BACKGROUND: The optimal subsequent treatment strategy for locally advanced non-small cell lung cancer (LA-NSCLC) after chemoradiotherapy (CRT) and consolidative durvalumab therapy remains unknown. We aimed to determine the optimal subsequent treatment strategy for this clinical population.
METHODS: We retrospectively enrolled 523 consecutive patients with LA-NSCLC treated with CRT and analyzed the treatment outcomes of subsequent therapy after progression following CRT and consolidative durvalumab therapy. Patients who received tyrosine kinase inhibitors as subsequent therapy were excluded.
RESULTS: Out of 122 patients who received subsequent chemotherapy, 55% underwent platinum-based, 25% non-platinum-based, and 20% immune checkpoint inhibitor (ICI)-containing therapies. In the platinum-based group, patients with a durvalumab-progression-free survival (Dur-PFS) ≥ 1 year had a significantly longer median subsequent therapy-PFS (SubTx-PFS) than those with Dur-PFS < 1 year (13.2 months vs. 4.7 months; hazard ratio, 0.45; 95% confidence interval, 0.21-0.97; P = .04). Furthermore, among patients receiving non-platinum-based chemotherapy, the median SubTx-PFS was longer in the combined with angiogenesis inhibitor group than in the without group, although the difference was not statistically significant. No significant difference of SubTx-PFS was observed between the reason for durvalumab discontinuation and the outcomes of ICI-containing therapy.
CONCLUSIONS: In clinical practice, platinum-based chemotherapy rechallenge is frequently employed following progression subsequent to CRT and consolidative durvalumab therapy for LA-NSCLC. Optimal treatment strategies may consider Dur-PFS and angiogenesis inhibitor feasibility. Further research is warranted to identify clinical biomarkers that can help identify patients who would benefit from ICI rechallenge.

UNASSIGNED: While the use of immunotherapy has revolutionised the treatment of various cancers, it is often associated with a myriad of immune-related adverse effects.
UNASSIGNED: In this article, we report a rare case of durvalumab-induced triple-M syndrome in a 69-year-old woman with stage III lung adenocarcinoma. She was admitted with profound generalised muscle weakness, myalgia, and exertional breathlessness, about a week into her second cycle of durvalumab, an immune checkpoint inhibitor. She had clinicopathological features of myositis, myasthenia and myocarditis with acute onset symptomatic tri-fascicular block on electrocardiogram, requiring urgent cardiology intervention. Durvalumab was discontinued and she was treated with a combination of high-dose steroids and intravenous immunoglobulin after which she had clinical and biochemical improvement, albeit with residual muscle weakness.
UNASSIGNED: Myocarditis-myositis-myasthenia complex is a rare side effect of immunotherapy which has been reported in other immune checkpoint inhibitors, but less so with durvalumab. We report this clinical case to raise awareness of this rare and potentially life-threatening adverse effect of this agent.
CONCLUSIONS: Triple-M syndrome is a rare immune-related adverse effect, which has been noted in other immune checkpoint inhibitors, but less so with durvalumab specifically.Immunotherapy-induced myositis, myocarditis and myasthenia can occur in isolation or, rarely, in association as a syndrome.This case demonstrates the potentially life-threatening nature of this entity, the need for early recognition, and multi-specialist teamwork to ensure good outcome.

UNASSIGNED: Immune checkpoint inhibitor plus platinum-etoposide (PE) improved overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). While the CASPIAN trial demonstrated the efficacy of durvalumab plus PE, the clinical trial results may not be representative of the general, real-world population because clinical trials often have strict inclusion and exclusion criteria. We herein report the efficacy and safety of durvalumab plus PE in patients with ES-SCLC in real-world, clinical practice.
UNASSIGNED: The present, monocentric, retrospective study evaluated patients with ES-SCLC or recurrent, limited-stage SCLC who received durvalumab plus PE between September 2020 and February 2023. The efficacy and incidence of adverse events (AEs) were also evaluated.
UNASSIGNED: The study included 40 patients, of whom 17 were elderly (age >70 years), and 15 had performance status (PS) 2 or 3. The median follow-up time was 13.0 months [95% confidence interval (CI): 8.0-22.2 months]. The objective response rate was 80.0% (95% CI: 63.1-91.6%), and the disease control rate was 88.6% (95% CI: 73.3-96.8%). The median progression-free survival (PFS) was 5.9 months (95% CI: 4.9-6.9), and the median OS was 25.4 months (95% CI: 4.6-46.2). Factors such as advanced age, poor PS, and presence of brain metastases were not associated with lower PFS and OS. Twenty-six patients (65.0%) experienced grade 3 or higher AEs, mainly hematological toxicity. AEs leading to treatment discontinuation occurred in three patients (8%).
UNASSIGNED: Durvalumab plus PE in patients with ES-SCLC showed good efficacy and safety according to our real-world data, suggesting that this treatment is well tolerated in clinical practice, even in elderly patients and those with poor PS.

UNASSIGNED: We performed a systematic review and meta-analysis to further explore the impact of the addition of immunotherapy to gemcitabine-cisplatin as first-line treatment for advanced biliary tract cancer (BTC) patients.
UNASSIGNED: Literature research was performed, and hazard ratio values and 95% confidence intervals were calculated. Heterogeneity among studies was assessed using the tau-squared estimator ( τ 2 ) . The total Cochrane Q test (Q) was also assessed. The overall survival rate, objective response rate, and progression-free survival in the selected studies were assessed.
UNASSIGNED: A total of 1,754 participants were included. Heterogeneity among the studies selected was found to be non-significant (p = 0.78; tau2 = 0, I2 = 0%). The model estimation results and the forest plot suggested that the test for the overall effect was significant (Z = -3.51; p< 0.01).
UNASSIGNED: The results of the current meta-analysis further confirm the role of immune checkpoint inhibitors plus gemcitabine-cisplatin as the new standard first-line treatment for advanced BTC patients.
UNASSIGNED: https://www.crd.york.ac.uk/prospero, identifier CRD42023488095.

BACKGROUND: It is unclear how the duration and tapering pattern of corticosteroid therapy for pneumonitis changed after the introduction of durvalumab consolidation therapy.
METHODS: We retrospectively evaluated the medical records of patients diagnosed with nonsmall cell lung cancer who received chemoradiotherapy between January 2014 and December 2020.
RESULTS: Data for 135 patients treated before durvalumab approval and 100 patients treated with durvalumab after its approval were analyzed. In both groups, more than 70% were male, with a median age of 66 y. Approximately 85% were smokers, and the most common tumor histology was adenocarcinoma. Most patients were treated with doses of 60 and 66 Gy (n = 127 [94%] vs. n = 95 [95%]). Among the patients treated with durvalumab, 57%, 38%, and 5% had grade 1, grade 2, and grade 3 pneumonitis; none had grade 4 or 5 pneumonitis. Patients treated with durvalumab exhibited a longer duration of corticosteroid therapy for pneumonitis (17 wk; range: 2-88 wk) than patients not treated with durvalumab (7 wk; range: 0.4-21 wk; P < 0.001). Pneumonitis relapse was more frequent in patients treated with durvalumab (n = 8; 23%) than in patients not treated with durvalumab (n = 2; 7%). Among the 8 patients treated with durvalumab, 2 had recurrent pneumonitis, 1 could not terminate corticosteroids.
CONCLUSIONS: Our data show that durvalumab prolongs the duration of corticosteroid therapy and increases the complexity of corticosteroid tapering patterns. This study can help manage pneumonitis caused by immune checkpoint inhibitors and other drugs used after chemoradiotherapy in routine practice and clinical trials.

BACKGROUND: Small cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma responsible for 200,000 deaths per year worldwide. Platinum-etoposide-based chemotherapy has been the standard of treatment for the past 40 years, with an overall survival of 10 months. Since 2019, the addition of immunotherapy (atezolizumab or durvalumab) to chemotherapy has become the standard of care for first-line treatment of extensive-stage SCLC following the demonstration of an improvement in overall survival in phase 3 studies. We aimed to evaluate the efficacy and safety of chemo-immunotherapy compared with chemotherapy alone in a \"real-world\" setting.
METHODS: Retrospective observational study including patients undergoing first-line treatment for extensive-stage SCLC between 2014 and 2022. We separated the study population into two arms (chemo-immunotherapy/chemotherapy). For each arm, progression-free survival (PFS), overall survival (OS) and serious side effects were collected. Associations between treatments and survival outcomes were adjusted for potential confounders. Consolidative palliative thoracic radiotherapy was introduced in the models as a time-dependent variable.
RESULTS: A total of 118 patients with a median age of 63 years were included. 65.2 % of patients were performance status 0 or 1. In univariate analysis, PFS and OS were not significantly different between the chemo-immunotherapy and chemotherapy alone groups (p = 0.70 and 0.24 respectively). In multivariate analysis, the addition of immunotherapy to chemotherapy was not significantly associated with better PFS (HR 0.76, IC (0.49 - 1.19), p = 0.23), but it was significantly associated with better OS (HR 0.61, IC (0.38 - 0.98), p = 0.04). Consolidative palliative thoracic radiotherapy (time-dependent variable), when applied (almost only in the chemotherapy alone group), was significantly associated with better PFS and OS.
CONCLUSIONS: In this real-world study, chemo-immunotherapy was associated with slightly better OS compared to chemotherapy alone as a first-line treatment in ES-SCLC patients in multivariate analysis, which is not explained by a benefit in PFS. However, consolidative palliative thoracic radiotherapy seems to be significantly associated with better OS and PFS, suggesting that we should also consider using it in patients receiving chemo-immunotherapy.

Evidence from the Phase III PACIFIC trial established durvalumab, a monoclonal antibody (mAb) targeting PD-L1, following concurrent chemoradiotherapy (cCRT) as a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). There remains an unmet need to improve upon the outcomes achieved with the PACIFIC regimen. Combining durvalumab with other immunotherapies may improve outcomes further. Two such immunotherapies include oleclumab, an mAb targeting CD73, and monalizumab, an mAb targeting NKG2A. Both agents demonstrated antitumor activity in early-phase trials. PACIFIC-9 (NCT05221840) is an international, double-blind, randomized, placebo-controlled, Phase III trial comparing durvalumab plus either oleclumab or monalizumab with durvalumab plus placebo in patients with unresectable, stage III NSCLC and no disease progression following cCRT.Clinical Trial Registration: NCT05221840 (ClinicalTrials.gov).
Durvalumab is a treatment that helps the body\'s immune system to identify and attack cancer cells by binding to a protein called PD-L1. Studies show that durvalumab lowers the risk of cancer growing or spreading, and prolongs survival, when administered after chemotherapy and radiation therapy (‘chemoradiotherapy’) in patients with a type of lung cancer called stage III non-small-cell lung cancer (NSCLC) for whom surgery is not an option.Two antibody treatments have been developed that may help a patient\'s immune system to identify and attack cancer cells. Oleclumab binds to a protein on cancer cells called CD73, which prevents the production of adenosine, a chemical that obstructs the immune system from attacking the cancer. Monalizumab binds to NKG2A, a protein on immune cells that inhibits their ability to destroy cancer cells. Early studies suggest that combining either of these treatments with durvalumab may be better than durvalumab alone for slowing the growth and spread of cancer in patients with NSCLC.PACIFIC-9 is a study that aims to recruit approximately 999 patients with stage III NSCLC for whom surgery is not an option and who have completed chemoradiotherapy without the cancer growing or spreading. Patients will be randomly assigned in equal numbers to receive up to a year of treatment with durvalumab plus oleclumab, durvalumab plus monalizumab or durvalumab plus placebo. The primary measure of efficacy is the length of time that patients remain alive without the cancer growing or spreading for each combination versus durvalumab plus placebo.

UNASSIGNED: Although programmed death ligand 1 (PD-L1) inhibitor plus chemotherapy regimen is a promising strategy for malignant tumors, it can induce significant immune-related adverse events, such as immune-related pneumonitis. Here, we report the first case of lethal immune-related pneumonitis in an Asian patient receiving anti-PD-L1 treatment.
UNASSIGNED: A 68-year-old man was diagnosed with small cell lung cancer and interstitial pneumonia. After his pulmonary infection was relieved by comprehensive treatment, the patient received first-line treatment with durvalumab plus etoposide and carboplatin. Two weeks after starting durvalumab treatment, the patient had chest pain and shortness of breath. He was diagnosed with immune-induced pneumonia and treated with methylprednisolone, cefoperazone, and sulbactam, followed by oxygen and pirfenidone. Oxygen partial pressure decreased to 58 mm Hg within next the 4 days and laboratory assessment suggested cytokine storm. The patient underwent 2 plasma exchanges, one double filtration plasmapheresis and oxygen saturation decreased continuously. The patient died 1 month after durvalumab treatment.
UNASSIGNED: Immune-related pneumonitis induced by PD-L1 inhibitors is rare but life-threatening. Infection should be ruled out before starting immunotherapy.

BACKGROUND: In the AEGEAN trial, neoadjuvant durvalumab plus platinum-based chemotherapy (D+CT) followed by adjuvant durvalumab, versus neoadjuvant chemotherapy alone, significantly improved pathological complete response (pCR) rate and event-free survival (EFS) in patients with resectable NSCLC. In the PACIFIC trial, consolidation durvalumab significantly improved progression-free (PFS) and overall survival (OS) for patients with unresectable stage III NSCLC after chemoradiotherapy. Strong pathological and clinical outcomes with chemoimmunotherapy have generated interest in its use to enable patients with borderline-resectable NSCLC to undergo surgery. Additionally, for patients initially deemed resectable but who later become unresectable/inoperable during neoadjuvant treatment, consolidation immunotherapy after chemoradiotherapy should be explored.
METHODS: MDT-BRIDGE (NCT05925530) is a multicenter, phase II, non-randomized study in ∼140 patients with EGFR/ALK wild-type, stage IIB-IIIB (N2) NSCLC. Following baseline multidisciplinary team (MDT) assessment to determine resectable/borderline-resectable status, all patients receive 2 cycles of neoadjuvant D+CT every 3 weeks, followed by MDT reassessment of resectability. Patients deemed resectable receive 1-2 additional cycles of D+CT followed by surgery (Cohort 1). Patients deemed unresectable receive standard-of-care chemoradiotherapy (Cohort 2). Cohort 1 patients who become ineligible for surgery can enter Cohort 2. Following surgery or chemoradiotherapy, patients receive adjuvant or consolidation durvalumab for 1 year. The primary endpoint is resection rate in all patients. Additional endpoints include resection rates by baseline resectable/borderline-resectable status, resection outcomes, EFS/PFS, OS, pCR rate, circulating tumor DNA dynamics pre- and post-surgery (including correlation with clinical outcomes), and safety.
CONCLUSIONS: Enrollment began in February 2024; primary completion is anticipated in April 2026.

BACKGROUND: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination\'s real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes.
METHODS: We included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia). The primary endpoint was overall survival (OS).
RESULTS: 666 patients were enrolled. Median OS was 15.1 months and median PFS was 8.2 months. The investigator-assessed overall response rate was 32.7 %, with stable disease in 45.2 % of patients. High baseline CEA levels, ECOG PS > 0, metastatic disease, and NLR > 3 were associated with poor survival. Any grade adverse events (AEs) occurred in 92.9 % of patients (grade >2: 46.6 %). Immune-related AEs (irAEs) occurred in 20.0 % (grade >2: 2.5 %). Three deaths (0.5 %) were deemed treatment-related, none linked to immunotherapy. Common irAEs were rash (8.2 % all grades; 0.3 % grade >2), itching (10.3 % all grades; 0.2 % grade >2), and hypothyroidism (5.1 % all grades; 0.3 % grade >2). Durvalumab discontinuation rate due to AEs was 1.5 %. ESMO-recommended genes were analyzed and no outcome differences were found. A comparative analysis with a historical cohort of patients treated with chemotherapy alone confirmed the positive survival impact of durvalumab in combination with cisplatin/gemcitabine.
CONCLUSIONS: This first global real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.