Significant Difference In Progression-free Survival Research Articles

Comparison of efficacy between anti-PD-1 antibody monotherapy and nivolumab plus ipilimumab therapy as first-line immunotherapy for advanced mucosal melanoma in Japanese patients: A single-center, retrospective cohort study.

Mucosal malignant melanoma (MMM) is a rare subtype of malignant melanoma with a more aggressive biological behavior than cutaneous melanoma (CM). Owing to its rarity, it is necessary to accumulate information on treatments, especially in Asians, in whom MMM occurs more frequently than in Caucasians. In this study, we investigated the efficacy and adverse events (AEs) of nivolumab plus ipilimumab therapy (NIVO+IPI) versus immune checkpoint inhibitor (ICI) monotherapy (PD-1) in Japanese patients with MMM. We reviewed patients with advanced or recurrent MMM who received ICIs as first-line systematic therapy between February 2012 and February 2024 at the Shizuoka Cancer Center. We enrolled a total of 57 patients: 10 (17.5%) were treated with NIVO+IPI, and 47 (82.5%) were treated with PD-1 as first-line systemic therapy. Objective response rates (ORR) did not differ significantly between the NIVO+IPI and PD-1 groups (40.0% vs 27.7%; p = 0.176). There was also no statistically significant difference in progression-free survival (PFS) (median PFS time: 4.3 months vs 9.9 months, log-rank test, p = 0.578) or overall survival (OS) (median OS time: 33.1 months vs. 22.8 months, log-rank test, p = 0.697) between the two groups. However, regarding AEs, grade ≥3 AEs leading to discontinuation of first-line treatment occurred in 80% of patients in the NIVO+IPI group and in 22.6% of patients in the PD-1 group (p = 0.002). No difference was found in the efficacy of NIVO+IPI therapy and anti-PD-1 antibody monotherapy as the first-line treatment for MMM in Japanese patients, but an increase in AEs was observed with combination therapy. This study suggests that patients with MMM may receive less benefit from NIVO+IPI than from PD-1.

Efficacy of PARP inhibitors in advanced high-grade serous ovarian cancer according to BRCA domain mutations and mutation type.

Preclinical studies have emphasized the potential connection between BRCA specific domains defects and the activity of Poly ADP-ribose polymerase inhibitors (PARPi). Nevertheless, real-world evidence regarding the impact of BRCA domain defects and mutations on PARPi efficacy are limited. The aim of his study was to evaluate the efficacy of PARPi in terms of progression free survival (PFS) according to BRCA domains defects and mutation types. A retrospective analysis was performed among 79 BRCA mutated patients, diagnosed with advanced High-grade serous ovarian carcinoma (HGSOC) who received first- and second-line platinum- based chemotherapy followed by PARPi maintenance treatment. PFS was evaluated according to BRCA1 [Really Interesting Gene (RING), DNA Binding (DBD), Serine Cluster (SCD), BRCA1 C-terminal (BRCT)] and BRCA2 [RAD-51 Domain (RAD-51 BD), DBD] specific domain defects and mutation types [missense (MS), nonsense (NS), frameshift (FS), splicing (S), or large rearrangements (LR)]. After a median follow-up of 51 months, no significant difference in PFS was observed between the BRCA functional domains or mutation types in the BRCA1 and BRCA2 subgroups. Patients with BRCA2 DBD and RAD51-BD defects had the longest (39.8 months) and shortest (24.1 months) median PFS, respectively (p = 0.11). Additionally, patients with BRCA1 DBD defects had the greatest benefit (median PFS = 33.8 months) while those with BRCA1 RING domain mutations experienced the worst outcome (median PFS = 30.9 months (p = 0.43). The efficacy of maintenance treatment with PARPi is independent by BRCA domain defects or mutation types. Patients DBD domain defects experienced numerically longer median PFS compared to those with other BRCA1/2 alterations.

Clinical outcomes of first-line combination therapy with immune checkpoint inhibitor for metastatic non-clear cell renal cell carcinoma: a multi-institutional retrospective study in Japan.

In metastatic clear cell renal cell carcinoma (ccRCC), recent studies have shown promising efficacy of immune checkpoint inhibitor (ICI) combination therapy. However, there are insufficient evidences about clinical efficacy and safety of ICI combination therapy in metastatic non-ccRCC (nccRCC). We retrospectively investigated 44 patients treated with nivolumab plus ipilimumab (ICI + ICI group) or anti-PD-1/PD-L1 inhibitor plus tyrosine kinase inhibitors (TKI) (ICI + TKI group), and assessed clinical efficacy in both groups. Of all patients, overall response rate and disease control rate for ICI combination treatments were 36.3% and 75%, respectively. The median progression-free survival (PFS) and overall survival (OS) was 8.8 and 23.9months, respectively. Multivariate analysis revealed that the presence of liver metastasis significantly affected worse PFS and OS (p = 0.035 and p = 0.049). Importantly, PFS and OS seemed similar in ICI + ICI group and ICI + TKI group (p = 0.778 and p = 0.559). Although the discontinuation rate of the combination therapy due to adverse effects in patients aged ≥ 75years was significantly higher compared to that in patients aged < 75years (45% versus 12%, p = 0.017), there were no significant differences in PFS and OS between two groups (p = 0.290 and p = 0.257, respectively). This study confirms clinical benefit of ICI combination therapy for metastatic nccRCC patients in real-world settings. Furthermore, the effectiveness of combination therapy was comparable between patients aged < 75 and those ≥75years with respect to clinical prognosis.

Prognostic Study of Inflammatory Markers in Nasopharyngeal Carcinoma Patients Receiving Intensity-Modulated Radiotherapy.

Inflammatory markers in the blood have been linked to tumor prognosis, but their specific prognostic significance in nasopharyngeal carcinoma (NPC) patients undergoing intensity-modulated radiotherapy (IMRT) is not well established. This study aims to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in this patient population. A total of 406 non-metastatic NPC patients were included in the study. NLR, PLR, and LMR were stratified according to their average values. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Cox multivariate regression analysis was performed to evaluate the associations of NLR, PLR, and LMR with PFS and OS. Patients with NLR > 2.78had worse PFS (P = 0.008) and OS (P < 0.001); PLR > 162.48 was related to lower PFS (P = 0.018) but not OS (P = 0.29); LMR > 5.05 showed no significant difference in PFS and OS compared to LMR ≤ 5.05 (P values were 0.13 and 0.94, respectively). Multivariate analysis indicated that NLR was an independent prognostic factor for PFS (HR, 1.674; 95% CI, 1.006-2.784; P = 0.047) and OS (HR, 4.143; 95% CI, 2.111-8.129; P = 0.000), while PLR and LMR did not demonstrate significant associations with PFS and OS. This study identifies NLR as a novel and independent prognostic indicator for NPC patients receiving IMRT, offering valuable insights that could inform future clinical decision-making. In contrast, PLR and LMR did not demonstrate significant prognostic value in this context.

Regorafenib combined with immune checkpoint inhibitors versus regorafenib monotherapy as a late-line treatment for metastatic colorectal cancer: a single-center, retrospective cohort study.

Few data are available on metastatic colorectal cancer (mCRC) treated with late-line regorafenib monotherapy or combined with other therapies. This study thus aimed to examine regorafenib combined with immune checkpoint inhibitors (ICIs) compared with regorafenib monotherapy in patients with advanced CRC. This single-center retrospective cohort study included patients with advanced CRC who experienced recurrence and progression after standard first- and second-line treatments treatment from November 2018 to December 2021. The patients received regorafenib plus ICIs or regorafenib monotherapy. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST). Overall survival (OS) and progression-free survival (PFS) were analyzed via multivariate analysis. The combined group and the monotherapy group included 30 and 43 patients, respectively. The median OS (13.7 vs. 10.1 months; P=0.10) and PFS (4 vs. 3.6 months; P=0.32) were not significantly different between the two groups. In males, the median OS was significantly longer in the combined group compared with the monotherapy group (not reached vs. 8.03 months; P=0.02), but the median PFS showed no significant difference (7.23 vs. 3.90 months; P=0.16). There was no significant difference in OS (P=0.71) or PFS (P=0.89) in females. Eastern Cooperative Oncology Group performance status (ECOG PS) 1 [vs. 0; hazard ratio (HR) =3.13, 95% confidence interval (CI): 1.61-6.10; P<0.001] was independently associated with PFS. ECOG PS 1 (vs. 0; HR =3.63, 95% CI: 1.54-8.56; P=0.003) and combined therapy (vs. monotherapy; HR =0.47, 95% CI: 0.22-0.99; P=0.048) were associated with OS. Regorafenib combined with ICIs led to numerically longer PFS and significantly prolonged OS in patients with mCRC compared to regorafenib monotherapy, especially in male patients.

Radiotherapy with S-1 for the treatment of esophageal squamous cell carcinoma 75 years or older

ObjectiveExplore the efficacy and safety of involved-field irradiation (IFI) combined with S-1 as definitive concurrent chemoradiotherapy (dCRT) for locally advanced elderly esophageal squamous cell carcinoma (ESCC), under the premise of intensity-modulated radiotherapy (IMRT).MethodsWe designed a prospective single-arm phase II study. The study enrolled 91 patients aged 75 to 92 years. Eligible participants had histologically confirmed squamous cell carcinoma, stage II to IV disease based on the 8th edition of the American Joint Committee on Cancer (AJCC). All elderly patients (EPs) received dCRT with S-1. which was administered orally twice daily for 28 days. The radiotherapy dose was 61.2 Gy delivered in 34 fractions or 50.4 Gy delivered in 28 fractions. The primary endpoint was 2-year overall survival (OS), and the secondary endpoints were progression-free survival (PFS), local control rate (LCR), and safety.ResultsFrom July 2017 to July 2021, we enrolled EPs with ESCC who were treated at the Jiangsu Cancer hospital. As of August 1, 2023, the median follow-up of surviving EPs was 31.4 months (IQR: 25.2 to 72.6 months). 83 patients (91.2%) completed the whole course of treatment. The 2-year OS rate was 59.2%, and the PFS rate was 43.7%. The most common grade 1 to 2 adverse effects (AEs) were radiation esophagitis (79.1%), and then were radiation pneumonia (46.2%). Anemia (41.8%) was the most common of grade 1 to 2 hematologic toxicity. The incidence of grade 3 or above AEs was 24.2%, and the incidence of leukopenia was the highest (11.0%). There was not one death due to treatment-related toxicity. In a subgroup analysis of radiotherapy doses, we found no statistically significant differences in PFS (P = 0.465) and OS (P = 0.345) in EPs with ESCC who received 50.4 Gy and 61.2 Gy, and that patients in the 50.4 Gy group had lower dermatitis (P = 0.045) and anemia (P = 0.004).ConclusionsIF-IMRT combined with S-1 is a promising regimen for elderly ESCC. And the radiotherapy dose of 50.4 Gy remains the standard dose for EPs with ESCC undergoing CCRT.

Baseline genetic abnormalities and effectiveness of osimertinib treatment in patients with chemotherapy-naïve EGFR-mutated NSCLC based on performance status

Background/AimFor patients treated with osimertinib as first-line therapy, there have been no studies comparing both progression-free survival (PFS) and overall survival (OS) according to performance status (PS). Furthermore, no studies have examined differences in baseline genetic abnormalities between patients with poor and good PS. Therefore, we aimed to investigate differences in baseline genetic abnormalities and treatment effects between patients with poor and good PS who received osimertinib as the primary treatment.Patients and methodsThis is a secondary analysis of the ELUCIDATOR study, which is a multi-center prospective observational study in Japan that assessed mechanisms underlying resistance to osimertinib as first-line treatment for advanced non-small cell lung cancer with epidermal growth factor receptor mutations.ResultsThere were 153 and 25 patients in the good and poor PS groups, respectively. Multivariate analysis revealed no significant between-group differences in PFS (hazards ratio [HR]: 0.98, 95% confidence interval [CI]: 0.52–1.72, p = 0.946). Multivariate analysis of OS revealed that poor PS was a poor prognostic factor (HR: 2.67, 95% CI: 1.43–4.73, p = 0.003). Regarding baseline genetic abnormalities, there was a significant increase in APC-positive cases (20.0% vs. 2.2%, p = 0.009) and a trend toward more CTNNB1-positive cases in the poor PS group than in the good PS group (14.3% vs. 2.9%, p = 0.062).ConclusionThere was no between-group difference in PFS, although OS was significantly inferior in the poor PS group. Additionally, there was a significant increase in APC-positive cases and a trend toward more CTNNB1-positive cases in the poor PS group.

Clinical outcomes and prognostic factors in metastatic nonclear cell renal cell carcinoma treated with immuno-oncology combination therapy.

Metastatic nonclear cell renal cell carcinoma (nccRCC) is a heterogeneous disease with poor prognosis. The clinical characteristics and prognostic factors of immuno-oncology (IO) combination therapy for nccRCC are not well known. This study analyzed patients with metastatic nccRCC treated with IO combination therapy. We retrospectively collected data from 447 patients with metastatic RCC treated with IO-based combination therapy as first-line treatment between September 2018 and July 2023 in a Japanese multicenter study. The primary endpoints were objective response rate, progression-free survival (PFS), and overall survival (OS), comparing groups treated with IO-IO and IO-tyrosine kinase inhibitor (TKI) therapies. Seventy-five patients with metastatic nccRCC were eligible for analysis: 39 were classified into the IO-IO group and 36 into the IO-TKI group. Median PFS was 5.4months (95% CI: 1.6-9.1) for the IO-IO group and 5.6 (95% CI: 3.4-12.0) for the IO + TKI group. Median OS was 24.2months (95% CI: 7.5-NA) for the IO-IO group and 23.4 (95% CI: 18.8-NA) for the IO + TKI group, with no significant difference. In univariate analysis, International Metastatic Renal Cell Carcinoma Database Consortium scores, Karnofsky performance status, neutrophil-to-lymphocyte ratio, and the presence of liver metastases were significantly associated with OS, whereas in multivariate analysis, only the presence of liver metastases was significantly associated with OS (P = .035). There was no significant difference in OS or PFS between IO-IO and IO-TKI combination therapy as first-line treatment for patients with nccRCC. Liver metastasis is a poor prognostic factor for such patients.

Factors Affecting an Increase in Spleen Volume and Association of Spleen Volume Variation with the Clinical Outcomes of Atezolizumab and Bevacizumab Treatment for Hepatocellular Carcinoma: A Retrospective Analysis

Plain Language SummaryImmunotherapy is now the standard of care for systemic therapy in hepatocellular carcinoma (HCC). The combination of atezolizumab and bevacizumab (Atez/Bev) is recommended for the first-line treatment, while gastrointestinal varices rupture is likely to be observed during Atez/Bev. Gastrointestinal varices rupture is a fatal event and developed due to portal hypertension. Spleen volume (SpV) plays an important role in portal hypertension based on previous studies, and we examined variation in SpV during Atez/Bev treatment and investigated predictive factors that affect the increase in SpV and the association of SpV variation and pretreatment SpV with the clinical outcome of Atez/Bev. The median pretreatment SpV was 184 (130–257) cm3 and the median SpV variation was 27 (9–60) cm3. An increase in the SpV was observed in 140 patients (85.4%). Age <74 years (p = 0.03), mALBI grade 2b or 3 (p = 0.03), and pretreatment SpV ≥184 cm3 (p < 0.001) were significantly associated with increased SpV. The present study revealed that there were no significant differences in progression-free survival and overall survival between patients with and without pretreatment spleen enlargement, as well as between patients with SpV variation ≥25 cm³ and those with SpV variation <25 cm³. In conclusion, caution is warranted to detect the aggravation of portal hypertension when administering Atez/Bev to young patients or those with an impaired liver function or pretreatment spleen enlargement. The impact of spleen modulation by Atez/Bev appears to be limited on clinical efficacy.

Comparative effectiveness analysis of survival with first-line palbociclib or ribociclib plus AI in HR + /HER2- advanced breast cancer (CEPRA study): preliminary analysis of real-world data from Thailand

BackgroundThe current standard first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR + /HER2 −) advanced breast cancer (ABC) is a combination of aromatase inhibitor (AI) plus CDK4/6 inhibitors (CDK4/6i). Direct comparison trials of different CDK4/6i are scarce. This real-world study compared the effectiveness of first-line AI plus ribociclib versus palbociclib.MethodsThis multicenter retrospective cohort study, conducted in six cancer centers in Thailand, enrolled patients with HR + /HER2 − ABC treated with first-line AI, and either ribociclib or palbociclib. Propensity score matching (PSM) was performed. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), time to chemotherapy (TTC), and adverse events.ResultsOf the 250 patients enrolled, 134 patients with ribociclib and 49 patients with palbociclib were captured after PSM. Baseline characteristics were well-balanced between groups. Median PFS in patients receiving ribociclib and palbociclib were 27.9 and 31.8 months, respectively (hazard ratio: 0.87; 0.55–1.37). The median OS in the AI + ribociclib arm was 48.7 months compared to 59.1 months in the AI + palbociclib arm (hazard ratio: 0.55; 0.29–1.05). The median TTC in the AI + palbociclib group was 56 months, but not reached in the AI + ribociclib group (p = 0.42). The ORR of AI + ribociclib and AI + palbociclib were comparable (40.5% vs. 53.6%, p = 0.29). Patients receiving palbociclib demonstrated a higher proportion of neutropenia compared to those receiving ribociclib, despite a similar dose reduction rate (p = 0.28). Hepatitis rate was similar between the ribociclib (21%) and palbociclib groups (22%). Additionally, a low incidence of QT prolongation was observed in both the ribociclib (5%) and palbociclib groups (4%).ConclusionThis preliminary analysis of a real-world study demonstrated the comparable effectiveness of ribociclib and palbociclib with AI as an initial therapy for HR + /HER2 − ABC. No statistically significant difference in PFS, OS, and TTC was found in patients treated with AI combined with palbociclib or ribociclib. Longer follow-up and further prospective randomized head-to-head studies are warranted.

Liver Oligometastasis in Biliary Tract Cancer and Impact on Survival Outcomes.

Outcomes of unresectable biliary tract cancer (BTC) with varying extents of liver involvement remain unclear. We evaluated characteristics and outcomes of BTC patients with liver metastases who underwent chemotherapy. We retrospectively reviewed consecutive BTC patients with synchronous or metachronous intrahepatic metastases who started first-line chemotherapy at our institution between January 2016 and December 2021. Ninety-six patients were included, of which 57 only had liver metastases and 39 had multiorgan involvement. The liver only group had longer median overall survival (OS) (11.8 vs. 7.4months, P = 0.006) and median progression-free survival (PFS) (4.1 vs. 2.7months, P = 0.035) than the multiorgan group. Patients with oligometastases (defined as no more than three liver metastases) achieved longer OS than those with polymetastases (four or more liver metastases) in the entire cohort. Within the liver only group, there were no significant differences in OS or PFS between the oligometastasis and polymetastasis groups. Patients who underwent subsequent surgery had significantly longer median OS than those who did not (44.4 vs. 7.7months, P < 0.001). Age ≥ 75years, liver-only metastasis, modified Glasgow prognostic score ≥ 1 carcinoembryonic antigen ≥ 5μg/L, and subsequent surgery were independent predictors of OS. Liver oligometastasis was only a significant predictor of longer OS in univariate Cox analysis. Outcomes in BTC patients with metastases limited to the liver, particularly those with oligometastasis, were more favorable than those with multiorgan metastases. Selected cases, generally with liver oligometastases, may achieve prolonged OS through subsequent surgery.

Optimizing Surgical Outcomes for Intracranial Epidermoid Tumors: A Retrospective Analysis of Clinical Predictors, Surgical Decisions, and Patient Clustering

IntroductionIntracranial epidermoid tumors (ETs) are rare, benign lesions that present significant challenges in neurosurgical management due to their propensity to encase vital neurovascular structures. ObjectiveTo evaluate the impact of clinical, demographic, and tumor-specific factors on surgical decisions (gross total resection [GTR] vs. subtotal resection [STR]) and outcomes and identify patient clusters with distinct profiles and outcomes post-resection. MethodsWe retrospectively analyzed 72 epidermoid brain tumor patients treated from 1998 to 2022, employing multivariable logistic regression for GTR vs. STR predictors and Kaplan-Meier curves for progression-free survival (PFS). K-prototype clustering classified patients based on clinical data. ResultsThe mean age of our cohort was 39.8±20.1 years. 13.9% of patients had a recurrence, with a median PFS of 108 months (IQR 57-206). Seizures significantly predicted GTR (p<0.05), whereas adherence to critical structures reduced GTR likelihood (p<0.05). Initial surgeries more often achieved GTR, correlating with longer PFS (p<0.0001) and reduced recurrence (p<0.01). History of previous ET surgery was predictive of increased recurrent tumor size (p<0.05) and reduced overall PFS (p<0.05). Clustering analysis revealed three clusters with significant differences in recurrence rates (p<0.0001), long term neurological deficits (p<0.05), PFS greater than 10 years (p<0.0001), and significant differences in median PFS between clusters 1 and 3 (p<0.0001) as well as 2 and three (p<0.01). ConclusionThis study emphasizes the importance of tailored surgical strategies in managing intracranial ETs, advocating for GTR to optimize long-term outcomes where possible. Future prospective studies are essential to further refine treatment approaches, enhancing survival for ET patients.

Real-world experience with CDK4/6 inhibitors in hormone receptor-positive metastatic and recurrent breast cancer: findings from an Asian population

PurposeCyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy have demonstrated significant clinical benefits in progression-free and overall survival. This study investigates the outcomes associated with two kinds of CDK4/6i in patients with hormone receptor (HR)-positive metastatic and relapsed breast cancer to inform real-world evidence of treatment strategies.MethodsThis retrospective study included 340 Taiwanese patients with HR-positive advanced breast cancer from the Taipei Veterans General Hospital, between 2018 and 2023. We analyzed patient characteristics, treatment strategies and outcomes associated with two CDK4/6i. The efficacy of patients who experienced economic burden and interrupted CDK4/6i treatment after 2 years of National Health Insurance (NHI) reimbursement was also investigated.ResultsPatients receiving ribociclib and palbociclib showed no significant differences in age, histology, body mass index(BMI), or pathologic status. The distribution of disease status and endocrine therapy partners was comparable between the two groups. Dose reduction was similar, while patients with palbociclib tended to discontinue CDK4/6i usage, and those with ribociclib tended to switch to the other CDK4/6i or endocrine partners. There was no significant difference in progression-free survival (PFS) between the two CDK4/6i in the first-line setting. Adverse prognostic factors were increasing HER2 IHC score, higher Ki-67 levels, visceral and liver metastasis, prior chemotherapy, and endocrine therapy resistance, while higher BMI, bone-only metastasis, and letrozole treatment were associated with a lower risk of progression. The limited follow-up time in our study was insufficient to assess the outcomes of patients treated with interrupted CDK4/6i for up to two years under the NHI reimbursement policy.ConclusionTreatment outcomes between the two types of CDK4/6i did not differ significantly, indicating the safety and efficacy of CDK4/6i for the Asian population. Ribociclib and palbociclib showed similar efficacy in PFS in the real-world setting.

Programmed cell death ligand 1 (PD-L1) inhibitors versus programmed cell death 1 (PD-1) inhibitors for the first-line therapy of extensive-stage small cell lung cancer: A propensity score-matched study.

206 Background: Addition of programmed cell death ligand 1 (PD-L1) inhibitors or programmed cell death 1 (PD-1) inhibitors to etoposide‐platinum (EP) chemotherapy has become the standard first-line regimen for ES-SCLC. The clinical efficacy and safety between the two types of immune checkpoint inhibitors (ICIs) remain controversial. We conduct the retrospective study and propensity score-matched analysis to explore the potential differences between them. Methods: Patients diagnosed with ES-SCLC and treated by EP plus PD-L1 or PD-1 inhibitors at Shandong Cancer Hospital between March 2019 and November 2022 were reviewed retrospectively. According to PD-L1 or PD-1 inhibitors, they were divided into two groups. Propensity score matching (1:1) was performed to balance the baseline characteristics of the two groups. The baseline characteristics and adverse events between the two groups were compared using the chi-squared test. The survival curves of overall survival (OS) and progression-free survival (PFS) were plotted by the Kaplan-Meier method and differences were analyzed by the log-rank test.The primary endpoints were OS and PFS. Results: As a result, 448 patients were analyzed in this study. 264 patients received PD-L1 inhibitors plus EP and 184 received PD-1 inhibitors plus EP. The median follow-up was 17.6 months. The median OS and PFS was 20.4 months and 7.8 months in the overall population. Before propensity score matching, the median OS was 20.1 months in PD-L1 inhibitor plus EP group and 20.7 months in PD-1 inhibitor plus EP group, respectively (HR 1.043, 95%CI 0.776-1.401; p= 0.781). The median PFS was 7.6 months in the PD-L1 inhibitor plus EP group and 8.5 months in PD-1 inhibitor plus EP group (HR 1.099, 95%CI 0.886-1.364; p= 0.390). After propensity score matching, the median OS and PFS were 20.4 months and 7.8months in PD-L1 inhibitor plus EP group, and those were 20.1 months and 8.6 months in PD-1 inhibitor plus EP group. There was no significant difference in OS and PFS between PD-L1 inhibitors plus EP and PD-1 inhibitors plus EP in the matched population (HR 1.104; p= 0.578 and HR 1.072; p= 0.602, respectively). The overall adverse events were comparable in the two groups. Only ≥3 grade neutropenia was more frequent in the PD-L1 inhibitors plus EP group (77.7% vs 69.0%, p= 0.040). Conclusions: In conclusion, the overall efficacy and safety profile was similar between PD-L1 inhibitors and PD-1 inhibitors for the first-line treatment of ES-SCLC.

A red blood cell-based score in the prognostication of patients with metastatic RCC of the Meet-URO 15 study.

Aims: Anemia, mean corpuscular volume and red cell distribution width may have some effects on survival outcomes of metastatic renal cell carcinoma (mRCC) patients and are incorporated in a red blood cell (RBC)-based score. Its validity in prognostication of mRCC patients treated with second-line nivolumab was assessed.Patients and methods: Retrospective analysis using Meet-URO-15 cohort of mRCC patients receiving nivolumab in the second-line setting or beyond. Outcomes were overall survival (OS) and progression-free survival (PFS).Results: A total of 390 patients were included. Significant differences in OS and PFS between RBC-based score groups, with group 1 (2 or 3 of the RBC-related prognostic factors) having longer OS (median 29.5months, 95% CI: 23.1-35.9, versus 11.5months, 95% CI: 8.5-22.6; p<0.001) and PFS (7.5months, 95% CI: 5.5-10.2, versus 4.2months, 95% CI: 3.3-5.9; p=0.040) than those in group 0 (0 or 1 RBC-related prognostic factors). Belonging to group 1 independently predicted OS (hazard ratio: 0.65, 95% CI:0.50-0.85; p=0.002) but not PFS (hazard ratio: 0.89, 95% CI: 0.70-1.14, p=0.370) or disease response (OR 0.68, 95% CI: 0.41-1.10; p=0.118) at multivariable analysis.Conclusion: RBC-based group scores independently predicted OS in mRCC patients treated with nivolumab.

Enhancing Prognostication and Treatment Response Evaluation in Primary CNS Lymphoma with 18F-FDG PET/CT.

The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the prognostication and response evaluation of primary central nervous system lymphoma (PCNSL) remains inadequately defined. We conducted a retrospective analysis of 268 consecutive newly diagnosed patients with PCNSL between 2006 and 2020. Of these patients, 105 and 110 patients were included to evaluate the prognostic value of baseline and post-treatment 18F-FDG-PET/CT scans, respectively. Tumor uptake was considered positive when it exceeded that of the contralateral brain upon visual assessment. Quantitative analysis of baseline 18F-FDG-PET/CT included measurement of the maximal standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG). The median age of the 268 patients was 62 years (range: 17-85), with 55% being male. The median progression-free survival (PFS) was 24.5 months (95% confidence interval [CI], 19.9-29.1), and the median overall survival (OS) was 34.5 months (95% CI, 22.9-46.1). The average SUVmax was 15.3 ± 5.7 and the mean TMTV and TLG were 12.6 ± 13.9cm3 and 135.0 ± 152.7g, respectively. Patients with a baseline TMTV ≥17.0cm3 had significantly shorter OS (12.5 vs. 74.0 months, p=0.011). Post-treatment metabolic response by 18F-FDG-PET/CT significantly predicted PFS (median: 10.5 vs. 46.0 months, p=0.001) and OS (median: 21.0 vs. 62.0 months, p=0.002), whereas anatomic response by contrast-enhanced MRI showed no statistically significant differences in PFS (p=0.130) or OS (p=0.540). Baseline TMTV and post-treatment metabolic response, as assessed by 18F-FDG-PET/CT, are significant prognostic factors in patients with PCNSL.

Clinical Outcomes of Enfortumab Vedotin in Advanced Urothelial Carcinoma With Prior Avelumab Versus Pembrolizumab Therapy.

This study retrospectively evaluated whether enfortumab vedotin (EV) monotherapy is effective as a late-line treatment according to prior treatment type in patients with advanced urothelial carcinoma (UC). We assessed consecutive patients from the Uro-Oncology Group in the Kyushu study population with lower and upper urinary tract cancer treated with EV monotherapy after platinum-based chemotherapy and immune checkpoint inhibitor therapy failure between December 2021 and March 2024. In particular, patients receiving avelumab maintenance or pembrolizumab therapy before EV for advanced UC were analyzed and compared according to the response rate, progression-free survival (PFS), and overall survival (OS). Of the 80 enrolled patients, 31 and 49 received avelumab and pembrolizumab before EV therapy, respectively. The avelumab and pembrolizumab groups had comparable objective response rates (48.4% vs. 44.9%, p=0.820) and disease control rates (77.4% vs. 67.3%, p=0.448). These two groups showed no significant difference in PFS from the initiation of EV (median: 6.4 months vs. 4.2 months, p=0.184); meanwhile, the avelumab group had better OS from the initiation of EV than the pembrolizumab group (median: 16.0 months vs. 10.2 months, p=0.019). Moreover, the median OS after first-line chemotherapy initiation was longer in the avelumab group than in the pembrolizumab group (40.3 months vs. 24.7 months, p=0.054). On multivariate analysis, avelumab maintenance therapy before EV reduced the mortality risk by 47% (95% confidence interval=0.27-1.03; p=0.059). EV monotherapy after avelumab maintenance therapy provides favorable survival outcomes in patients with advanced UC.

Enfortumab Vedotin for Elderly Advanced Urothelial Carcinoma Patients or Those With a Poor Performance Status.

The efficacy, safety, and liver toxicity of enfortumab vedotin (EV) for elderly advanced urothelial carcinoma (UC) patients and patients with a poor performance status (PS) are unclear. We retrospectively analyzed the efficacy, safety, and liver toxicity of EV in elderly patients and patients with a poor PS between December 2021 and August 2023. Sixty-two patients (≥75 years old, n=22; PS≥2, n=10) were enrolled. Patients with PS≥2 had significantly lower albumin levels than those with PS<2 (p=0.023). The objective response and disease control rates did not differ significantly between patients <75 and ≥75 years old (p=0.598 and p=0.769, respectively) or between those with PS<2 and PS≥2 (p>0.99 and p=0.178, respectively). Progression-free survival (PFS) and overall survival (OS) were not significantly different in patients <75 years and ≥75 years (p=0984, 0.368). A significant difference in PFS (p=0.047) but not OS (p=0.086) was observed between the PS<2 and PS≥2 groups. The rates of any-grade and severe (grade ≥3) adverse events did not differ significantly between patients <75 and ≥75 years (p=0.471, p=0.136) or between PS<2 and PS≥2 groups (p>0.99, 0.99). Aspartate aminotransferase (AST) levels significantly increased, but alanine aminotransferase levels did not, following EV treatment (p<0.001). Multivariate analyses revealed that the albumin level was an independent prognostic factor (hazard ratio=0.159; p<0.001). EV demonstrated similar efficacy and safety in elderly and younger patients with advanced UC. In patients with a poor PS, although the safety was similar, survival was significantly worse in terms of PFS, while the AST levels were significantly elevated.

Comparison of the Long-term Survival Outcome of Surgery versus Stereotactic Body Radiation Therapy as Initial Local Treatment for Pulmonary Oligometastases from Colorectal Cancer: A Propensity Score Analysis

PurposeOptimal local treatment for pulmonary oligometastases from colorectal cancer (CRC) remains unclear. We aimed to compare the long-term survival outcomes between surgery and stereotactic body radiotherapy (SBRT) as the initial local treatment for CRC pulmonary oligometastases. Materials and MethodsWe retrospectively reviewed 335 consecutive patients who initially underwent surgery or SBRT for CRC pulmonary metastases from 2011 to 2022, and 251 patients (173 surgery and 78 SBRT) were ultimately included. Freedom from intrathoracic progression (FFIP), progression-free survival (PFS), and overall survival (OS) were compared using stabilized inverse probability of treatment weighting (sIPTW) analysis. In addition, patterns of intrathoracic progression and subsequent treatment were analyzed. ResultsMedian follow-up was 61.6 months for surgery and 54.4 months for SBRT. After sIPTW adjustment, significant differences emerged in both FFIP and PFS between surgery and SBRT (FFIP: hazard ratio [HR] = 0.50, 95% confidence interval [CI], 0.31–0.79; PFS: HR = 0.56, 95% CI, 0.36–0.87). The 3- and 5-year FFIP rates were 58.6% and 54.8%, respectively, after surgery, and 34.6% and 31.3%, respectively, after SBRT (P = 0.006). The 3- and 5-year PFS rates were 49.4% and 45.2%, respectively, after surgery, and 28.8% and 26.1%, respectively, after SBRT (P = 0.010). However, OS was not significantly affected by treatment approach (HR = 0.93, 95% CI, 0.49–1.76). The 3- and 5-year OS rates were 85.9% and 73.1%, respectively, after surgery, and 78.9% and 68.7%, respectively, after SBRT (P = 0.849). Recurrence at the treated site was more prevalent after SBRT than after surgery (33.3% vs. 16.9%), whereas new intrathoracic tumors occurred more frequently after surgery than after SBRT (71.8% vs. 43.1%). Both groups chose radiotherapy as the primary local salvage treatment. ConclusionsNotwithstanding the significant differences in FFIP and PFS between surgery and SBRT, the long-term survival of patients with CRC pulmonary oligometastases did not depend on the initial choice of the local treatment approach.

Efficacy of avelumab maintenance therapy for advanced urothelial carcinoma with histologic subtype and divergent differentiation: a multicenter retrospective study conducted by the Uro-Oncology Group in Kyushu.

The subtype of urothelial carcinoma (SUC) has been known to possess morphological diversity for histologic subtype or divergent differentiation. However, the efficacy of avelumab against SUC remains unclear. Therefore, the effect of the treatment as well as the survival results of avelumab monotherapy were evaluated as a first-line therapeutic maintenance in patients with advanced SUC. A retrospective analysis was conducted on consecutive patients from the Uro-Oncology Group in Kyushu study population with advanced lower and upper urinary tract cancer who underwent avelumab maintenance therapy without progression after first-line platinum-based chemotherapy. Patients with pure urothelial carcinoma (PUC) and SUC were comparatively analyzed based on objective response rate (ORR), disease control rate, progression-free survival (PFS), and overall survival (OS). Out of 49 recorded patients, 38 and 11 had PUC and SUC, respectively. The most common subtype element was glandular differentiation (n=5), followed by squamous differentiation (n=3), micropapillary (n=1), and plasmacytoid subtypes (n=1). The SUC and PUC groups had comparable ORR (0% vs. 2.6%, P>0.99) and disease control rates (54.5% vs. 44.7%, P=0.73). These patient groups also showed no significant difference in PFS (median 3.9 vs. 3.1 months, P=0.33) or OS (median 16.7 vs. 22.1 months, P=0.47). The response of SUC and PUC to avelumab was comparable in patients with advanced lower and upper urinary tract cancer, indicating that avelumab maintenance therapy is also effective for SUC.