Dataset Information

Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden.

ABSTRACT:

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.

SUBMITTER: Paz-Ares L

PROVIDER: S-EPMC10870117 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden.

Paz-Ares Luis L Garassino Marina Chiara MC Chen Yuanbin Y Reinmuth Niels N Hotta Katsuyuki K Poltoratskiy Artem A Trukhin Dmytro D Hochmair Maximilian J MJ Özgüroğlu Mustafa M Ji Jun Ho JH Statsenko Galina G Conev Nikolay N Bondarenko Igor I Havel Libor L Losonczy György G Xie Mingchao M Lai Zhongwu Z Godin-Heymann Nadia N Mann Helen H Jiang Haiyi H Shrestha Yashaswi Y Goldman Jonathan W JW

Clinical cancer research : an official journal of the American Association for Cancer Research 20240201 4

<h4>Purpose</h4>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).<h4>Experimental design</h4>Patients were randomized (1:1:1) to durvalumab (1,500 mg) plus EP, durvalumab plus tremelimumab (75 mg) plus EP, or EP alon ...[more]

PMID: 37801329

Similar Datasets

Project description:IntroductionIn the phase 3 study involving the use of durvalumab with or without tremelimumab in combination with platinum-based chemotherapy in untreated extensive-stage SCLC (CASPIAN study), first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone (p = 0.0047). We report exploratory subgroup analyses of treatment patterns and outcomes according to the presence of baseline brain or central nervous system metastases.MethodsPatients (WHO performance status 0 or 1), including those with asymptomatic or treated-and-stable brain metastases, were randomized to four cycles of durvalumab plus EP followed by maintenance durvalumab until progression or up to six cycles of EP and optional prophylactic cranial irradiation. Prespecified analyses of OS and progression-free survival (PFS) in subgroups with or without brain metastases used unstratified-Cox proportional hazards models. The data cutoff was on January 27, 2020.ResultsAt baseline, 28 out of 268 patients (10.4%) in the durvalumab plus EP arm and 27 out of 269 patients (10.0%) in the EP arm had known brain metastases, of whom 3 of 28 (10.7%) and 4 of 27 (14.8%) had previous brain radiotherapy, respectively. Durvalumab plus EP (versus EP alone) prolonged OS (hazard ratio, 95% confidence interval) in patients with (0.79, 0.44-1.41) or without (0.76, 0.62-0.92) brain metastases, with similar PFS results (0.73, 0.42-1.29 and 0.80, 0.66-0.97, respectively). Among patients without brain metastases, similar proportions in each arm developed new brain lesions as part of their first progression (8.8% and 9.5%), although 8.3% in the EP arm received prophylactic cranial irradiation. Similar proportions in each arm received subsequent brain radiotherapy (20.5% and 21.2%), although more common in patients with than without baseline brain metastases (45.5% and 18.0%).ConclusionsThe OS and PFS benefit with first-line durvalumab plus EP were maintained irrespective of the presence of brain metastases, further supporting its standard-of-care use.

Project description:BackgroundThe latest published CASPIAN trial demonstrated that adding durvalumab to etoposide and platinum (EP) improved survival dramatically for patients with extensive-stage small cell lung cancer (ES-SCLC). Considering the high cost of durvalumab, this study evaluated the cost-effectiveness of durvalumab plus EP (DEP) in the first-line setting for treatment-naïve patients with ES-SCLC from the U.S. payer perspective.Materials and methodsWe developed a three-state Markov model to simulate the disease course and source consumption of ES-SCLC over a lifetime horizon. Pseudo-individual patient-level data were generated from digitized Kaplan-Meier curves. Direct medical costs, including drug and administration costs, disease management and adverse events treatment fees, best supportive care and terminal care costs were obtained from sources including the Centers for Medicare and Medicaid Services, Healthcare Cost and Utilization Project, and relevant literature. Health state utility values were derived from published literature. Main outcomes considered were total costs, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). All costs were adjusted for inflation to reflect 2019 U.S. dollars. The willingness-to-pay threshold was set as $150,000/QALY. One-way and probabilistic sensitivity analyses were used to explore the uncertainty of model assumptions.ResultsCompared with EP, DEP was projected to increase life expectancy by 0.86 LYs (1.73 vs. 0.87) and 0.44 QALYs (0.93 vs. 0.49). The incremental treatment cost was $95,907, and the corresponding ICER was $216,953/QALY. The result was most sensitive to the variation of durvalumab acquisition cost. Probabilistic sensitivity analysis revealed that the probability of DEP over EP regimen to be cost-effective was 9.4% at a willingness-to-pay threshold of $150,000/QALY. In the case of reducing the price of durvalumab by 30.7%, DEP was more cost-effective than EP.ConclusionFrom the perspective of the U.S. payer, adding durvalumab to EP is estimated to be not cost-effective compared with EP alone for patients with untreated ES-SCLC.Implications for practiceThe information provided by this analysis serves as a reference for decision makers. Lowering the price of durvalumab would be a potential measure to improve the economics of durvalumab plus etoposide and platinum (DEP), and the inclusion of durvalumab in the Medicare pharmacopeia could make DEP more economically available. These results may also guide physicians and patients to choose the most economically feasible treatment.

Project description:BackgroundImmunotherapy 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.MethodsWe 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).ResultsBetween 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.ConclusionsOur research revealed that there were no significant differences in efficacy or prognosis between PD-1 inhibitor + EP chemotherapy and PD-L1 inhibitor + EP chemotherapy. The two groups seemed to have comparable safety profiles, but the number of discontinuation or death events was too small to draw a firm conclusion.

Dataset Information

Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden.

Purpose

Experimental design

Results

Conclusions

Publications

Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden.

Similar Datasets

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