CASPIAN PROs Support Durvalumab Use For Extensive-Stage SCLC

medwireNews: Patient-reported outcomes (PROs) for the CASPIAN trial add further support for the use of durvalumab alongside etoposide–platinum chemotherapy as front-line treatment for patients with extensive-stage small-cell lung cancer (SCLC). 

The results were reported at the ESMO 2019 Congress in Barcelona, Spain, by Marina Garassino, from the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, who said the secondary PRO endpoints were “consistent with efficacy outcomes in this open-label study.” 

The overall survival (OS) results from the phase III trial showed a significant survival benefit with the PD-L1 inhibitor without greater toxicity, as was presented at the IASLC World Conference on Lung Cancer 2019 and subsequently published in The Lancet. 

Marina Garassino first reported that patients given durvalumab plus etoposide and carboplatin or cisplatin had a comparable rate of first disease progression to those given only the chemotherapy (84.3 vs 86.6%) but had numerically fewer new lesions at the time of progression (41.4 vs 47.2%).  

Of note, the rate of new central nervous system lesions at time of first progression was similar between the groups (11.6 vs 11.5%) despite the optional use of prophylactic cranial irradiation among the patients given only chemotherapy. 

In addition, she presented an exploratory PD-L1 analysis of 277 participants, showing that 80.1% of patients did not have any tumour cell expression and 58.1% no immune cell expression. Based on the low PD-L1 expression in these patients, the researchers chose a PD-L1 cutoff of 1% for the OS analysis. 

But OS benefit with durvalumab was not related to PD-L1 expression at this threshold or when PD-L1 expression was assessed as a continuous variable, and thus “PD-L1 is not a predictive biomarker to select the treatment” for extensive-stage SCLC patients, Marina Garassino said. 

CASPIAN participants were assessed for symptoms, health-related quality of life (HRQoL) and functioning using the EORTC QLQ-C30 and QLQ-LC13 scales at baseline, every 3 weeks during chemotherapy, every 4 weeks until disease progression, and every 8 weeks until second progression, the presenter explained. 

She said that compliance with the assessments was good (60% or better) for up to 84 weeks among the patients in the durvalumab arm and up to 20 weeks for those given only chemotherapy. 

Baseline functioning scores were comparable between the patients given durvalumab plus etoposide–platinum and those given only the chemotherapy, but time to deterioration favoured use of the PD-L1 inhibitor across all the QLQ-C30 scales, including a trend towards better global health status/QoL, and significantly longer durations for the cognitive, emotional, physical, role and social functioning scales (hazard ratio [HR]=0.61–0.81). 

Time to deterioration of symptoms also favoured durvalumab plus chemotherapy over chemotherapy alone for both the EORTC scales, including a significantly longer time to diarrhoea, constipation, appetite loss, dyspnoea, haemoptysis, and pain in the arm/shoulder, chest and other anatomy (HR=0.59–0.76), Marina Garassino concluded. 

Reference 

Paz-Ares L, Goldman JW, Garassino MC, et al. PD-L1 expression, patterns of progression and patient-reported outcomes (PROs) with durvalumab plus platinum-etoposide in ES-SCLC: Results from CASPIAN. ESMO 2019 Congress; Barcelona, Spain: 27 September–1 October. LBA89