Dataset Information

Beyond PACIFIC: Real-World Outcomes of Adjuvant Durvalumab According to Treatment Received and PD-L1 Expression.

ABSTRACT: Adjuvant durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). A post hoc exploratory analysis of PACIFIC revealed no OS benefit in the PD-L1 < 1% subgroup. This retrospective analysis assesses the real-world impact of durvalumab on OS according to PD-L1 tumor proportion score (TPS). Patients with stage III, unresectable NSCLC treated by CRT, with available PD-L1 TPS, from 1 March 2018 to 31 December 2020, at BC Cancer, British Columbia, Canada were included. Patients were divided into two groups, CRT + durvalumab and CRT alone. OS and PFS were analyzed in the PD-L1 ≥ 1% and <1% subgroups. A total of 134 patients were included in the CRT + durvalumab group and 117, in the CRT alone group. Median OS was 35.9 months in the CRT + durvalumab group and 27.4 months in the CRT alone group [HR 0.59 (95% CI 0.42-0.83), p = 0.003]. Durvalumab improved OS in the PD-L1 ≥ 1% [HR 0.53 (95% CI 0.34-0.81), p = 0.003, n = 175], but not in the <1% subgroup [HR 0.79 (95% CI 0.44-1.42), p = 0.4, n = 76]. This retrospective study demonstrates a statistically significant improvement in OS associated with durvalumab after CRT in PD-L1 ≥ 1%, but not PD-L1 < 1% NSCLC. Variables not accounted for may have biased the survival analysis. A prospective study would bring more insight.

SUBMITTER: Denault MH

PROVIDER: S-EPMC10453050 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Beyond PACIFIC: Real-World Outcomes of Adjuvant Durvalumab According to Treatment Received and PD-L1 Expression.

Denault Marie-Hélène MH Feng Jamie J Kuang Shelley S Shokoohi Aria A Leung Bonnie B Liu Mitchell M Berthelet Eric E Laskin Janessa J Sun Sophie S Zhang Tina T Ho Cheryl C Melosky Barbara B

Current oncology (Toronto, Ont.) 20230808 8

Adjuvant durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). A post hoc exploratory analysis of PACIFIC revealed no OS benefit in the PD-L1 < 1% subgroup. This retrospective analysis assesses the real-world impact of durvalumab on OS according to PD-L1 tumor proportion score (TPS). Patients with stage III, unresectable NSCLC treated by CRT, with available PD-L1 TPS, from 1 March 2018 to 31 December 2020, at BC Cancer, Br ...[more]

PMID: 37623024

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Project description:BackgroundIn the PACIFIC trial, durvalumab significantly improved progression-free and overall survival (PFS/OS) versus placebo, with manageable safety, in unresectable, stage III non-small-cell lung cancer (NSCLC) patients without progression after chemoradiotherapy (CRT). We report exploratory analyses of outcomes by tumour cell (TC) programmed death-ligand 1 (PD-L1) expression.Patients and methodsPatients were randomly assigned (2:1) to intravenous durvalumab 10 mg/kg every 2 weeks or placebo ≤12 months, stratified by age, sex, and smoking history, but not PD-L1 status. Where available, pre-CRT samples were tested for PD-L1 expression (immunohistochemistry) and scored at pre-specified (25%) and post hoc (1%) TC cut-offs. Treatment-effect hazard ratios (HRs) were estimated from unstratified Cox proportional hazards models (Kaplan-Meier-estimated medians).ResultsIn total, 713 patients were randomly assigned, 709 of whom received at least 1 dose of study treatment durvalumab (n = 473) or placebo (n = 236). Some 451 (63%) were PD-L1-assessable: 35%, 65%, 67%, 33%, and 32% had TC ≥25%, <25%, ≥1%, <1%, and 1%-24%, respectively. As of 31 January 2019, median follow-up was 33.3 months. Durvalumab improved PFS versus placebo (primary-analysis data cut-off, 13 February 2017) across all subgroups [HR, 95% confidence interval (CI); medians]: TC ≥25% (0.41, 0.26-0.65; 17.8 versus 3.7 months), <25% (0.59, 0.43-0.82; 16.9 versus 6.9 months), ≥1% (0.46, 0.33-0.64; 17.8 versus 5.6 months), <1% (0.73, 0.48-1.11; 10.7 versus 5.6 months), 1%-24% [0.49, 0.30-0.80; not reached (NR) versus 9.0 months], and unknown (0.59, 0.42-0.83; 14.0 versus 6.4 months). Durvalumab improved OS across most subgroups (31 January 2019 data cut-off; HR, 95% CI; medians): TC ≥ 25% (0.50, 0.30-0.83; NR versus 21.1 months), <25% (0.89, 0.63-1.25; 39.7 versus 37.4 months), ≥1% (0.59, 0.41-0.83; NR versus 29.6 months), 1%-24% (0.67, 0.41-1.10; 43.3 versus 30.5 months), and unknown (0.60, 0.43-0.84; 44.2 versus 23.5 months), but not <1% (1.14, 0.71-1.84; 33.1 versus 45.6 months). Safety was similar across subgroups.ConclusionsPFS benefit with durvalumab was observed across all subgroups, and OS benefit across all but TC <1%, for which limitations and wide HR CI preclude robust conclusions.

Project description:BackgroundImmunotherapy blocking programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) has revolutionized the treatment of extensive-stage small-cell lung cancer (SCLC), but only with limited real-world efficacy data; evidence from immunotherapy for other pulmonary neuroendocrine carcinoma (PNEC) is scarce.ObjectiveThe purpose of this study is to evaluate the efficacy of receiving PD-1/PD-L1 inhibitors in patients with advanced PNEC and explore factors related to survival prognosis, providing clues for treatment for patients with advanced PNEC.MethodsIn all, 203 patients with advanced PNEC who received PD-1/PD-L1 inhibitors between January 2019 and December 2021 were retrospectively analyzed. Kaplan-Meier curves were constructed for progression-free survival (PFS) and overall survival (OS).ResultsFor the 203 patients, the objective response rate (ORR) was 48.3%, the disease control rate (DCR) was 83.3%, the median PFS (mPFS) was 6.0 months, and the median OS (mOS) was 13.1 months. Among them, the histology was 166 SCLC, 13 large-cell neuroendocrine carcinoma, and 24 other unspecified PNEC. Histologically, no significant difference was observed in PFS (p = 0.240) or OS (p = 0.845). In first-line (1L) treatment (N = 125), patients received chemoimmunotherapy and had an ORR of 64.8%, DCR of 92.0%, mPFS of 6.6 months, and mOS of 14.9 months. In second-line (2L) or later-line setting, the ORR, DCR, mPFS, and mOS were 21.8%, 69.2%, 4.4, and 9.4 months; immunotherapy plus small-molecule antiangiogenic agents showed significantly greater PFS than immunotherapy monotherapy or chemoimmunotherapy (6.4 vs 1.4 vs 3.7 months, p = 0.041). Patients without liver metastasis had superior PFS (7.0 vs 5.1 months, p < 0.001) and OS (19.2 vs 9.6 months, p < 0.001) than those with liver metastasis.ConclusionIn clinical practice, PD-1/PD-L1 inhibitors are effective in patients with advanced PNEC, regardless of the pathological histology. The efficacy of 1L immunochemotherapy is worthy of recognition, and the addition of small-molecule antiangiogenic agents to immunotherapy in 2L or later-line treatment provides a better survival trend.DesignRetrospective study.

Project description:BackgroundThe adverse events (AEs) related to immune checkpoint inhibitors (ICIs) have been mostly described in clinical trials, however, such trials are restricted to selection criteria and the results cannot wholly represent the real-world setting. We aimed to evaluate the real-world endocrine AEs associated with programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) inhibitors in Chinese population.MethodsThis retrospective study included cancer patients who were treated with PD-1/PD-L1 inhibitors between January 2018 and December 2020 at Xinqiao Hospital, the Third Military Medical University. The information of 581 patients was reviewed, and data on clinical characteristics, PD-1/PD-L1 use, occurrence of endocrine AEs, and response to PD-1 blockade treatment were collated. The definition of endocrine AEs relied on diagnostic tests. Fisher's exact test or Pearson's chi-squared test was used to analyze the associations between endocrine variables and several categorical variables. Multivariate analyses were performed using a logistic regression model.ResultsEndocrine AEs were observed in 116 of the 581 patients (20.0%). The median time to onset of endocrine AEs was approximately 12 weeks. Pembrolizumab was associated with a significantly higher incidence of endocrine AEs compared to other anti-PD-1 agents (38.5%; P=0.0002); PD-1/PD-L1 inhibitor treatment combined with antiangiogenic therapy or with two other therapies (chemotherapy and antiangiogenic therapy) was associated with a significantly increased occurrence of endocrine AEs, compared to PD-1 blockade treatment alone (41.2%; P=0.015), both based on multivariate analysis. Patients who developed endocrine AEs had significantly higher overall response rates (ORRs; 33.3% vs. 23.1%, P=0.045) and disease control rates (DCRs; 91.1% vs. 79.1%, P=0.008) compared to patients without endocrine AEs. In multivariate analysis, endocrine AEs remained an independent factor for both ORR (OR: 1.764, 95% CI: 1.052-2.957, P=0.031) and DCR (OR: 2.896, 95% CI: 1.324-6.332, P=0.008) after adjusting for the confounding factors.ConclusionsA real-world Chinese population receiving PD-1/PD-L1 treatment, pembrolizumab administrated and triple therapy treatment modalities had a higher incidence of endocrine AEs. Patients who developed endocrine AEs demonstrated a favorable response to PD-l blockade treatment.

Dataset Information

Beyond PACIFIC: Real-World Outcomes of Adjuvant Durvalumab According to Treatment Received and PD-L1 Expression.

Publications

Beyond PACIFIC: Real-World Outcomes of Adjuvant Durvalumab According to Treatment Received and PD-L1 Expression.

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