Updated results of the phase III CASPIAN trial confirm the previously reported survival benefit obtained from adding durvalumab to platinum-etoposide in the first line treatment of patients with extensive-stage small cell lung cancer patients. The further addition of tremelimumab did not lead to an improved outcome.
‘Before the advent of immunotherapy, the treatment and outcome of small cell lung cancer had not improved over more than three decades. Last year the results of the CASPIAN study were published that showed an overall benefit from the addition of durvalumab (PD-L1 inhibitor) to standard cisplatin-etoposide treatment. The current updating publication confirms the longer-term overall survival benefit; the addition of tremelimumab (CTLA-4 inhibitor) does not provide additional benefit. Similar results were obtained with atezolizumab (Liu SV et al. J Clin Oncol. 2021). Therefore, the combination of durvalumab or atezolizumab with platinum-etoposide is the current standard first-line treatment for extensive disease SCLC.’
Small cell lung cancer (SCLC) is the most aggressive form of lung cancer, accounting for 15% of all lung cancer cases. Extensive-stage SCLC carries a further dismal prognosis, with a 2-year survival rate of less than 5% with current standard-of-care platinum-doublet chemotherapy regimens. Dual checkpoint blockade with PD-1/PD-L1 and CTLA-4 inhibitors is an effective treatment strategy in several tumour types, including non-small cell lung cancer. Dual checkpoint inhibition in combination with chemotherapy was suspected to be even more efficacious, with the phase III CASPIAN trial assessing this combination.
The study randomised 805 treatment-naïve ES-SCLC patients (1:1:1) to receive up to 6 cycles of etoposide with either carboplatin or cisplatin alone (EP), or in combination with 4 cycles of durvalumab (1500 mg every 3 weeks), with (DT-EP) or without (D-EP) tremelimumab (75 mg every 3 weeks). Participants receiving EP alone were eligible for prophylactic cranial irradiation at the investigators’ discretion. An interim analysis found treatment with D-EP to be associated with a statistically superior overall survival (OS), compared to EP alone (HR[95%CI]: 0.73[0.59-0.91], P= 0.0047).
The median age of participants of this study was 63 years, 72% were male, 94% had a current or former smoking history and 91% had stage IV disease at diagnosis. At the time of this analysis, 11% of DT-EP patients and 12% of D-EP patients remained on treatment. With a median follow-up for OS of 25.1 months, the significant OS benefit with D-EP compared to EP alone was sustained with a median OS of 12.9 and 10.5 months, respectively (HR[95%CI]: 0.75[0.62-0.91], P= 0.0032). This sustained OS benefit was observed across all prespecified patient subgroups. In contrast, the addition of tremelimumab to D-EP did not significantly improve the OS vs. EP (median OS 10.4 vs. 10.5 months; HR[95%CI]: 0.82[0.68-1.00], P= 0.045). The median PFS was similar throughout all three treatment arms (DT-EP: 4.9 months; D-EP: 5.1 months; EP: 5.4 months). The most common ≥grade 3 adverse events (AEs) were neutropenia (DT-EP: 32%; D-EP: 24%; EP: 33%), anaemia (DT-EP: 13%; D-EP: 9%; EP: 18%). Serious AEs occurred in 45%, 32% and 36% of each treatment arm. Treatment-related deaths occurred in 5% DT-EP patients, in 2% of D-EP patients 1% of EP patients. ≥grade 3 immune-mediated AEs occurred in 14%, 5% and <1%, respectively.
Goldman J, et al. Durvalumab, with or without tremelimumab, plus platinum–etoposide versus platinum–etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomized, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65.