Purpose: In the CASPIAN trial, first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small cell lung cancer (ES-SCLC). We report exploratory analyses of CASPIAN outcomes by programmed cell death ligand-1 (PD-L1) expression and tissue tumor mutational burden (tTMB). Experimental Design: Patients were randomized (1:1:1) to durvalumab (1,500 mg) plus EP, durvalumab plus tremelimumab (75 mg) plus EP, or EP alone. Treatment effects in PD-L1 and tTMB subgroups were estimated using an unstratified Cox proportional hazards model. Results: The PD-L1 and tTMB biomarker-evaluable populations (BEP) comprised 54.4% (438/805) and 35.2% (283/805) of the intention-to-treat population, respectively. PD-L1 prevalence was low: 5.7%, 25.8%, and 28.3% had PD-L1 expression on ≥1% tumor cells (TC), ≥1% immune cells (IC), and ≥1% TCs or ICs, respectively. OS benefit with durvalumab plus EP versus EP was similar across PD-L1 subgroups, with HRs all falling within the 95% confidence interval (CI) for the PD-L1 BEP (0.47‒0.79). OS benefit with durvalumab plus tremelimumab plus EP versus EP was greater in PD-L1 ≥1% versus <1% subgroups, although CIs overlapped. There was no evidence of an interaction between tTMB and treatment effect on OS (durvalumab plus EP vs. EP, P = 0.916; durvalumab plus tremelimumab plus EP vs. EP, P = 0.672). Conclusions: OS benefit with first-line durvalumab plus EP in patients with ES-SCLC was observed regardless of PD-L1 or tTMB status. PD-L1 expression may prove to be a useful biomarker for combined treatment with PD-(L)1 and CTLA-4 inhibition, although this requires confirmation with an independent dataset. See related commentary by Rolfo and Russo, p. 652

Hepatocellular carcinoma (HCC) has one of the highest mortality rates among solid cancers. Late diagnosis and a lack of efficacious treatment options contribute to the dismal prognosis of HCC. Immune checkpoint inhibitor (ICI)-based immunotherapy has presented a new milestone in the treatment of cancer. Immunotherapy has yielded remarkable treatment responses in a range of cancer types including HCC. Based on the therapeutic effect of ICI alone (programmed cell death (PD)-1/programmed death-ligand1 (PD-L)1 antibody), investigators have developed combined ICI therapies including ICI + ICI, ICI + tyrosine kinase inhibitor (TKI), and ICI + locoregional treatment or novel immunotherapy. Although these regimens have demonstrated increasing treatment efficacy with the addition of novel drugs, the development of biomarkers to predict toxicity and treatment response in patients receiving ICI is in urgent need. PD-L1 expression in tumor cells received the most attention in early studies among various predictive biomarkers. However, PD-L1 expression alone has limited utility as a predictive biomarker in HCC. Accordingly, subsequent studies have evaluated the utility of tumor mutational burden (TMB), gene signatures, and multiplex immunohistochemistry (IHC) as predictive biomarkers. In this review, we aim to discuss the current state of immunotherapy for HCC, the results of the predictive biomarker studies, and future direction.

Background: This cohort study, based on a large sample of extensive hepatectomy cases, aimed to analyze the distribution of hepatectomy-related complications and to develop a predictive model of posthepatectomy liver failure (PHLF). Methods: Data of patients who underwent hepatectomy of ≥3 liver segments at the Eastern Hepatobiliary Surgery Hospital from 2000 to 2016 were collected and analyzed. Information on hepatectomy-related complications was collected and risk factors were analyzed. A total of 1,441 eligible patients were randomly assigned at 3:1 ratio into the derivation (n=1,080) and validation (n=361) cohorts. The multivariable logistic regression model was used to establish the prediction model of PHLF in the derivation cohort. Results: The incidence rates of PHLF, ascites, bile leakage, intra-abdominal bleeding, and abscesses were 58.22%, 10.76%, 11.17%, 9.71%, and 4.16%, respectively. The 90-day perioperative mortality rate was 1.32%. Multivariate analyses found that age, gender, platelet, creatinine, gamma-glutamyltransferase, thrombin time, fibrinogen, hepatitis B e (HBe) antigen positive, and number of resected liver segments were independent prognostic factors of PHLF in the derivation cohort and included in the nomogram. The prediction model demonstrated good discrimination [area under the curve =0.726, 95% confidence interval (CI), 0.696–0.760, P<0.0001] and calibration. Conclusions: Our study showed a high perioperative safety and a low risk of serious complications in patients who underwent major liver resection (MLR) at a large hepatobiliary surgery center. Routine preoperative clinical information can be used to develop a postoperative liver failure risk prediction model for rational planning of surgery.

Background: The response rate and survival improvement for rituximab, a CD20‐targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single‐arm, open‐label phase II study evaluated the survival efficacy of 2 years of rituximab‐maintenance therapy in patients with stage III–IV CD20‐positive MZL who had responded to first‐line R–CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R–CVP warrants further investigation. Methods: Prior to rituximab‐maintenance therapy, patients received 6–8 cycles of first‐line R–CVP therapy for stage III–IV MZL. Rituximab (375 mg/m ² ), cyclophosphamide (750 mg/m ² ), and vincristine (1.4 mg/m ² ; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3‐week cycle, while oral prednisolone (100 mg) was given on days 1–5 of each 3‐week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R–CVP treatment, were prescribed rituximab‐maintenance therapy which was administered intravenously at a dose of 375 mg/m ² every 8 weeks for up to 12 cycles. The primary endpoint was progression‐free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety. Results: 47 patients were enrolled, of whom, 45 (96%) received rituximab‐maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R–CVP first‐line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow‐up of 38.2 months, their observed 3‐year PFS rate was 81%. During the rituximab‐maintenance, 6 PR and 1 SD patients achieved CR following the administration of R–CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS ( P = 0.003) and demonstrated a 3‐year OS rate of 90%. Rituximab‐maintenance therapy was well tolerated, and the common treatment‐emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%). Conclusion: Rituximab‐maintenance therapy following first‐line R–CVP demonstrated good PFS in patients with stage III–IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov : NCT01213095

Background: After the publication of the ABC-02 trial, gemcitabine and cisplatin combination therapy (GP) became the standard first-line treatment for advanced biliary tract cancer (BTC). Despite GP therapy, most patients suffer from disease progression. The ABC-06 trial recommended FOLFOX as a second-line treatment, but its efficacy was modest. In this phase II study, we looked at the efficacy and safety of a second-line modified dose of FOLFIRINOX (mFOLFIRINOX) for patients who had failed first-line gemcitabine-based treatment. Methods: From January 2020 to January 2021, 34 patients with advanced BTC who failed first-line gemcitabine-based chemotherapy were enrolled. We evaluated the clinical efficacy and safety outcomes of mFOLFIRINOX. Results: With a median follow-up duration of 13.4 months, the median progression-free survival and overall survival was 2.8 months (95% confidence interval (CI): 1.6–4.0 months) and 6.2 months (95% CI: 5.0–7.4 months), respectively. The objective response rate was 14.7% with no complete response. The disease control rate was 61.7%, with a disease control duration of 4.2 months. Due to the rapid progression of the disease, approximately half of all patients received less than three cycles of treatment. The most common type of adverse event (AEs) was hematopoietic AEs. The incidence of non-hematopoietic AEs was relatively low. Conclusions: The efficacy of mFOLFIRINOX as a second-line treatment in advanced BTC patients after the failure of gemcitabine-based first-line treatment was replicated, albeit with slightly shorter survival results compared to previous studies. Long-term administration of mFOLFIRINOX with toxicity management might offer a survival benefit.

Background/Aims: The incidence of pancreatic cancer (PC) is gradually increasing among elderly individuals, but there are insufficient clinical data on elderly individuals. To determine the efficacy and safety of chemotherapy, we compared the. the outcomes of elderly patients with unresectable PC. Methods: We enrolled patients aged 75 years or older diagnosed with PC from 1 January 2010 to 30 November 2021. Propensity score matching (PSM) was used to reduce the heterogeneity of the study population. For efficacy evaluation, the median overall survival (OS) was estimated for the chemotherapy and nonchemotherapy groups. Chemotherapy tolerability evaluations were also investigated. Results: The study included 115 patients, 47 of whom received chemotherapy and 68 who did not. After PSM, compared with the nonchemotherapy group, the chemotherapy group had more myocardial infarctions (14.6 vs. 0.0%, p < 0.001) and chronic obstructive pulmonary disease (4.4 vs. 0.0%, p = 0.043). The primary endpoint, median OS, was significantly different in the with vs. without chemotherapy groups (203 vs. 106 days, p = 0.013). In the chemotherapy group, 10 patients (21.3%) discontinued treatment due to adverse events. However, there were no reports of death due to severe adverse events. Conclusions: This study demonstrated that chemotherapy improved median OS among elderly patients. These data could support the use of chemotherapy for elderly patients with unresectable PC.