ≥ VGPR at the time of salvage HDCT/ASCT and those receiving maintenance treatment post salvage HDCT/ASCT had significantly superior PFS (hazard ratio (HR) 0.19, p = 0.001 and HR 0.20, p = 0.009). In patients achieving at least an equal depth of response before salvage HDCT/ASCT as before frontline HDCT/ASCT, PFS after salvage HDCT/ASCT was comparable to the frontline situation (p = 0.3). This is the first report of state-of-the-art triplet re-induction and salvage HDCT/ASCT for RRMM after frontline transplantation. Deep remissions achieved with KRd translate into prolonged PFS following salvage HDCT/ASCT and are enhanced by maintenance treatment.

P16INK4A expression might be associated with a favorable prognosis for cervical adenocarcinoma via dysregulation of the RB pathway

Previous studies have largely failed to clarify the relationship between p16INK4A status and cervical adenocarcinoma prognosis. The current study aimed to examine the clinical and pathological significance of p16INK4A expression in several cervical adenocarcinoma subtypes. Eighty-two samples collected from patients with cervical adenocarcinoma were formalin fixed and paraffin embedded. Next, p16INK4A levels were analyzed with immunohistochemistry. Additionally, the relationship between p16INK4A expression and clinicopathological factors as well as prognosis was evaluated. The expression of p16INK4A was mostly detected in all usual cervical adenocarcinoma subtypes. In the gastric type, only a few cases were positive for p16INK4A expression. Results of the Kaplan–Meier analysis indicated that the positive p16INK4A expression in tumor cells was significantly associated with favorable progression-free survival and overall survival in patients with cervical adenocarcinoma (p = 0.018 and p = 0.047, respectively, log-rank test). Our findings suggest that the status of p16INK4A expression may influence prognosis. Thus, p16INK4A expression could be used as a biomarker for improving the prognosis of patients with cervical adenocarcinoma.

P14.14 Adjuvant treatment versus initial observation in newly diagnosed WHO grade II and grade III oligodendroglioma: real-life data from two academic, tertiary care centers in Austria

Abstract BACKGROUND Oligodendrogliomas are rare, slow-growing brain tumors with a survival prognosis of &amp;gt;10 years. Although adjuvant radio-chemotherapy has been shown to prolong survival, aggressive treatment comes at the cost of increased toxicity. Systematic data on the optimal timing of adjuvant treatment in oligodendroglioma are lacking. MATERIAL AND METHODS Patients treated for a newly diagnosed IDH-mutated, 1p/19q-codeleted oligodendroglioma (WHO grades II/III) in 2000 - 2018 at the Medical University of Vienna or the Kepler University Hospital Linz (Austria) were included in this retrospective study. Adjuvant treatment was defined as radiotherapy (RT), chemotherapy (CHT) or radio-chemotherapy (R-CHT) within 6 months after resection in the absence of progression. “Wait and see” was defined as regular follow up with magnetic resonance imaging and treatment at progression. RESULTS 185 patients were identified, comprising 123/185 (66.5%) WHO grade II and 62/185 (33.5%) WHO grade III oligodendrogliomas. Median age at diagnosis was 42 years (range: 20–82). Gross total resection (GTR) could be achieved in 77/178 (42.3%) evaluable patients. Adjuvant treatment was applied in 63/185 (38.2%) patients, of whom 43/63 (68.3%) underwent R-CHT, 9/63 (14.3%) CHT only and 11/63 (17.5%) RT only. 43/52 (82.7%) received temozolomide-based treatment, 1/52 (1.9%) procarbazine, lomustine and vincristine (PCV), 1/52 dacarbazine/fotemustine and in 7/52 (13.5%) patients, no data on used regimens was available. Adjuvant treatment was more frequently applied in WHO grade 3 tumors (p&amp;lt;0.001), while there was no association of adjuvant treatment with extent of resection (p=0.24). Patients after GTR who underwent adjuvant therapy presented with longer progression-free survival (PFS) compared to patients initially managed with observation (median: 150 months, 95%CI: 100 - not reached (n.r.) vs. median: 101 months, 95%CI: 73.2–115; p=0.053). In non-GTR tumors, patients with adjuvant therapy presented with a significantly longer median PFS of 107.5 months (95%CI: 62.8-n.r.) as compared to patients initially managed with observation (45.3 months, 95%CI: 41.2–78.8; p=0.025). CONCLUSION The application of adjuvant therapy was associated with favorable PFS in patients who underwent resection of newly diagnosed oligodendroglioma in this retrospective study. Prospective clinical trials should investigate the risks and benefits of adjuvant treatment versus initial observation in patients with oligodendroglioma.

Insertion-deletion rate is a qualitative aspect of the tumor mutation burden associated with the clinical outcomes of gastric cancer patients treated with nivolumab.

We aimed to investigate the clinical implications of the tumor mutation burden (TMB) and insertion-deletion (indel) rate in gastric cancer patients treated with nivolumab. A total of 105 patients with advanced gastric cancer who were treated with nivolumab as third or later line of therapy were included as the study population. The indel rate was defined as the proportion of indels making up the TMB. The median age was 58 (32-78years), and 65 (61.9%) were men. Patients with TMB > 18.03/Mb showed superior progression-free survival (PFS) and overall survival (OS) compared to those with TMB ≤ 18.03/Mb. Patients with a high indel rate (> 40%) had a favorable PFS and OS compared to those with a lower indel rate (≤ 40%) (P = 0.009 and P = 0.007, respectively). The association between a high indel rate and favorable PFS and OS was prominent in a subgroup with TMB > 18.03/Mb (P < 0.001 and P = 0.007 for PFS and OS, respectively), but not in that with TMB ≤ 18.03/Mb. All five patients with deficient-MMR fell into the category of 'TMB > 18.03/Mb with an indel rate of > 40%. TMB ≥ 18.03/Mb with an indel rate of > 40% was independently associated with a favorable PFS (hazard ratio [HR] 0.07, P = 0.012) and OS (HR 0.09, P = 0.023). TMB and indel rate should be jointly considered to better predict survival outcomes of gastric cancer patients treated with nivolumab. Our findings deserve further investigation and validation in future studies.

PD40-07 CLINICAL OUTCOMES AND ADVERSE EVENTS AFTER FIRST-LINE TREATMENT IN METASTATIC RENAL CELL CARCINOMA: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) II (PD40)1 Sep 2021PD40-07 CLINICAL OUTCOMES AND ADVERSE EVENTS AFTER FIRST-LINE TREATMENT IN METASTATIC RENAL CELL CARCINOMA: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS Luigi Nocera, Pierre Karakiewicz, Mike Wenzel, Shahrokh Shariat, Fred Saad, Felix Chun, Alberto Briganti, Anil Kapoor, Aly-Khan Lalani, Alberto Martini, Alessandro Larcher, Luigi Candela, Antony Pellegrino, Giuseppe Fallara, Gianfranco Baiamonte, Cristina Giancristofaro, Roberto Bertini, Andrea Necchi, Francesco Montorsi, and Umberto Capitanio Luigi NoceraLuigi Nocera More articles by this author , Pierre KarakiewiczPierre Karakiewicz More articles by this author , Mike WenzelMike Wenzel More articles by this author , Shahrokh ShariatShahrokh Shariat More articles by this author , Fred SaadFred Saad More articles by this author , Felix ChunFelix Chun More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Anil KapoorAnil Kapoor More articles by this author , Aly-Khan LalaniAly-Khan Lalani More articles by this author , Alberto MartiniAlberto Martini More articles by this author , Alessandro LarcherAlessandro Larcher More articles by this author , Luigi CandelaLuigi Candela More articles by this author , Antony PellegrinoAntony Pellegrino More articles by this author , Giuseppe FallaraGiuseppe Fallara More articles by this author , Gianfranco BaiamonteGianfranco Baiamonte More articles by this author , Cristina GiancristofaroCristina Giancristofaro More articles by this author , Roberto BertiniRoberto Bertini More articles by this author , Andrea NecchiAndrea Necchi More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Umberto CapitanioUmberto Capitanio More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002050.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Four recent first line clinical trials that leverage immune-oncology agents have demonstrated an overall survival benefit relative to sunitinib. However, formal network meta-analysis-based comparisons have not yet been presented. We present these comparisons in this analysis. We aimed to provide comparisons of overall survival (OS), progression-free survival (PFS), objective response rates (ORR) and adverse events (AEs). METHODS: Pubmed database was searched for studies indexed from 2016 through 2021, including conference abstracts. The systematic search was supplemented by hand search. Only phase III randomized clinical trials with proven OS benefit, relative to sunitinib, were included: CheckMate 214 (nivolumab plus ipilimumab), KEYNOTE-426 (pembrolizumab plus axitinib), CheckMate 9ER (nivolumab plus cabozantinib) and KEYNOTE-581 (lenvatinib plus permbrolizumab). OS represented the primary outcome of the study. PFS, ORR and AEs represented secondary outcomes. RESULTS: Overall, 3,320 patients from four trials were included. Regarding OS, nivolumab plus cabozantinib ranked first, followed by lenvatinib plus pembrolizumab, pembolizumab plus axitinib and nivolumab plus ipilimumab, in that order. Conversely, regarding PFS, lenvatinib plus pembrolizumab ranked first, followed by nivolumab plus cabozantinib, pembrolizumab plus axitinib and nivolumab plus ipilimumab. Similarly, lenvatinib plus pembrolizumab ranked first with respect to ORR, followed by nivolumab plus cabozantinib, pembrolizumab plus axitinib and nivolumab plus ipilimumab, in that order. Finally, nivolumab plus ipilimumab ranked first with respect to lowest grade 3+ adverse events, followed by pembrolizumab plus axitinib, nivolumab plus cabozantinib and lanvatinib plus pembrolizumab. Important differences in follow-up duration, risk group composition and nephrectomy rates distinguish the four studies. CONCLUSIONS: Nivolumab plus cabozantinib combination may provide the most favorable OS. Conversely, lenvatinib plus pembrolizumab may provide the most favorable PFS and ORRs, while nivolumab plus ipilimumab the lowest toxicity. However, important population differences may potentially undermine the generalizability and the robustness of these findings. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e676-e677 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luigi Nocera More articles by this author Pierre Karakiewicz More articles by this author Mike Wenzel More articles by this author Shahrokh Shariat More articles by this author Fred Saad More articles by this author Felix Chun More articles by this author Alberto Briganti More articles by this author Anil Kapoor More articles by this author Aly-Khan Lalani More articles by this author Alberto Martini More articles by this author Alessandro Larcher More articles by this author Luigi Candela More articles by this author Antony Pellegrino More articles by this author Giuseppe Fallara More articles by this author Gianfranco Baiamonte More articles by this author Cristina Giancristofaro More articles by this author Roberto Bertini More articles by this author Andrea Necchi More articles by this author Francesco Montorsi More articles by this author Umberto Capitanio More articles by this author Expand All Advertisement Loading ...

Prognostic and predictive impact of creatine kinase level in non-small cell lung cancer treated with tyrosine kinase inhibitors.

BackgroundThe use of tyrosine kinase inhibitors (TKIs) is associated with incident creatine kinase (CK) elevation in the treatment of advanced non-small cell lung cancer (NSCLC) patients. However, whether higher CK levels are associated with better antitumor responses or survival remains to be explored. We intend to investigate the clinical correlation between CK levels and TKI efficacy in advanced NSCLC.MethodsIn this retrospective study, we enrolled 135 patients with stage IV NSCLC receiving TKI-based therapy in our center between June 2012 to July 2020. CK levels were monitored from the initiation of TKI medication and during the administration period. An X-tile analysis provided the optimal cutoff point for higher baseline CK. Patients were identified and grouped according to their baseline CK level and fold changes during TKI therapy. The primary endpoints included progression-free survival (PFS) and overall survival (OS), and the objective response rate (ORR) was calculated as the secondary endpoint.ResultsAmong the 135 patients included in our study, those with higher baseline CK levels (≥70 U/L) had favorable PFS (15.2 vs. 8.8 months; P=0.028), while patients with significantly elevated CK (the highest CK value/baseline CK value ≥2 times) appeared to gain better PFS (14.6 vs. 10.0 months; P=0.139). The overall ORR was 67.4%. Patients with higher baseline CK levels had numerically higher ORR (74.6% vs. 60.3%; P=0.076). Similarly, patients with significant CK elevation had a superior 4-month PFS rate (77.6% vs. 59.7%; P=0.029). Results from the subgroup analyses were identical to the overall ones. For patients with higher baseline CK levels, those experiencing significant CK elevation had prolonged PFS (17.2 vs. 14.2 months; P=0.038); a same trend was obtained from the lower baseline CK group (<70 U/L) (9.4 vs. 7.9 months; P=0.038). In multivariable analysis, higher baseline CK level and significant CK elevation remained statistically associated with PFS, with hazard ratios of 0.48 and 0.59, respectively.ConclusionsBoth higher baseline CK levels and significant CK elevation after treatment were correlated with prolonged PFS in NSCLC treated with TKIs, suggesting the potential prognostic and predictive impact of CK level on these patients.

MP26-04 STANDARDIZED UPTAKE VALUES AS DETERMINED ON PROSTATE-SPECIFIC MEMBRANOUS ANTIGEN POSITRON EMISSION TOMOGRAPHY/COMPUTER TOMOGRAPHY ARE ASSOCIATED WITH GLEASON GRADE AND BIOCHEMICAL RECURREANCE OF DISEASE IN PATIENTS WITH PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Detection & Screening II (MP26)1 Sep 2021MP26-04 STANDARDIZED UPTAKE VALUES AS DETERMINED ON PROSTATE-SPECIFIC MEMBRANOUS ANTIGEN POSITRON EMISSION TOMOGRAPHY/COMPUTER TOMOGRAPHY ARE ASSOCIATED WITH GLEASON GRADE AND BIOCHEMICAL RECURREANCE OF DISEASE IN PATIENTS WITH PROSTATE CANCER Yves Bodar, Hans Veerman, Katelijne de Bie, Dennie Meijer, Pim van Leeuwen, Maarten Donswijk, Harry Hendrikse, Ronald Boellaard, Daniela Oprea-Lager, and André Vis Yves BodarYves Bodar More articles by this author , Hans VeermanHans Veerman More articles by this author , Katelijne de BieKatelijne de Bie More articles by this author , Dennie MeijerDennie Meijer More articles by this author , Pim van LeeuwenPim van Leeuwen More articles by this author , Maarten DonswijkMaarten Donswijk More articles by this author , Harry HendrikseHarry Hendrikse More articles by this author , Ronald BoellaardRonald Boellaard More articles by this author , Daniela Oprea-LagerDaniela Oprea-Lager More articles by this author , and André VisAndré Vis More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002023.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) staging has been improved by prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PSMA-PET/CT). Intraprostatic PSMA intensity, as measured by standardized uptake values (SUV), could predict clinically relevant oncological outcomes for PCa. This study aims to investigate the correlation between SUV in patients with PCa prior to radical prostatectomy (RP) and adverse pathology outcomes, including Gleason score (GS), pN1 status and biochemical progression-free survival (PFS). METHODS: A total of 318 patients with biopsy-proven PCa scheduled for RP with a pelvic lymph node dissection in 84.5%, (269/318 patients) were retrospectively analysed (median PSA: 10.5 ng/ml). Prior to RP, patients received a PET/CT with either 68Ga-PSMA (189/318 (59%) patients) or 18F-DCFPyL-PSMA (129/318 (41%) patients). PET/CT images were analysed visually and semi-quantitatively by measuring the maximum SUV (SUVmax) of the most intense suspect lesion in the prostate. The SUVmax of the primary tumour was assessed in relation to GS, pN1 status and PFS. RESULTS: Patients with PCa tumours with a GS of ≤7 showed significantly lower SUVmax compared to patients with GS >7 for both tracers (SUVmax F18: 7.4 versus 14.5; p<0.001, SUVmax Ga68: 7.3 versus 9.3; p=0.01). Moreover, PCa patients with positive lymph nodes on pathology examination exhibited significantly higher median uptake than those without for both tracers (SUVmax F18: 7.9 versus 12.3; p=0.04, SUVmax Ga68: 7.6 versus 12.0 p<0.001). Of the total cohort, 77.6% (247/318) of patients were free from progression at a median follow-up of 11.6 months (Range 1.4–32.8 months). As shown in figure 1, the pooled lower quartiles of SUVmax for both tracers showed a favourable PFS versus the upper 2 quartiles (p<0.001). CONCLUSIONS: Intraprostatic PSMA-PET/CT intensity, as measured by SUVmax is prognostic and may be a valuable new biomarker in localised PCa. The GS, pN1 status and PFS correlated with the intensity of tracer accumulation in the primary tumours of PC patients on PSMA PET/CT with both the 68Ga-PSMA and 18F-DCFPyL-PSMA tracers. Source of Funding: n/a © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e463-e463 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yves Bodar More articles by this author Hans Veerman More articles by this author Katelijne de Bie More articles by this author Dennie Meijer More articles by this author Pim van Leeuwen More articles by this author Maarten Donswijk More articles by this author Harry Hendrikse More articles by this author Ronald Boellaard More articles by this author Daniela Oprea-Lager More articles by this author André Vis More articles by this author Expand All Advertisement Loading ...

Peritumoral edema status of glioblastoma identifies patients reaching long-term disease control with specific progression patterns after tumor resection and high-dose proton boost

BackgroundGlioblastoma peritumoral edema (PE) extent is associated with survival and progression pattern after tumor resection and radiotherapy (RT). To increase tumor control, proton beam was adopted to give high-dose boost (> 90 Gy). However, the correlation between PE extent and prognosis of glioblastoma after postoperative high-dose proton boost (HDPB) therapy stays unknown. We intend to utilize the PE status to classify the survival and progression patterns.MethodsPatients receiving HDPB (96.6 GyE) were retrospectively evaluated. Limited peritumoral edema (LPE) was defined as PE extent < 3 cm with a ratio of PE extent to tumor maximum diameter of < 0.75. Extended progressive disease (EPD) was defined as progression of tumors extending > 1 cm from the tumor bed edge.ResultsAfter long-term follow-up (median 88.7, range 63.6–113.8 months) for surviving patients with (n = 13) and without (n = 32) LPE, the median overall survival (OS) and progression-free survival (PFS) were 77.2 vs. 16.7 months (p = 0.004) and 13.6 vs. 8.6 months (p = 0.02), respectively. In multivariate analyses combined with factors of performance, age, tumor maximum diameter, and tumor resection extent, LPE remained a significant factor for favorable OS and PFS. The rates of 5-year complete response, EPD, and distant metastasis with and without LPE were 38.5% vs. 3.2% (p = 0.005), 7.7% vs. 40.6% (p = 0.04), and 0% vs. 34.4% (p = 0.02), respectively.ConclusionsThe LPE status effectively identified patients with relative long-term control and specific progression patterns after postoperative HDPB for glioblastoma.

SPARC-positive macrophages are the superior prognostic factor in the microenvironment of diffuse large B-cell lymphoma and independent of MYC rearrangement and double-/triple-hit status

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with respect to outcome. Features of the tumor microenvironment (TME) are associated with prognosis when assessed by gene expression profiling. However, it is uncertain whether assessment of the microenvironment can add prognostic information to the most relevant and clinically well-established molecular subgroups when analyzed by immunohistochemistry (IHC). We carried out a histopathologic analysis of biomarkers related to TME in a very large cohort (n= 455) of DLBCL treated in prospective trials and correlated with clinicopathologic and molecular data, including chromosomal rearrangements and gene expression profiles for cell-of-origin and TME. The content of PD1+, FoxP3+ and CD8+, as well as vessel density, was not associated with outcome. However, we found a low content of CD68+ macrophages to be associated with inferior progression-free survival (PFS) and overall survival (OS; P= 0.023 and 0.040, respectively) at both univariable and multivariable analyses, adjusted for the factors of the International Prognostic Index (IPI), MYC break and BCL2/MYC and BCL6/MYC double-hit status. The subgroup of PDL1+ macrophages was not associated with survival. Instead, secreted protein acidic and cysteine rich (SPARC)-positive macrophages were identified as the subtype of macrophages most associated with survival. SPARC-positive macrophages and stromal cells directly correlated with favorable PFS and OS (both, P[log rank] <0.001, P[trend] < 0.001). The association of SPARC with prognosis was independent of the factors of the IPI, MYC double-/triple-hit status, Bcl2/c-myc double expression, cell-of-origin subtype and a recently published gene expression signature [lymphoma-associated macrophage interaction signature (LAMIS)]. SPARC expression in the TME detected by a single IHC staining with fair-to-good interobserver reproducibility is a powerful prognostic parameter. Thus SPARC expression is a strong candidate for risk assessment in DLBCL in daily practice.

Prognostic significance of human papillomavirus 16 viral load level in patients with oropharyngeal cancer.

Human papillomavirus (HPV) infection in patients with oropharyngeal squamous cell carcinoma (OPSCC) is a major determinant for better prognosis. However, there remain HPV‐positive patients who have poor outcomes. The stratification strategy for detecting high‐risk patients among those with HPV‐positive OPSCC has not been well delineated, especially for Asian patients. We undertook a retrospective cohort study on the survival rate of 89 Japanese patients diagnosed with primary OPSCC. The tumors were concurrently analyzed for the presence of HPV E6 DNA/mRNA, viral DNA load, p16 expression, viral physical status, and viral variant lineage. Human papillomavirus 16 viral DNA was found in 45 (51%) OPSCCs. Human papillomavirus 16 DNA‐positive OPSCCs with higher viral load (classified as HPV16 DNA‐medium/high OPSCCs) showed significantly favorable overall survival and progression‐free survival compared with HPV16 DNA‐positive OPSCCs with lower viral load (<10 copies/cell; HPV16 DNA‐low OPSCCs) and HPV16 DNA‐negative OPSCCs. E6 mRNA expression was observed in all HPV16 DNA‐medium/high OPSCCs but not in HPV16 DNA‐low OPSCCs. Notably, p16‐positive and HPV16 DNA‐negative/low OPSCCs showed significantly worse survival than p16‐positive and HPV16 DNA‐medium/high OPSCCs and resembled HPV‐unrelated OPSCCs with regard to survival and risk factor profile. Although not significant, a trend toward shorter survival was observed for HPV16‐integrated OPSCCs. Phylogenetic analysis revealed two major types of HPV16 variants termed Asian (A4) and European (A1/A2/A3) variants, but no difference in survival between these variants was observed. Altogether, these findings suggest that HPV viral load is a potentially informative factor for more accurate risk stratification of patients with OPSCC.

Single-nucleotide Fcγ receptor polymorphisms do not impact obinutuzumab/rituximab outcome in patients with lymphoma

AbstractSingle-nucleotide polymorphisms (SNPs) have been shown to influence Fcγ receptor (FcγR) affinity and activity, but their effect on treatment response is unclear. We assessed their importance in the efficacy of obinutuzumab or rituximab combined with chemotherapy in untreated advanced follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) in the GALLIUM (www.clinicaltrials.gov #NCT01332968) and GOYA (#NCT01287741) trials, respectively. Genomic DNA was extracted from patients enrolled in GALLIUM (n = 1202) and GOYA (n = 1418). Key germline SNPs, FCGR2A R131H (rs1801274), FCGR3A F158V (rs396991), and FCGR2B I232T (rs1050501), were genotyped and assessed for their impact on investigator-assessed progression-free survival (PFS). In both cohorts there was no prognostic effect of FCGR2A or FCGR3A. In FL, FCGR2B was associated with favorable PFS in univariate and multivariate analyses comparing I232T with I232I, with a more modest association for rituximab-treated (univariate: hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.54-1.14; P = .21) vs obinutuzumab-treated patients (HR, 0.56; 95% CI, 0.34-0.91; P = .02). Comparing T232T with I232I, an association was found for obinutuzumab (univariate: HR, 2.76; 95% CI, 1.02-7.5; P = .0459). Neither observation retained significance after multiple-test adjustment. FCGR2B was associated with poorer PFS in multivariate analyses comparing T232T with I232I in rituximab- but not obinutuzumab-treated patients with DLBCL (HR, 4.40; 95% CI, 1.71-11.32; P = .002; multiple-test–adjusted P = .03); however, this genotype was rare (n = 13). This study shows that FcγR genotype is not associated with response to rituximab/obinutuzumab plus chemotherapy in treatment-naive patients with advanced FL or DLBCL.

CD19/CD22 Dual-Targeted CAR T-cell Therapy for Relapsed/Refractory Aggressive B-cell Lymphoma: A Safety and Efficacy Study.

Chimeric antigen receptor (CAR) T-cell therapies that target either CD19 or CD22 alone have potent antilymphoma effects. However, antigen escape-mediated relapse often occurs. CAR T cells targeting both CD19 and CD22 may overcome this limitation. In this study, we developed bispecific CAR T cells simultaneously recognizing CD19- and CD22-expressing targets and assessed their safety and efficacy profiles in patients with relapsed/refractory aggressive B-cell lymphoma. Twenty-four patients were screened, and 16 were found eligible for the study. CAR T-cell-associated toxicities were recorded. Responses, overall survival (OS), and progression-free survival (PFS) were assessed. Of the 16 eligible patients, 14 (87.5%) achieved objective response and 10 (62.5%) achieved complete response (CR). The 2-year OS and PFS rates were 77.3% and 40.2%, respectively. Achieving CR (P = 0.046) and the number of prior chemotherapy lines (n = 2; P = 0.047) were independent prognostic factors associated with favorable PFS. The 2-year OS and PFS among patients who achieved CR were higher than among those who did not (P = 0.015 and P < 0.001, respectively). The 2-year PFS among patients who received two prior lines of chemotherapy was higher than that among patients who received more than two lines of chemotherapy (P = 0.049); OS did not differ between the groups. Severe grade 4 cytokine-release syndrome (CRS) was observed in 1 patient; 4 and 11 patients had grades 1 and 2 CRS, respectively. No patients developed neurotoxicity. CD19/CD22 dual-targeted CAR T cells may be a safe, potent antilymphoma cell-based targeted immunotherapy.