Prognostic impact of oligometastasis in older patients with extensive-stage small cell lung cancer.

Immune checkpoint inhibitors (ICIs) combined with etoposide-platinum are recommended as the standard first-line therapy for extensive-stage small cell lung cancer (ES-SCLC). Despite the potential of antiangiogenic agents to enhance treatment efficacy, the optimal combination pattern remains unclear. This meta-analysis explores existing treatment strategies involving ICIs or antiangiogenic agents in ES-SCLC. Hazard ratios (HRs) and odds ratios (ORs) were generated by R software. The outcomes of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events of grade 3 or higher (Grade ≥3 AEs) were analyzed. The included trials were classified in terms of different treatment strategies, including ICI + Chemotherapy (ICI + Chemo), ICI + ICI + Chemotherapy (ICI + ICI + Chemo), ICI + Antiangiogenic agent + Chemotherapy (ICI + Antiangio + Chemo), Antiangiogenic agent + Chemotherapy (Antiangio + Chemo), and Chemotherapy (Chemo). A total of 13 randomized controlled trials (RCTs) involving 6,822 patients were included in the analysis. The drug combination patterns included ipilimumab, durvalumab, adebrelimab, atezolizumab, socazolimab, pembrolizumab, serplulimab, tislelizumab, toripalimab, durvalumab + tremelimumab, tiragolumab + atezolizumab, benmelstobart + anlotinib, bevacizumab + atezolizumab, anlotinib, bevacizumab in combination with chemotherapy. The antiangiogenic agent-containing regimen benmelstobart + anlotinib + chemotherapy demonstrated the highest potential to achieve superior PFS and OS versus chemotherapy. The group meta-analysis also showed that ICI + Chemo, ICI + ICI + Chemo, and ICI + Antiangio + Chemo presented significantly better OS. Additionally, ICI + Antiangio + Chemo achieved better PFS with the lowest HR of 0.37 and the best ORR of 2.08 versus chemotherapy. Patients treated with benmelstobart + anlotinib + chemotherapy, durvalumab + tremelimumab + chemotherapy, and anlotinib + chemotherapy experienced a higher likelihood of grade ≥3 AEs. For individuals with ES-SCLC, ICI + Antiangio + Chemo was identified as an optimal treatment option due to better OS, PFS, and ORR. Benmelstobart + anlotinib + chemotherapy demonstrated a better survival benefit than chemotherapy. The toxicity of ICI + Antiangio + Chemo was acceptable but needed careful attention. These findings clarified the roles of ICIs and antiangiogenic agent-based treatment strategies in this population.

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Elderly Patients: Expert Review

9012 Background: Immune checkpoint inhibitor (ICI) plus chemotherapy is now a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alternations. However, the efficacy and safety of ICI plus chemotherapy (ICI-chemo) in 75 years or older patients have not been elucidated. The aim of this study is to reveal the real-world choice of first-line drugs in elderly patients (pts) and evaluate the efficacy and safety of ICI-chemo. Methods: We conducted a multicenter (58 centers in Japan), retrospective cohort study of consecutive 75 years or older pts with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC who started first-line systemic therapy between December 2018 and March 2021. Pts with epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or whose first-line systemic therapy was molecular targeted therapy were excluded. Results: A total of 1245 pts were enrolled: median (range) age 78 (75-95) years; 278 (22%) female; 367 (29%) ECOG PS 0, 680 (55%) PS 1 and 171 (14%) PS 2; 678 (54%) adenocarcinoma; PD-L1 tumor proportion score 268 (22%) <1%, 387 (31%) 1-49% and 410 (34%) ≥50%; 354 (28%) ICI-chemo, 425 (34%) ICI alone, 311 (25%) platinum-doublet chemotherapy and 155 (12%) single agent chemotherapy. The median overall survival (OS) was 20.0 months (95%CI, 17.1–23.6) in the ICI-chemo group, 19.8 months (95%CI, 16.5–23.8) in the ICI alone group, 12.8 months (95%CI, 10.7–15.6) in the platinum-doublet chemotherapy group and 9.5 months (95%CI, 7.4–13.4) in the single agent chemotherapy group, respectively. After propensity score matching, there was no difference in OS and progression-free survival (PFS) between ICI-chemo group (n=96) and ICI alone group (n=95) in PD-L1 ≥1% (OS: HR, 0.98; 95% CI, 0.67-1.42, PFS: HR, 0.92; 95% CI, 0.67-1.25). Regardless of PD-L1 subgroups (1-49% or ≥50%), no significant differences in OS and PFS were observed. Concerning safety, Grade 3 or higher immune-related adverse events (irAEs) occurred in 86 pts (24.3%) in the ICI-chemo group and 76 pts (17.9%) in the ICI alone group (p = 0.03). The number of pts who required steroids for irAEs was 115 (32.5%) in the ICI-chemo group and 105 (24.7%) in the ICI alone group (p = 0.02). Pneumonitis was reported in 83 pts (23.4%) in the ICI-chemo group and 66 pts (15.6%) in the ICI alone group (p = 0.006). Conclusions: In real-world data for pts aged 75 years or older, ICI-chemo did not improve survival and increased the incidence of grade 3 or higher irAEs compared to ICI alone. Based on our results, ICI alone is recommended for elderly pts with PD-L1 positive NSCLC. Clinical trial information: UMIN000046700 .

e16166 Background: Hepatocellular carcinoma (HCC) remains a significant global health challenge While immune checkpoint inhibitors (ICIs) have become standard first-line treatments, identifying effective second-line therapies remains an unmet need. This study evaluates the efficacy and safety of regorafenib as a second-line option in advanced HCC patients post-progression on ICI-based regimens. Methods: This retrospective study included advanced HCC patients from eight hospitals in China who received regorafenib after progression on first-line ICI therapies, alone or combined with ICIs. Propensity score matching (PSM) was used to ensure comparability between treatment groups. The primary endpoint was overall survival (OS), secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). Results: A total of 149 patients were included: 113 in the combination therapy group (Rego-ICI group) and 36 in the regorafenib monotherapy group (Rego group). After PSM, there were 67 patients in the Rego-ICI group and 31 in the Rego group. The median age was 59.00 years. Most patients had HBV-related infection (83.9%), ECOG PS 1 (76.3%), and Child-Pugh class A (73.2%). In the first-line treatment, only 10.7% of patients received ICI combined with bevacizumab, the rest were combined with MKIs. After PSM, there were 67 patients in the Rego-ICI group and 31 in the Rego group. The Rego-ICI group showed significantly improved median PFS (4.0 vs. 3.0 months, HR : 0.62 [95% CI: 0.389-0.986]) and OS (19.0 vs. 11.0 months, HR = 0.475 [95% CI: 0.272-0.832]) compared to the Rego group. Differences in ORR and DCR were not statistically significant (ORR 19.4% vs. 9.7%, P = 0.226; DCR 64.2% vs. 48.4%, P = 0.139), but the Rego-ICI group showed better disease control. Multivariate Cox analysis identified regorafenib plus ICI treatment as a protective factor for both PFS and OS. Subgroup analysis showed OS improvement with Rego-ICI in older patients ( > 60 years), ECOG 1/2, BCLC C stage, AFP < 400 ng/mL, and those with vascular invasion and/or extrahepatic metastasis. PFS improvement with Rego-ICI was observed in subgroups with ECOG 1/2, ALBI 2/3, NLR < 3.64, and PLR ≥ 136.9. In the Rego-ICI group, patients with NLR < 3.64 had significantly longer OS than those with NLR ≥ 3.64 (20.0 months vs. 16.8 months, P = 0.036). Conclusions: Adding ICIs to regorafenib therapy significantly improves OS in advanced HCC patients post-progression on first-line ICI treatments, highlighting the potential of regorafenib plus ICIs as an effective second-line option. These findings provide a strong foundation for further prospective clinical research. Clinical trial information: ChiCTR2400091318 .

Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: A systematic review and meta-analysis.

Extensive-stage small cell lung cancer (ES-SCLC) is a highly aggressive subtype of lung cancer with limited treatment options and poor prognosis. In recent years, immune checkpoint inhibitors (ICIs) combined with chemotherapy have demonstrated significant efficacy in several clinical trials. This study aims to evaluate the efficacy of first-line chemotherapy combined with immunotherapy in patients with ES-SCLC and identify prognostic factors based on real-world data. This retrospective study analyzed the clinical data of 349 patients with ES-SCLC treated at Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2018 to August 2023. The patients were divided into a combination group (chemotherapy plus immunotherapy, n = 173) and a chemotherapy group (chemotherapy alone, n = 176) based on their treatment regimens. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was treatment-related adverse events. Kaplan–Meier survival analysis was performed, and Cox regression models were used to analyze the factors influencing OS and PFS. The median OS in the combination group was 14.9 months, significantly longer than 11.9 months in the chemotherapy group (P < 0.001). After applying Propensity Score Matching (PSM) to minimize selection bias, the survival advantage remained statistically significant. The 1-, 2-, and 3-year OS rates in the combination group were 62.4%, 42.8%, and 19.5%, respectively, compared to 50.2%, 20.8%, and 9.6% in the chemotherapy group. The median PFS in the combination group was 5.4 months, also significantly longer than the 3.8 months observed in the chemotherapy group (P < 0.001). Multivariate analysis identified chemotherapy alone, ECOG performance status, and number of metastatic sites as independent risk factors for poorer OS and PFS (P < 0.001). A separate analysis was conducted to evaluate the association between tumor response (CR/PR/SD/PD) and survival outcomes, which showed that patients with CR/PR had significantly better OS and PFS compared to those with SD/PD (P < 0.001). These findings reinforce the clinical importance of achieving tumor response. There were no significant differences in the incidence of adverse events between the two groups, with most adverse events being grade 1–2, and no grade 5 adverse events were reported. This study demonstrates that chemotherapy combined with immunotherapy significantly prolongs OS and PFS in patients with ES-SCLC without substantially increasing treatment-related adverse events. This combination therapy shows promising clinical value for improving long-term prognosis in ES-SCLC patients. Future studies should explore potential biomarkers to optimize individualized treatment strategies.

Given the limited evidence on prognostic factors specifically for older patients with extensive-stage small cell lung cancer (ES-SCLC), a population with distinct clinical characteristics, this study aimed to validate whether previously reported prognostic indicators retain their predictive value in this vulnerable group. A retrospective analysis was conducted on data from 270 older ES-SCLC patients who received treatment at the Fourth Hospital of Hebei Medical University between December 2016 and June 2024. By the final follow-up date of October 15, 2024, 212 deaths had been recorded. The median progression-free survival (mPFS) was 6.7 months (95% confidence interval [CI] 6.0-7.4), and the median overall survival (mOS) was 13.1 months (95% CI 11.8-14.4). For PFS, univariate and multivariate Cox analyses identified first-line chemotherapy (CT) and old-old (≥ 75 years) as independent adverse prognostic factors. For OS, old-old, a positive smoking history, bone metastasis, and high-lactate dehydrogenase (> 250 U/L) were identified as significant adverse prognostic factors. Notably, high-pro-gastrin-releasing peptide (ProGRP) (> 69.2 pg/mL) was significantly associated with an increased risk of death during the follow-up period beyond 10 months (HR = 1.85, 95% CI 1.05-3.26, p = 0.032); conversely, no significant association was observed within the initial 10 months of follow-up (HR = 0.84, 95% CI 0.44-1.60, p = 0.604). In conclusion, these findings not only corroborate the prognostic value of previously identified risk factors in older patients with ES-SCLC but also demonstrate that the prognostic impact of ProGRP is distinctly time-dependent.

Background: Immunotherapy in combination with platinum-etoposide (EP) chemotherapy has been approved as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, real-world (RW) data regarding the use of immune checkpoint inhibitors (ICIs) in ES-SCLC are lacking. We aimed to assess the differences between programmed death protein 1 (PD-1) inhibitors and programmed death ligand 1 (PD-L1) inhibitors, both in conjunction with EP chemotherapy, as first-line treatment for ES SCLC. Methods: We conducted a real-world, multicenter, retrospective cohort, controlled study to compare the prognosis, efficacy, and safety of PD-1 and PD-L1 inhibitors in ES-SCLC patients when used along with chemotherapy. Each patient received up to six cycles of etoposide, carboplatin, or cisplatin combined with ICI drugs, including PD-1 and PD-L1 inhibitors. The primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were the investigator-assessed objective response rate (ORR) and disease control rate (DCR) according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results: Between January 2017 and December 2021, 194 patients with ES-SCLC from three clinical centers in a PLA general hospital were included in our study, including 93 patients in the PD-1 group and 101 patients in the PD-L1 group. At the time of data cutoff, progression-free survival in the PD-1 group (median PFS, 6.8 months; 95% CI, 5.3–8.1 was similar to that in the PD-L1 group (median PFS, 6.4 months; 95% CI, 5.5–7.5); the stratified hazard ratio for PFS was 1.12 (95% CI, 0.83–1.53; P = 0.452). The median OS was similar in the PD-1 and PD-L1 groups (15.8 m vs. 17.7 m, P = 0.566); the hazard ratio was 0.90 (95% CI, 0.62–1.30, P = 0.566). The two groups had comparable investigator-assessed confirmed objective response rates (ORR) (76.3% vs. 76.2%). Adverse effect (AE)-related discontinuation occurred in 4 (4.3%) patients in the PD-1 group and 2 (2.0%) patients in the PD-L1 group. Deaths due to AEs of any cause occurred in 2 (2.2%) patients in the PD-1 inhibitor group and 1 (1.0%) patient in the PD-L1 inhibitor group.

Outcomes of Consolidative Thoracic Radiation within First-Line Chemoimmunotherapy in Extensive-Stage Small-Cell Lung Cancer: Results from a Single Cancer Center

To evaluate the safety and efficacy of neoadjuvant therapy (NAT), followed by surgical resection in patients with pancreatic ductal adenocarcinoma (PDAC) aged ≥75 years. Whether administration of NAT, followed by surgical resection in elderly patients with PDAC is safe and effective is unknown. The present study is a three-part comparison of older (≥75 years) versus younger (<75 years) patients in different settings throughout the continuum of PDAC care. The first analysis was a comparison of older versus younger consecutive patients with nonmetastatic PDAC who were initiated on FOLFIRINOX. The second was a comparison of older versus younger patients who underwent NAT, followed by surgical resection, and the third and final analysis was a comparison of older patients who underwent either NAT, followed by surgical resection versus upfront surgical resection. Postoperative complications, overall survival (OS), and time to recurrence (TTR) were compared. Propensity score matching (PSM) analysis was performed to adjust for potential confounders. In the first analysis, a lower proportion of older patients (n = 40) were able to complete the intended neoadjuvant FOLFIRINOX (8) cycles compared with younger patients (n = 214; 65.0% vs 81.4%, P = 0.021). However, older patients were just as likely to undergo surgical exploration as younger patients (77.5% vs 78.5%, P = 0.89), as well as surgical resection (57.5% vs 55.6%, P = 0.70). In the second analysis, PSM was conducted to compare older (n = 54) versus younger patients (n = 54) who underwent NAT, followed by surgical resection. There were no significant differences in postoperative complications between the matched groups. While there was a significant difference in OS between older and younger patients (median OS: 16.43 vs 30.83 months, P = 0.002), importantly, there was no significant difference in TTR (median: 7.65 vs 11.83 months, P = 0.215). In the third analysis, older patients who underwent NAT, followed by surgical resection (n = 48) were compared with similar older patients who underwent upfront surgical resection (n = 48). After PSM, there was a significant difference in OS (median OS: 15.78 months vs 11.51 months, P = 0.037), as well as TTR (median TTR: 8.81 vs 7.10 months, P = 0.046) representing an association with improved outcomes that favored the neoadjuvant approach among older patients alone. This comprehensive three-part study showed that administration of NAT, followed by surgical resection, seems to be safe and effective among patients ≥75 years of age. An aggressive approach should be offered to older adults undergoing multimodal treatment of PDAC.

Selecting between programmed cell death ligand 1 (PD-L1) inhibitor or programmed cell death 1 (PD-1) inhibitor plus chemotherapy as first-line treatment for extensive-stage small cell lung cancer (ES-SCLC) patients urgently needs to be answered. Eligible phase 3 randomized clinical trials evaluating regimens based on PD-1/PD-L1 inhibitors as first-line treatment in ES-SCLC patients were systematically searched on the PubMed and Cochrane Library databases and major international conferences from 01/01/2018 to 18/09/2023. The individual patient data (IPD) were recuperated from the Kaplan-Meier curves of the overall survival (OS) and progression-free survival (PFS) of the included studies using the IPDfromKM method. The reconstructed data were pooled into unified arms, including the PD-L1 inhibitor plus chemotherapy group (PD-L1 group), PD-1 inhibitor plus chemotherapy group (PD-1 group), and PD-1 (L1) inhibitor and chemotherapy plus other (anlotinib group, tiragolumab group, and tremelimumab group). Subsequently, the PD-L1 group was indirectly compared with the other groups. A standard statistical analysis was conducted using the "survival" package for the time-to-event endpoint. The primary outcomes were the OS and PFS of the PD-L1 group and the PD-1 inhibitor group. The secondary outcomes included safety and the 12- and 24-month restricted mean survival time (RMST) of the PD-L1 group and PD-1 group. A total of 9 studies including 11 immunotherapy cohorts were included. No significant difference in PFS (hazard ratio [HR]: 0.96, 95% confidence interval [CI]: 0.86-1.06), OS (HR: 0.94, 95% CI: 0.84-1.05), and 12-month and 24-month RMST for OS (P = 0.198 and P = 0.216, respectively) was observed between the PD-L1 group and the PD-1 group. In contrast, the anlotinib group showed significantly better OS (HR: 0.70, 95% CI: 0.55-0.89), PFS (HR: 0.69, 95% CI: 0.58-0.83), and RMST for OS compared to the PD-L1 group. The tiragolumab group showed similar efficacy to the PD-L1 group. However, the tremelimumab group exhibited inferior efficacy than the PD-L1 group. The incidence of ≥grade 3 treatment-emergent adverse events (TEAEs) was significantly higher in the PD-1 group compared to the PD-L1 group (85.4% vs. 69.6%, P <.001), whereas the incidence of irAEs was similar between the two groups. This reconstructed IPD analysis revealed that PD-1 inhibitors plus chemotherapy achieved similar efficacy to PD-L1 inhibitors plus chemotherapy as first-line treatment in ES-SCLC patients, whereas PD-L1 inhibitors plus chemotherapy had a better safety profile.

Hodgkin Lymphoma in Older Patients- a Retrospective Analysis of the Polish Lyphoma Reasearch Group

BackgroundImmunotherapy is a promising treatment for advanced non-small cell lung cancer (advNSCLC), with several immune checkpoint inhibitors (ICIs) FDA-approved since 2015. As ICI indications expand, disparities in treatment selection could...

7510 Background: We previously demonstrated that PFS may be a candidate surrogate endpoint for OS in ES-SCLC using data from 3 randomized trials (Foster, Cancer 2011). Here, we sought to formally assess the patient- and trial-level surrogacy of PFS using data from 9 additional randomized phase II and III trials conducted by the NCI-funded cancer cooperative groups since 1986. Methods: Individual patient data from all 12 trials (3178 patients: 9 phase III and 3 phase II) were pooled. OS was the primary endpoint in all phase III trials; 3 phase III and 1 phase II trial were positive per protocol. Patient-level surrogacy (Kendall’s tau) was assessed using the Clayton copula bivariate survival model. Trial-level surrogacy was assessed via association of the log hazard ratios on OS and PFS across trials, including: weighted (by trial size) least squares regression of Cox model effects (R² WLS) and weighted (by trial size) correlation of the copula effects (R² Copula). One trial had 4 treatment arms thus 14 total two-arm comparisons were made. Results: With a median follow-up of 41.8 months in the 106 patients still alive, the median OS and PFS across trials were 9.7 months (95% CI: 9.5, 9.9) and 5.7 months (95% CI: 5.5, 5.8), respectively. There were 3120 PFS events in total (2564 disease progressions and 556 deaths without progression). The median time from progression to death was 4.1 months (95% CI: 3.9, 4.3). PFS showed modest association with OS at the patient-level (tau= 0.56) and at the trial-level (R² WLS = 0.58; R² Copula (standard error) = 0.55 (0.29)). The 95% CIs for the predicted HR for OS given observed HR on PFS under a weighted leave-one-out prediction always included the observed HR for OS; however such intervals were wide, suggesting uncertainty on the practical use of PFS as a surrogate for OS in this setting. Conclusions: PFS failed to demonstrate surrogacy for OS in ES-SCLC based on this large pooled analysis. Given that the difference in the median PFS and OS is less than 6 months, we recommend using OS as the primary endpoint in phase III trials of previously untreated ES-SCLC.

Clinical Outcomes and Toxicity Profile of Chemoradiotherapy in Older Versus Younger Patients With Anal Cancer: A Retrospective Cohort Analysis.