BACKGROUND: Atezolizumab is an immune checkpoint inhibitor (ICI) and a frontline treatment of patients with cisplatin-ineligible advanced urothelial carcinoma (UC). There is limited evidence on the prognostic value of patient reported outcomes (PROs) in advanced UC treatment, particularly in the context of ICI therapy.
OBJECTIVE: To investigate the prognostic association of PROs with survival in patients with advanced UC treated with atezolizumab.
METHODS: This study used data from 467 patients with advanced UC initiating atezolizumab in the IMvigor211 trial. Pre-treatment PROs association with overall survival (OS) and progression free survival (PFS) was assessed using Cox proportional hazard analysis. PROs were recorded via the European Organisation for Research and Treatment of Cancer QLQ-C30. Discrimination performance was assessed via the C-statistic (c).
RESULTS: Patient reported physical function, pain, appetite loss, global health, fatigue, role function, constipation, nausea and vomiting, dyspnoea, and insomnia were significantly associated with OS and PFS on univariable and adjusted analysis (P < 0.05). Physical function (c = 0.63), pain (c = 0.63), appetite loss (c = 0.62), global health status (c = 0.62), and fatigue (c = 0.62), were the most prognostic factors of OS. The OS discrimination performance of physical function (c = 0.61) was superior to ECOG PS (c = 0.58). Of patients assessed by investigators as having no performance restrictions (ECOG PS of 0), 38 (18%) and 91 (42%) self-reported low and intermediate physical function scores, respectively.
CONCLUSIONS: Pre-treatment PROs were identified as independent prognostic factors of OS and PFS. Patient-reported physical function was more prognostic of OS than ECOG PS. This highlights a potential for PROs to enable improved patient stratification in ICI trials.

UNASSIGNED: Immune checkpoint inhibitors (ICIs), agents that stimulate T-cell function, have become the standard first-line treatment for unresectable hepatocellular carcinoma (HCC). However, they may also cause immune-related adverse events (irAEs), which are rare and have not been extensively reported. Here, we describe a case of severe febrile neutropenia and pancytopenia after atezolizumab plus bevacizumab (atezo/bev) therapy and its treatment course.
UNASSIGNED: The combination of atezo/bev was initiated as the first-line treatment for a man in his early 50s, who was diagnosed with unresectable HCC. The first treatment cycle was administered in the outpatient setting, and the patient developed a fever of 39.0 ℃ 10 days after therapy initiation. He presented 5 days later with persistent fever as well as a headache, vomiting, chills, generalized pain, fatigue, mild abdominal discomfort, and a burning rash present on his neck and face. Complete blood counts showed severe neutropenia [absolute neutrophil count (ANC) of 90 cells/µL], leukopenia [white blood cell (WBC) count 500 cells/µL], thrombocytopenia [platelet count (PC) 18,000 cells/µL], and mild anemia (hemoglobin level 12.6 gm/dL). Imaging findings showed colitis on computed tomography (CT). Atezo/bev therapy was discontinued. Treatment plan constituted of cefepime and filgrastim, a recombinant form of the naturally occurring granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia, metronidazole for colitis, and intravenous methylprednisolone for immune-related toxicities. The patient fully recovered after 4 days of admission.
UNASSIGNED: In conclusion, we observed temporary severe febrile neutropenia and pancytopenia during systemic immunotherapy in a patient with unresectable HCC. Healthcare providers should consider hematological irAEs (hem-irAEs) in patients after the administration of ICIs.

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Various symptoms emerge as immune-related adverse events of immune checkpoint inhibitor (ICI). A 73-year-old woman, a non-smoker, receiving chemotherapy including atezolizumab for lung adenocarcinoma, presented with fever, bilateral parotid swelling and sicca syndrome after four courses of chemotherapy. Because the lesions were not localized, the diagnosis was ICI-related sialadenitis rather than infectious. Prednisolone improved salivary gland swelling quickly. Six months after the last administration of ICI, there was no obvious progression of lung cancer. To our knowledge, this is the first case of sialadenitis caused by atezolizumab. ICI-related sialadenitis may be a good prognostic marker for lung cancer.

One of the immune-related adverse events from immune checkpoint inhibitors (ICIs) is skin toxicity. Oral corticosteroids are the first-line treatment for severe cutaneous immune-related adverse events. However, corticosteroids may conflict with the efficacy of ICIs. A 55-year-old Japanese man with a history of psoriasis vulgaris was diagnosed with small-cell lung cancer (Stage ⅣA) and administered combined chemoimmunotherapy, including atezolizumab, which resulted in exacerbation of psoriasis. In response, he was treated with biological agents, such as anti-IL-23 and IL-17 antibodies, risankizumab, and secukinumab, respectively, and achieved long-term survival with continued treatment with atezolizumab. This case report suggests that biological agents might be the best course of treatment against autoimmune-related adverse events caused by ICI therapy.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma accounting for 15% of lung cancers with dismal survival outcomes. Minimal changes in therapy and prognosis have occurred in SCLC for the past four decades. Recent progress in the treatment of extensive-stage disease (ES-SCLC) has been marked by incorporating immune checkpoint inhibitors (ICIs) into platinum-based chemotherapy, leading to modest improvements. Moreover, few second-line-and-beyond treatment options are currently available. The main limitation for the molecular study of SCLC has been the scarcity of samples, because only very early diseases are treated with surgery and biopsies are not performed when the disease progresses. Despite all these difficulties, in recent years we have come to understand that SCLC is not a homogeneous disease. At the molecular level, in addition to the universal loss of retinoblastoma (RB) and TP53 genes, a recent large molecular study has identified other mutations that could serve as targets for therapy development or patient selection. In recent years, there has also been the identification of new genetic subtypes which have shown us how intertumor heterogeneity exists. Moreover, SCLC can also develop intratumoral heterogeneity linked mainly to the concept of cellular plasticity, mostly due to the development of resistance to therapies. The aim of this review is to quickly present the current standard of care of ES-SCLC, to focus on the molecular landscapes and subtypes of SCLC, subsequently present the most promising therapeutic strategies under investigation, and finally recap the future directions of ongoing clinical trials for this aggressive disease which still remains a challenge.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) presents significant treatment challenges due to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC.
METHODS: In this non-randomized study, patients with metastatic LCNEC were prospectively enrolled and assigned to receive either standard chemotherapy plus atezolizumab followed by maintenance with atezolizumab or standard chemotherapy alone. The primary outcomes measured were 12- and 24-month survival rates, progression-free survival (PFS), and overall survival (OS) between the two groups.
RESULTS: Of the 22 patients screened, 17 met the inclusion criteria and received either atezolizumab plus platinum-based chemotherapy (n = 10) or chemotherapy alone (n = 7). After a median follow-up of 23.3 months, the 12-month survival rate was 57.1% (95% CI: 32.6-100%) and 14.3% (95% CI: 2.33-87.7%) for the atezolizumab and the chemotherapy-only groups, respectively. The survival benefit for the atezolizumab group was sustained at 24 months (45.7% vs. 14.3%). Overall survival was significantly higher for the atezolizumab group, and PFS was non-significantly associated with the addition of atezolizumab (log-rank p = 0.04 and 0.05, respectively).
CONCLUSIONS: This pilot study suggests that the addition of atezolizumab to standard platinum-based chemotherapy may provide a substantial survival benefit compared with chemotherapy alone in the first-line treatment of metastatic LCNEC.

This epidemiological model forecasted reductions in recurrences and recurrence treatment cost savings with adjuvant atezolizumab vs best supportive care among Canadians with stage II-IIIA non-small cell lung cancer (NSCLC) at national and provincial levels. The population had resected, programmed cell death 1 ligand 1 (PD-L1)-high (≥50%), EGFR-, ALK-, stage II-IIIA NSCLC eligible for adjuvant treatment. Patients with recurrence or death and the costs of treating recurrences were estimated for those receiving adjuvant atezolizumab or best supportive care each year (2024-2034). Proportions of patients expected to be event free up to 10 years after treatment initiation were extrapolated with parametric survival analyses. In the base case analysis, 240 fewer recurrences were estimated to occur over 10 years (2024-2034) with adjuvant atezolizumab vs best supportive care across Canada, with 136 (57%) and 104 (43%) fewer locoregional and metastatic recurrences, respectively. Projected costs of treated recurrences were CAD 33.2 million less over 10 years with adjuvant atezolizumab at a national level (adjuvant atezolizumab, CAD 135.8 million; best supportive care, CAD 169.0 million). This model predicts a considerable long-term reduction in recurrences and substantial treatment cost savings with adjuvant atezolizumab vs best supportive care for patients with PD-L1-high early-stage NSCLC in Canada.

UNASSIGNED: This study aimed to investigate the dynamics of programmed death-ligand 1 (PD-L1) expression, spatial heterogeneity, and binding affinity of FDA-approved anti-PD-L1 antibodies (avelumab and atezolizumab) in gastric cancer. Additionally, we determined how PD-L1 glycosylation impacts antibody accumulation in gastric cancer cells.
UNASSIGNED: Dynamic PD-L1 expression was examined in NCIN87 gastric cancer cells. Comparative binding studies of avelumab and atezolizumab were conducted in gastric cancer models, both in vitro and in vivo. Antibody uptake in tumors was visualized through positron emission tomography (PET) imaging. PD-L1 glycosylation status was determined via Western blot analyses before and after PNGase F treatment.
UNASSIGNED: Consistent findings revealed time-dependent PD-L1 induction in NCIN87 gastric cancer cells and spatial heterogeneity in tumors, as shown by PET imaging and immunofluorescence. Avelumab displayed superior binding affinity to NCIN87 cells compared to atezolizumab, confirmed by in vivo PET imaging and ex vivo biodistribution analyses. Notably, PD-L1 glycosylation at approximately 50 kDa was observed, with PNGase F treatment inducing a shift to 35 kDa in molecular weight. Tissue samples from patient-derived xenografts (PDXs) validated the presence of both glycosylated and deglycosylated PD-L1 (degPD-L1) forms in gastric cancer. Immunofluorescence microscopy and binding assays demonstrated enhanced avelumab binding post-deglycosylation.
UNASSIGNED: This study provides an understanding of dynamic and spatially heterogeneous PD-L1 expression in gastric cancer. Anti-PD-L1 immunoPET was able to visualize gastric tumors, and PD-L1 glycosylation has significant implications for antibody recognition. These insights contribute to demonstrating the complexities of PD-L1 in gastric cancer, holding relevance for refining PD-L1 imaging-based approaches.