Significant Difference In Progression-free Survival Research Articles

Comparison of efficacy and safety of PD-1 and PD-L1 antibodies in combination with hepatic arterial infusion chemotherapy and target therapy for unresectable intrahepatic cholangiocarcinoma: A multicenter retrospective study.

553 Background: Immune checkpoint inhibitors (ICIs) in combination with hepatic arterial infusion chemotherapy (HAIC) and target therapy have shown promising antitumor activity in unresectable intrahepatic cholangiocarcinoma (iCCA). The present study aimed to compare the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors in this setting. Methods: In this multicenter retrospective study, we included patients with iCCA who received ICIs + HAIC + target therapy from June 2018 to June 2023. Propensity score matching (PSM) was performed to reduce confounding factors. Patients were divided into two groups: those treated with PD-L1 antibody + HAIC + target therapy (Group A) and those treated with PD-1 antibody + HAIC + target therapy (Group B). Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were compared between the two groups. Adverse events were assessed according to CTCAE v5.0. Results: A total of 336 patients met the inclusion criteria and were enrolled for analysis. There were no significant differences in OS, PFS, or ORR between the two groups (median OS: 17.7 vs. 25.3 months, P=0.139; median PFS: 8.3 vs. 10.0 months, P=0.534; ORR: 48.4% vs. 31.1%, P=0.051). Following PSM (ratio = 3, caliper = 0.2), 30 patients in Group A and 83 patients in Group B were included. The ORR, according to the modified RECIST criteria, was significantly higher in Group A compared to Group B (50% vs. 28.9%, P=0.037). However, no significant difference in PFS (median 10.0 vs. 9.0 months, P=0.29) or OS (median 17.6 vs. 22.8 months, P=0.293) was observed between the two groups. Adverse events (AEs) occurred in all 113 patients (100%), wherein grade 3–4 AEs were reported for 12 (10.6%) patients in group A and 45 (39.8%) in group B. There was a tendency for Group A to have a lower incidence of grade 3–4 AEs compared to Group B (40.0% vs. 54.2%, P=0.182),although this difference was not statistically significant. Conclusions: This study found that in the treatment combining ICIs with HAIC and target therapy for unresectable iCCA, Group A demonstrated a superior tumor response and a more favorable safety profile.

Multicenter, retrospective, observational study of outcomes of treatment for unresectable neuroendocrine tumors G3 of gastroenteropancreatic or unknown primary origin.

660 Background: The 2017 edition of the WHO classification categorized neuroendocrine neoplasms (NEN) as neuroendocrine tumors (NET) G1, G2, G3, and neuroendocrine carcinoma (NEC). Prior to 2017, NET G3 was categorized as NEC in the WHO 2010 classification. Platinum-based chemotherapy, commonly used as first-line treatment for these tumors, shows suboptimal efficacy for NET G3. Additionally, large-scale studies and robust evidence on chemotherapy outcomes for NET G3 are lacking. We investigated chemotherapy regimens for NET G3 and evaluated their outcomes. Methods: We included 73 patients (pts) who were clinically and pathologically diagnosed with unresectable NET G3 of gastroenteropancreatic or unknown primary origin and who started chemotherapy between Jan 2011 and Dec 2019. Clinical data were collected retrospectively and analyzed for regimen selected, treatment efficacy, and prognostic factors. A central pathological review was conducted if tissue samples were available. Results: The median age of pts was 65 years (range 27-85 years), with 45 being male. Among the pts, 49 had pancreatic NETs, 10 had gastrointestinal NETs, and 14 had NETs of unknown primary origin. The median Ki-67 index was 30% (range 20-70%). Twenty-seven patients (37%) had received prior treatment, such as surgery or local therapy. A central pathological diagnosis was confirmed NET G3 in 42 out of 44 patients (95%). Primary treatment regimens were NET-based (somatostatin analogues, everolimus, sunitinib, streptozocin-based chemotherapy, and capecitabine and temozolomide [CAPTEM]) and NEC-based (platinum-based chemotherapy) in 54% and 44% of patients, respectively. NET-based regimens were selected in 36% and 78% of pts, respectively, before and after publication of the WHO 2017 classification. The overall response rate (ORR) was 16% for NEC-based regimens and 19% for NET-based regimens. However, when focusing on NET-based chemotherapy (streptozocin-based and CAPTEM), the ORR was 54%. Median progression-free survival (PFS) was 118 days (95% confidence interval [CI]: 60-337 days) for NET-based regimens and 229 days (95%CI: 133-426 days) for NEC-based regimens. Median overall survival (OS) was 841 days for NET-based regimens (95%CI: 480-989 days) and 658 days (95%CI: 455-1144 days) for NEC-based regimens. There were no significant differences in PFS or OS between the regimens. In multivariable analysis, hepatic tumor volume >25% was a negative predictor of PFS, and NSE ≥16.3 ng/mL was a negative predictor of OS. Conclusions: Since the introduction of NET G3 in the WHO classification, NET-based regimens have become the preferred treatment choice. Although there were no significant differences in PFS or OS between the regimens, the NEC-based regimens was limited. Pts with high hepatic tumor volume or elevated NSE levels had a worse prognosis.

Immunotherapy outcomes in dMMR/MSI-H and/or TMB-H metastatic colorectal cancer (CRC) with peritoneal metastases (PM).

163 Background: CRC with PM has a poor prognosis and limited treatment options. Immunotherapy has shown promise in improving outcomes for patients with microsatellite instability-high (MSI-H), mismatch repair-deficient (dMMR), and high tumor mutational burden (TMB-H) tumors. However the peritoneal niche has a unique microenvironment, which can influence the effectiveness of immune check point inhibitors (ICIs). We assessed the impact of ICI on progression-free survival (PFS) and overall survival (OS) in CRC patients (pts) and PM, considering key clinical and molecular characteristics. Methods: A retrospective review aiming to identify CRC pts with MSI-H/dMMR and PM treated with immunotherapy between 2015 and 2023 was performed. Data collected included pt demographics, tumor characteristics, and treatment details. Responses were evaluated using RECIST v1.1 criteria. Results: 37 pts were included, 9 (24%) had Lynch syndrome. The median age of diagnosis was 61 years and most pts were females (65%). Most pts had MSI-H/dMMR tumors, while one pt was treated based on ultra-hypermutated phenotype (TMB 202) and POLE mutation. Among those with available TMB data, the median TMB was 52 mutations/Mb (0-202). Common mutations were PMS2 (51%), MLH1 (38%), MSH6 (16.2%), and MSH2 (16.2%). Right-sided tumors were in 54%, mucinous histology in 62%, and ascites in 54%. Pts received a median of 11 cycles of ICI (2-52). Pembrolizumab was the most frequently used ICI (78%), while Nivolumab was used either alone (11%) or in combination with Ipilimumab (11%). Median PFS in our cohort was 7.8 months and median OS was 29.9 months. The disease control rate (DCR) was 81%, with an objective response rate (ORR) of 51.3% (9 complete responses, 12 partial responses). At the time of data collection, 30% of pts were off systemic therapy and 5-FU-based chemotherapy combined with a biologic agent was the most common subsequent treatment in 32% who had PD. Univariate analysis showed no significant differences in PFS or OS based on tumor sidedness, isolated PM, liver metastases, mucinous vs. non mucinous histology or BRAF / RAS status (WT vs mutant). Malignant ascites was associated with worse OS(HR 0.3; p= 0.03). Conclusions: Treatment with ICIs in pts with MSI-H/dMMR and/or TMB-H CRC and PM improved disease control in CRC pts with PM, however, as compared to historical controls for patients with MSI-H/d-MMR disease treated with ICI, this group showed less favorable outcomes. Malignant ascites was associated with poorer overall survival. Further research of the immune response and tumor microenvironment in the peritoneal cavity is warranted.

Outcomes and Prognostic Indicators in Daratumumab-Refractory Multiple Myeloma: A Multicenter Real-World Study of Elotuzumab, Pomalidomide, and Dexamethasone in 247 Patients

Daratumumab-refractory multiple myeloma (Dara-R MM) presents a significant treatment challenge. This study aimed to evaluate the efficacy and survival outcomes of elotuzumab, pomalidomide, and dexamethasone (EloPd) in a large, real-world cohort of patients with Dara-R MM, with particular focus on progression-free survival (PFS) and overall survival (OS). This retrospective analysis included 247 Dara-R MM patients treated with EloPd. All patients were also refractory to lenalidomide, with 51.4% to a proteasome inhibitor, thus classified as triple-class refractory (TCR). Survival risk-scoring systems for PFS (progression-free risk score-PRSDaraR) and OS (survival risk score-SRSDaraR) were developed to stratify patients based on their risk profiles. The overall response rate was 52.6%, with a median PFS and OS of 6.6 and 17.0 months, respectively. The International Staging System (ISS) stages II and III, low hemoglobin (Hb) levels, the last therapy being daratumumab, and symptomatic relapse were identified as significant independent predictors of shorter PFS in multivariable analysis. In addition to advanced ISS stages, low Hb levels (<10.6 g/dl), symptomatic relapse, and refractory disease exhibited an independent negative impact on OS. Importantly, no significant differences in both PFS and OS were observed between TCR and non-TCR patients. Based on these multivariable analyses, we developed PRSDaraR and SRSDaraR according to the magnitude of the hazard ratio. In PRSDaraR, 10.1% were low-risk, 41.3% intermediate, 43.3% high, and 5.3% very high-risk. The 12-month PFS probabilities were 86.3% (low), 67.6% (intermediate), 52.9% (high), and 31.8% (very high). For SRSDaraR, 6.1% were low-risk, 47.8% intermediate, 19.4% high, and 26.7% very high. The 12-month OS probabilities were 90.9% (low), 75.7% (intermediate), 55.9% (high), and 32.6% (very high). This study supports EloPd as an effective treatment option in Dara-R MM patients, providing valuable disease control and acting as a potential bridge to newer therapies, such as CAR-T and bispecific antibodies.

Impact of time to surgery on outcomes in patients with advanced esophageal squamous cell carcinoma following neoadjuvant therapy: An exploratory analysis of phase III trial JCOG1109.

458 Background: JCOG1109, a multicenter three-arm phase III trial, evaluated three neoadjuvant treatment regimens for advanced esophageal squamous cell carcinoma (ESCC), cisplatin and 5-fluorouracil (CF), docetaxel, cisplatin, and 5-fluorouracil (DCF), and cisplatin, 5-fluorouracil, and radiation therapy (CF-RT). The trial demonstrated the superiority of neoadjuvant DCF therapy in improving overall survival (OS). This exploratory analysis investigates the impact of the interval time from completion of neoadjuvant therapy to surgery (time to surgery, TTS) on both short- and long-term outcomes across different neoadjuvant therapy regimens. Methods: This analysis included patients from JCOG1109 who underwent surgery after neoadjuvant therapy. Patients were categorized into four TTS subgroups within each arm, based on quartiles of the overall cohort. Short-term outcomes such as perioperative complications, as well as long-term outcomes including OS and progression-free survival (PFS) were evaluated across these TTS subgroups. Results: Of the 601 patients enrolled in JCOG1109, 546 patients proceeded to surgery following neoadjuvant therapy. The median TTS was 35 days (range: 16-81) for the CF arm, 38 days (range: 17-109) for the DCF arm, and 41 days (range: 14-98) for the CF-RT arm. Baseline characteristics were well-balanced across all TTS subgroups in each treatment arm. Short-term outcomes revealed that operative time and overall proportions of postoperative complications were comparable. However, in the CF-RT arm, a longer TTS was associated with increased blood loss (200 ml, 210 ml, 300 ml, 370 ml; p-value for trend test = 0.010) and tended to increase the risk of anastomotic leakage (6%, 7%, 14%, 18%; p-value for trend test = 0.073). No significant differences in OS or PFS were observed across TTS subgroups in any treatment arm, with hazard ratios indicating no clear trend toward improved or worsened long-term outcomes. Conclusions: The timing of surgery following neoadjuvant therapy does not appear to affect long-term prognosis in patients with advanced ESCC, irrespective of the neoadjuvant therapy regimen. However, for patients undergoing neoadjuvant CF-RT, earlier surgery may be advantageous in reducing the risk of increased surgical complexity and anastomotic leakage.

A panel of cancer testis antigens in squamous cell carcinoma of the lung, head and neck, and esophagus: implication for biomarkers and therapeutic targets

This study aims to investigate the expression of seven cancer testis antigens (MAGE-A1, MAGE-A4, MAGE-A10, MAGE-A11, PRAME, NY-ESO-1 and KK-LC-1) in pan squamous cell carcinoma and their prognostic value, thus assessing the potential of these CTAs as immunotherapeutic targets. The protein expression of these CTAs was evaluated by immunohistochemistry in 60 lung squamous cell carcinoma (LUSC), 62 esophageal squamous cell carcinoma (ESCA) and 62 head and neck squamous cell carcinoma (HNSC). The relationship between CTAs expression and progression-free survival (PFS) was assessed. PD-L1 expression and tumor-infiltrating lymphocytes were also collected and correlated with CTAs expression. The prognostic impact of CTAs gene expression was evaluated using the Kaplan–Meier Plotter website. CTAs expression was 0–48% in ESCA, 3%-77% in LUSC, and 3%-71% in HNSC. Analysis of PFS showed that MAGE-A1 expression in HNSC (**p < 0.01), PRAME in LUSC (p = 0.008, **p < 0.01), MAGE-A10 (p = 0.012, *p < 0.05) and PRAME (p = 0.021, *p < 0.05) in ESCA were significantly correlated with PFS. In all three cancers, coexpression of three CTAs was used as a cutoff value for grouping, and the results showed a significant difference in PFS between these two groups. Moreover, CTAs expression was significantly correlated with PD-L1 expression and T cell infiltration. These findings indicate a high incidence of CTA expression in HNSC, LUSC and ESCA, which was correlated with PD-L1 expression, T cell infiltration, and tumor progression. The results suggest that cancer testis antigens could be feasible vaccine targets in squamous cell carcinoma.

Effectiveness of regorafenib in second-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis.

In patients with advanced hepatocellular carcinoma (HCC) following sorafenib failure, regorafenib has been used as an initial second-line drug. It is unclear the real efficacy and safety of sorafenib-regorafenib sequential therapy compared to placebo or other treatment (cabozantinib or nivolumab or placebo) in advanced HCC. Four electronic databases (PubMed, Embase, Web of Science, and Ovid) were systematically searched for eligible articles from their inception to July, 2024. Included articles were selected based on strict eligibility criteria. Review Manager 5.4 software were performed for statistical analysis. Ten studies with 2349 HCC patients of whom 1370 received regorafenib treatment, and 979 underwent cabozantinb, nivolumab or placebo were selected for meta-analysis. The results of our systematic review and meta-analysis found regorafenib could significantly prolong overall survival (standardized mean difference [SMD] = 0.16, 95% CI = 0.02 to 0.29, P = .02) than other treatment (cabozantinib or nivolumab or placebo) in second-line treatment of HCC following sorafenib failure. No significant difference in progression-free survival (SMD = -0.03; 95% CI = -0.13 to 0.06; P = .53), overall response rate (risk ratio [RR] = 0.59; 95% CI = 0.24 to 1.47; P = .26), disease control rate (RR = 1.23; 95% CI = 0.7 to 2.16; P = .48) between 2 groups. Subgroup analysis demonstrated that nivolumab has better overall response rate results than regorafenib (RR = 0.38; 95% CI = 0.24 to 0.61; P < .0001). Compared with other treatment (cabozantinib or nivolumab or placebo), regorafenib seemed to be more effective for patients with HCC who have not responded to initial sorafenib treatment.

3D synergistic tumor-liver analysis further improves the efficacy prediction in hepatocellular carcinoma: a multi-center study

BackgroundBesides tumorous information, synergistic liver parenchyma assessments may provide additional insights into the prognosis of hepatocellular carcinoma (HCC). This study aimed to investigate whether 3D synergistic tumor-liver analysis could improve the prediction accuracy for HCC prognosis.MethodsA total of 422 HCC patients from six centers were included. Datasets were divided into training and external validation datasets. Besides tumor, we also performed automatic 3D assessment of liver parenchyma by extracting morphological and high-dimensional data, respectively. Subsequently, we constructed a tumor model, a tumor-liver model, a clinical model and an integrated model combining information from clinical factors, tumor and liver parenchyma. Their discrimination and calibration were compared to determine the optimal model. Subgroup analysis was conducted to test the robustness, and survival analysis was conducted to identify high- and low-risk populations.ResultsThe tumor-liver model was superior to the tumor model in terms of both discrimination (training dataset: 0.747 vs. 0.722; validation dataset: 0.719 vs. 0.683) and calibration. Moreover, the integrated model was superior to the clinical model and tumor-liver model, particularly in discrimination (training dataset: 0.765 vs. 0.695 vs. 0.747; validation dataset: 0.739 vs. 0.628 vs. 0.719). The AUC of the integrated model was not influenced by AFP level, BCLC stage, Child–Pugh grade, and treatment style in training (6 months p value: 0.245–0.452; 12 months p value: 0.357–0.845) and validation (6 months p value: 0.294–0.638; 12 months p value: 0.365–0.937) datasets. With a risk score of 1.06, high- and low-risk populations demonstrated significant difference for progression-free survival (p < 0.001 in both datasets).ConclusionsCombined with clinical factors, 3D synergistic tumor-liver assessment improved the efficacy prediction of HCC.

Pembrolizumab ± paricalcitol in metastatic pancreatic cancer postmaximal cytoreduction.

Intravenous paricalcitol did not improve the efficacy of pembrolizumab, likely related to the short half-life. Immunotherapy has limited benefit in the treatment of advanced pancreatic cancer with the tumor microenvironment playing a key role in immune resistance. In preclinical studies, vitamin D receptor (VDR) agonists have been shown to sensitize pancreatic tumors to PD-1 blockade. This was a randomized, double-blinded, placebo-controlled, phase II trial to evaluate pembrolizumab with or without paricalcitol as maintenance therapy for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Participants were ≥18 years; histologically or cytologically confirmed metastatic PDAC showing no disease progression after frontline systemic therapy, and achieving maximal cytoreduction (eg, with no further antitumor effect), Eastern Cooperative Oncology Group (ECOG) status of 0 or 1; adequate organ function. Study treatment included: pembrolizumab 200mg IV every 3 weeks and either paricalcitol 25 mcg IV 3 times per week or placebo. The primary objective was to evaluate 6-month progression free survival (PFS). Secondary objectives include evaluating the toxicity of the combination and overall survival (OS). There was no significant difference in 6-month PFS, median PFS, median OS, nor treatment-related AEs between the 2 arms. Paricalcitol did not improve the efficacy of pembrolizumab likely related to its short half-life of only 5-7 hours. Microbiome analysis revealed significant difference between long-term (>12 weeks) and short-term (<12 weeks) survival groups across treatment arms. Modulation of the tumor microenvironment will likely require more sustained VDR activity. Clinicaltrials.gov, ID: NCT03331562.

Salvage Autologous Transplant in Relapsed Multiple Myeloma: Long-Term Follow-Up of the Phase 3 GMMG ReLApsE Trial.

The multicenter, phase III GMMG ReLApsE trial (EudraCT-No:2009-013856-61) randomized relapsed and/or refractory multiple myeloma (RRMM) patients equally to lenalidomide/dexamethasone (LEN/DEX, 25mg days 1-21/40mg weekly, 4-week cycles) re-induction, salvage high dose chemotherapy (sHDCT, melphalan 200mg/m2), autologous stem cell transplantation (ASCT) and LEN maintenance (10mg/day; transplant arm, n=139) versus continuous LEN/DEX (control arm, n=138). Ninety-four percent of patients had received frontline HDCT/ASCT. We report an updated analysis of survival endpoints with a median follow-up of 99 months. Median progression-free survival (PFS) was 20.5 and 19.3 months in the transplant and control arm, respectively (HR 0.98; 95% CI 0.76-1.27; p=0.9). Median overall survival (OS) was 67.1 and 62.7 months (HR 0.89; 95% CI 0.66-1.20; p=0.44). Landmark analyses from sHDCT and the contemporaneous LEN/DEX cycle 5 were performed due to dropout of 29% of patients before sHDCT/ASCT in the transplant arm but did not reveal significant differences in PFS (23.0 vs. 20.3 months; HR 0.91; 95% CI 0.68-1.22; p=0.52) or OS (76.3 vs. 66.0 months; HR 0.8; 95% CI 0.56-1.13; p=0.2). Time to progression after frontline HDCT/ASCT (TTP1) was a prognostic factor but did not predict benefit from sHDCT/ASCT. The GMMG ReLApsE trial does not support use of sHDCT/ASCT in RRMM after frontline HDCT/ASCT. EudraCT-No: 2009-013856-61.

Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation Versus Adjuvant Chemotherapy Following Concurrent Chemoradiation for Locally Advanced Cervical Cancer: A Network Meta-Analysis.

Neoadjuvant chemotherapy followed by concurrent chemoradiation therapy (NACT + CCRT) and adjuvant chemotherapy following CCRT (CCRT + ACT) have inconsistent effects on the survival of women with locally advanced cervical cancer (LACC) compared to CCRT. Moreover, the effects of NACT + CCRT and CCRT + ACT have not been clearly compared. This study compared the effects of NACT + CCRT and CCRT + ACT on survival using a network meta-analysis to select the optimal treatment in women with LACC. The PubMed, Medline, and Embase databases were searched, and six randomized controlled trials assessing the progression-free survival (PFS) and overall survival (OS) in women with newly diagnosed LACC treated with NACT + CCRT, CCRT + ACT, or CCRT alone (controls) were identified. A network meta-analysis was conducted. Indirect comparisons showed no significant differences in PFS and OS between NACT + CCRT and CCRT + ACT. Direct comparisons also showed similar PFS and OS between NACT + CCRT and CCRT and between CCRT + ACT and CCRT. CCRT + ACT exhibited the highest surface under the cumulative ranking curve (SUCRA) value as a better treatment option for the PFS and OS (CCRT + ACT vs. NACT + CCRT vs. CCRT: 72% vs. 26.8% vs. 51.2% in PFS and 64.3% vs. 45.1% vs. 40.7% in OS). In women with LACC, NACT + CCRT had no different effects on the PFS and OS compared to CCRT + ACT, despite the relatively higher SUCRA value observed for CCRT + ACT. Further studies are warranted to clarify the effects of these strategies.

The Potential Role of sPD-L1 as a Predictive Biomarker in EGFR-Positive Non-Small-Cell Lung Cancer.

A significant breakthrough in non-small-cell lung cancer (NSCLC) treatment has occurred with the introduction of targeted therapies and immunotherapy. However, not all patients treated with these therapies would respond to treatment, and patients who respond to treatment would acquire resistance at some time point. This is why we need new biomarkers that can predict response to therapy. The aim of this study was to investigate whether soluble programmed cell death-ligand 1 (sPD-L1) could be a predictive biomarker in patients with epidermal growth factor receptor (EGFR)-positive NSCLC. Blood samples from 35 patients with EGFR-mutated (EGFRmut) adenocarcinoma who achieved disease control with EGFR tyrosine kinase inhibitor (EGFR TKI) therapy were collected for sPD-L1 analysis. We analyzed sPD-L1 concentrations in 30 healthy middle-aged subjects, as a control population, to determine the reference range. Adenocarcinoma patients were divided into two groups, i.e., a group with low sPD-L1 (≤182.5 ng/L) and a group with high sPD-L1 (>182.5 ng/L). We found that progression-free survival (PFS) was 18 months, 95% CI (11.1-24.9), for patients with low sPD-L1 and 25 months, 95% CI (8.3-41.7), for patients with high sPD-L1. There was no statistically significant difference in PFS between the groups (p = 0.100). Overall survival (OS) was 34.4 months, 95% CI (26.6-42.2), for patients with low sPD-L1 and 84.1 months, 95% CI (50.6-117.6), for patients with high sPD-L1; there was also no statistically significant difference between the groups (p = 0.114). In our study, we found that patients with high sPD-L1 had numerically better PFS and OS, but this has no statistical significance. Further studies with a larger number of patients are needed to evaluate the role of sPD-L1 as a predictive biomarker in patients with EGFRmut NSCLC.

The real-world efficacy and safety of frontline therapy of obinutuzumab plus bendamustine for untreated high-tumor-burden follicular lymphoma.

While R-CHOP has been one of the standard therapies for untreated high-tumor-burden (HTB) follicular lymphoma (FL) for over 2 decades, obinutuzumab plus bendamustine (OB) is also currently regarded as the standard of care since its approval in 2018 in Japan; however, the long-term efficacy and safety of OB in the daily clinical practice has not been thoroughly evaluated. We conducted a multicenter retrospective study for the clinical outcome of 53 patients with HTB FL treated by OB as the frontline therapy between 2018 and 2021 in the Kyoto Hematology Clinical Study Group (KOTOSG). All patients had at least 2-year follow-up period. The median age was 67, and 60.4% were classified as high risk according to the Follicular Lymphoma International Prognostic Index. The overall and complete response rates after induction therapy with OB were 98% and 83%, respectively. With a median follow-up of 38.5months, the 3-year progression-free survival (PFS) and overall survival (OS) were 77.3% and 91.2%, respectively. Grade 3-4 hematological adverse events (AEs) were common, including neutropenia (58.5%) and lymphopenia (98.1%). Non-hematological AEs included infections, such as lung infections, coronavirus disease 2019, and sepsis, with two cases (3.8%) being fatal. Finally, propensity score-matched analysis showed no significant difference in PFS between 46 FL patients treated by the frontline OB and 46 FL patients treated by R-CHOP between 2001 and 2019 in KOTOSG. This study highlighted the need for careful treatment selection based on patient background and disease condition in real-world practice with more elderly patients.

Immune Checkpoint Inhibitors +/- Chemotherapy for Patients With NSCLC and Brain Metastases: A Systematic Review and Network Meta-Analysis.

Multiple studies have demonstrated the intracranial efficacy of immune checkpoint inhibitors (ICI) +/- chemotherapy. The efficacy of chemoimmunotherapy compared to ICI alonein patients with metastatic NSCLC and brain metastases (BM) remains unknown. A systematic review and network meta-analysis were performed to evaluate ICI efficacy and the influence of additional chemotherapy on survival outcomes in treatment-naïve metastatic NSCLC with BM. Randomized phase II/III studies with at least one treatment arm with an ICI were eligible. Overall survival (OS) and progression-free survival (PFS) in patients with and without BM were assessed. Ten studies were included, totaling 6560 patients, 770 with BM. Pairwise meta-analysis revealed that patients with BM treated with ICI +/- chemotherapy had improved PFS (hazard ratio [HR] 0.49; 95% CI 0.40-0.60) and OS (HR 0.55; 95% CI 0.44-0.68) versus chemotherapy alone. Patients without BM treated with ICI +/- chemotherapy also had improved PFS and OS compared to chemotherapy alone. In the network meta-analysis of patients with BM, chemoimmunotherapy demonstrated improved PFS compared to ICI alone (HR 0.64; 95% CI 0.43-0.96; p = 0.03). No significant difference was observed in OS. In the population of patients without BM, no significant differences in PFS or OS were observed between chemoimmunotherapy versus ICI alone. This meta-analysis confirms that ICIs with or without chemotherapy are superior to chemotherapy alone for the first-line management of metastatic NSCLC with and without BM. This network meta-analysis suggests combination chemoimmunotherapy offers PFS benefit over ICI monotherapy in BM patients, warranting direct comparisons in clinical trials. PROSPERO: CRD42024501345.

Polo-like Kinase 1 Expression as a Biomarker in Colorectal Cancer: A Retrospective Two-Center Study.

Background/Objectives: Early-onset colorectal cancer (EOCRC) is more frequently characterized by poorly differentiated, aggressive tumors, often diagnosed at advanced stages, and associated with worse prognoses. Despite these differences, current treatment guidelines do not distinguish between EOCRC and late-onset colorectal cancer (LOCRC). Elevated expression of polo-like kinase 1 (PLK-1) has been linked to advanced disease stages and poorer treatment outcomes, including resistance to both chemotherapy and radiotherapy. However, data on PLK-1 expression in EOCRC compared to LOCRC remain limited. Methods: Patients with sporadic CRC, aged >18 years, were included in this study. We categorized the patients into two groups: patients younger than 50 years, and those aged 50 years or older. Immunohistochemical staining was performed to assess PLK-1 expression. The aim of this study was to assess PLK-1 expression considering the age of the patients and its effects on overall survival (OS) and progression-free survival (PFS). Results: A total of 146 patients with metastatic colorectal cancer (mCRC) were included in this retrospective two-center study. Patients with low PLK-1 expression were older than patients with high PLK-1 expression (64 (49-71) years vs. 49 (42-67) years, p = 0.016). Multiple logistic regression confirmed that age is a significant predictor of PLK-1 expression, independent of the covariates (p = 0.036). The Kaplan-Meier analysis revealed no significant association between PLK-1 expression and PFS (p = 0.397) or OS (p = 0.448). Accordingly, Cox proportional hazards regression analysis showed no significant association between PLK-1 expression and OS (HR 1.20, 95% CI 0.73-1.96, p = 0.598) or PFS (HR 0.85, 95% CI 0.51-1.43, p = 0.611) when covariates were taken into account. Finally, no significant differences in PFS (p = 0.423) or OS (p = 0.104) were found between the age groups of interest. Conclusions: PLK-1 expression was not associated with survival or progression in EOCRC and LOCRC patients. Further research on these combinations is necessary, as well as the discovery of new potential targets for targeted therapy and the mechanisms of synergistic effects in tumors with PLK-1 overexpression.

Rapid and Deep Prostate-Specific Antigen Decline is a Prognostic Marker in Metastatic Hormone-Sensitive Prostate Cancer: A Real-World Multi-Intuitional Analysis.

Prostate-specific antigen (PSA) kinetics has been investigated as a prognostic marker in post hoc analyses of clinical trials. This study validated the prognostic value of rapid and deep PSA decline in metastatic hormone-sensitive prostate cancer (mHSPC) using real-world data. In total, 1296 patients with mHSPC were retrospectively reviewed. We assessed the prognostic value of a PSA decline to ≤ 0.2 ng/mL after 12 weeks of treatment and investigated several potential risk factors for a poor PSA response. Of 1296 patients, 714 (cohort 1: 55.1%) were treated with conventional hormonal therapy, while 582 (cohort 2: 44.9%) received androgen signaling inhibitors. There were significant differences in progression-free survival and overall survival between patients with PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment and others (p < 0.001 for each). In addition, patients with an initial PSA ≥ 200 ng/mL, Clinical T4 and Grade Group 5 were less likely to achieve PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment, with odds ratios of 0.31 (p < 0.001), 0.67 (p = 0.039) and 0.70 (p = 0.043), respectively. Our findings suggested that PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment may be a useful prognostic biomarker for mHSPC in the real-world setting. The prognostic value of this should be further investigated in a prospective cohort, and identification of an optimal cutoff value is necessary for its application in clinical trial design or clinical practice.

Prognostic value of interim PET/CT in GCB and non-GCB DLBCL: comparison of the Deauville five-point scale and the ΔSUVmax method

BackgroundThis study aimed to identify the prognostic value of interim 18F-FDG PET/CT (I-PET) for germinal center B-cell-like (GCB) and non-GCB diffuse large B-cell lymphoma (DLBCL), respectively.MethodsBaseline 18F-FDG PET/CT (B-PET) and I-PET scans were performed in 112 patients with DLBCL. The prognostic value of I-PET using the Deauville five-point scale (D-5PS) criteria or percentage decrease in SUVmax (∆SUVmax) for GCB and non-GCB DLBCL were evaluated.ResultsA significant difference in progression-free survival (PFS) was found between GCB and non-GCB DLBCL patients (P < 0.05). Based on D-5PS criteria, I-PET was divided into positive (score > 3) and negative (score ≤ 3) subgroups. Results indicated that I-PET using D-5PS criteria was an independent predictor for PFS of GCB DLBCL (P < 0.05), but not for overall survival (OS) (P > 0.05). For non-GCB DLBCL, PFS and OS were significantly higher in I-PET negative group than I-PET positive group (P < 0.05). Receiver operating characteristic (ROC) curve analysis proved that I-PET using ΔSUVmax can also effectively predict PFS and OS of non-GCB DLBCL (P < 0.05), but not for GCB DLBCL (P > 0.05). Based on the optimal threshold found by ROC curve analysis, patients were dichotomized into ∆SUVmax high and low groups. Log-rank test and Cox regression demonstrated that the layered ∆SUVmax was predictive of PFS and OS in non-GCB DLBCL (P < 0.05).ConclusionsI-PET may have different prognostic values for GCB and non-GCB DLBCL. Thus, the pathology type of DLBCL may be considered while using I-PET as a prognostic tool in the future.

Trends in Real-World Clinical Outcomes of Patients with Anaplastic Lymphoma Kinase (ALK) Rearranged Non-Small Cell Lung Cancer (NSCLC) Receiving One or More ALK Tyrosine Kinase Inhibitors (TKIs): A Cohort Study in Ontario, Canada.

The treatment landscape for patients with advanced ALK-positive NSCLC has rapidly evolved following the approval of several ALK TKIs in Canada. However, public funding of ALK TKIs is mostly limited to the first line treatment setting. Using linked provincial health administrative databases, we examined real-world outcomes of patients with advanced ALK-positive NSCLC receiving ALK TKIs in Ontario between 1 January 2012 and 31 December 2021. Demographic, clinical characteristics and treatment patterns were summarized using descriptive statistics. Kaplan-Meier analysis was performed to evaluate progression-free survival (PFS) and overall survival (OS) among the treatment groups. A total of 413 patients were identified. Patients were administered alectinib (n = 154), crizotinib (n = 80), or palliative-intent chemotherapy (n = 55) in the first-line treatment. There was a significant difference in first-line PFS between the treatment groups. The median PFS (mPFS) was not reached for alectinib (95% CI, 568 days-not reached), compared to 8.2 months (95% CI, 171-294 days) for crizotinib (HR = 0.34, p < 0.0001) and 2.4 months (95% CI, 65-100 days) for chemotherapy (HR = 0.14, p < 0.0001). There was no significant difference in first-line OS between the treatment groups. In patients who received more than one line of treatment, there was a significant difference in mOS between patients who received two or more lines of ALK TKIs compared to those who received one line of ALK TKI (mOS = 55 months (95% CI, 400-987 days) and 26 months (95% CI, 1448-2644 days), respectively, HR = 4.64, p < 0.0001). This study confirms the effectiveness of ALK TKIs in real-world practice and supports the potential benefit of multiple lines of ALK TKI on overall survival in patients with ALK-positive NSCLC.

Clinical characteristics and survival outcomes in patients with pulmonary sarcomatoid carcinoma: a multicenter retrospective study

Abstract Purpose The clinicopathologic features, mutational status, immunohistochemical markers, and prognosis of Pulmonary sarcomatoid carcinoma (PSC) remain uncertain. Methods This study included 81 PSC and 337 lung adenocarcinomas (LUAD). Progression-free survival (PFS), overall survival (OS), and other clinical data were examined. Results 46% PSC patients harbored KRAS mutation and 23% harbored EGFR mutation. Univariable analysis identified type and cTNM stage as significant predictor of PFS (type: HR 0.216; 95% CI 0.133–0.349; P &lt; 0.001, cTNM stage: HR 0.483; 95% CI 0.269–0.846; P = 0.014) and OS (type: HR 0.269; 95% CI 0.156–0.465; P &lt; 0.001, cTNM stage: HR 0.435; 95% CI 0.219–0.865; P = 0.018). Multivariable analysis confirmed sex, type and cTNM stage as independent predictors of PFS (sex: HR 2.026; 95%CI 1.027–3.996; P = 0.042; type: HR0.140; 95% CI 0.083–0.238; P &lt; 0.001, cTNM stage: HR0.305; 95% CI 0.165–0.564; P &lt; 0.001) and OS (type: HR0.231; 95% CI 0.132–0.404; P &lt; 0.001, cTNM stage: HR 0.394; 95% CI 0.194–0.797; P = 0.010). Significant differences in PFS (P &lt; 0.0001) and OS (P = 0.022) were observed between PSC and LUAD, and for PC compared with SCC (PFS: P = 0.00036, OS: P = 0.0053). Additionally, PSC patients treated with immunotherapy showed significantly better OS (P = 0.0019) compared with those treated without immunotherapy. Conclusions PSC exhibits high KRAS and EGFR mutation rates, and spindle cell carcinoma has a worse prognosis. Immunotherapy shows potential as a treatment for advanced PSC.

Efficacy and safety of antibody-drug conjugates in pretreated HER2-low metastatic breast cancer: A systematic review and network meta-analysis.

Antibody-drug conjugates (ADCs) trastuzumab-deruxtecan (T-DXd) and sacituzumab-govitecan (SG) provided significant progression-free survival (PFS) and overall survival (OS) improvements over chemotherapy (CT) in pretreated hormone receptor-positive (HR+) and triple-negative (TN)/HER2-low metastatic breast cancer (MBC). However, no direct comparison between the two exists, nor with the more recent datopotamab-deruxtecan (Dato-DXd). We conducted a network meta-analysis (NMA) to compare efficacy and safety of T-DXd and SG in CT-pretreated HR+and TN/HER2-low MBC and assess their benefit over standard CT, exploring also a comparison with Dato-DXd. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for PFS/OS. P-score was used for treatment ranking. Three RCTs (956 patients) were included in the primary analysis and 5 (1,445) in the exploratory NMA with Dato-DXd. In HR+/HER2-low, T-DXd showed no significant difference in PFS and OS when compared to SG. Similarly, in TN/HER2-low, PFS and OS did not differ significantly between the two ADCs. The P-score analysis favored T-DXd over SG in HR+/HER2-low in PFS (0.90 vs. 0.60) and OS (0.89 vs. 0.60). SG was favored over T-DXd in OS in TN/HER2-low (0.80 vs. 0.69). Similar results were obtained for HR+MBC when including Dato-Dxd, which showed the worst performance, while T-DXd was the only ADC significantly outperforming CT in OS. The ADCs showed significantly better PFS and OS than CT in HR+/HER2-low and TN/HER2-low (all p<0.001). SG had higher rates of neutropenia, diarrhea and alopecia vs. T-DXd, which showed more thrombocytopenia, fatigue and nausea. Pneumonitis and cardiotoxicity were typically T-DXd-related, and T-DXd showed more toxicity-related discontinuations. Similar efficacy with T-DXd and SG in HER2-low MBC was observed, regardless of HR status. Safety profile, local drug-approval criteria and guidelines, patients' preferences and overall quality of evidence should ultimately guide therapeutic decision-making. Dato-DXd role remains uncertain.