November 20, 2020 - Exploratory subgroup analysis of patients with extensive-stage small-cell lung cancer who derived a progression-free survival benefit with durvalumab plus platinum-based chemotherapy lasting longer than 12 months in the CASPIAN trial did not reveal any clinical characteristics that could serve as predictive factors for benefit with the monoclonal antibody.
Patients with extensive-stage small-cell lung cancer (ES-SCLC) who were treated with durvalumab (Imfinzi) plus platinum-based chemotherapy (EP) in the CASPIAN trial derived a long-term benefit 3 times greater than those treated with chemotherapy alone. However, exploratory subgroup analysis of patients who derived a progression-free survival (PFS) benefit lasting longer than 12 months did not reveal any clinical characteristics that could serve as predictive factors for benefit with the monoclonal antibody.1
Further, tumor mutational burden, evaluable in 35% of the intention-to-treat population, was not predictive of an improvement in overall survival (OS) for patients.
“Patients in all treatment arms with PFS greater than 12 months had improved outcomes including exceptional long-term benefit observed with OS rates greater than 75%,” Ju Ho Ji, MD, said in a presentation of the data during the ESMO Asia Congress 2020. “There were no unique clinical characteristics that appear to identify patients who derive long-term benefit.”
Ji is a professor in the Division of Hematology and Oncology at Samsung Changwon Hospital and a professor of medicine at the Sungkyunkwan University School of Medicine in Korea.
Patients with treatment-naïve ES-SCLC enrolled in the phase 3 CASPIAN trial (NCT03043872) received either durvalumab plus tremelimumab with EP (n = 268), durvalumab plus EP (n = 268), or EP alone (n = 269). The addition of the CTLA-4 monoclonal antibody tremelimumab to the combination of durvalumab and EP did not significantly improve outcomes for patients.
In data presented at the 2020 ASCO Virtual Scientific Program, durvalumab plus EP demonstrated sustained improvement in OS at 2-year follow-up compared with EP alone. The median OS was 12.9 months versus 10.5 months, respectively (HR, 0.75; 95% CI, 0.62-0.91; P = .0032).2 The survival rate at 2 years was 22% in the experimental arm compared with 14% in the control arm. The PFS data was not formally tested for statistical significance, however the PFS rates at 2 years favored the combination (11.0% vs 2.9%, respectively).2
PFS lasting at least 12 months was the preliminary threshold to identify potential prognostic factors. In total, 45 of 265 evaluable patients (17%) treated with durvalumab plus chemotherapy experienced a PFS lasting at least 12 months. In the EP alone arm, 12 of 266 evaluable patients (4.5%) met the threshold for analysis. In order to increase the sample size of the subgroup a third subset of patients composed of patients from both the durvalumab plus EP and durvalumab plus tremelimumab and EP arms (immunotherapy [IO] combined). Eighty-seven of 531 evaluable patients (16.4%) were included in the IO combined arm.1
In all response arms for patients with a PFS lasting at least 12 months, investigators observed improved overall response rate (ORR) and duration of response (DOR). Specifically, the confirmed ORR for patients in the durvalumab plus EP arm was 96% and the median time to response was 43 days (range, 33-155). In the EP alone arm, the ORR for 12 patients was 100% with a median time to response of 42.5 days (range, 36-592). The median DOR for the combination was not reached (95% CI, 18–not estimable [NE]) compared with 20 months with EP alone (95% CI, 12–NE). Finally, at 24 months, 54% of patients remained in response in the durvalumab plus EP arm compared with 48% in the EP alone arm.1
“Notably, there were some patients who had baseline brain or liver metastases who derived long-term benefit,” Li noted. Specifically, 7% and 20% of patients with brain and liver metastases, respectively, in the durvalumab plus EP arm experienced PFS lasting at least 12 months, compared with 0% and 17% in the EP alone arm.
In OS analysis for these subgroups, the median OS was not reached across arms and each arm demonstrated an OS benefit of greater than 75%. Specifically, the OS rates for the durvalumab plus EP arm, the IO combined arm, and the EP alone arm were 76.7%, 82.2%, and 83.3%, respectively. In those patients who had a PFS of less than 12 months, the OS rates were 11.1%, 11.0%, and 10.4%, respectively.1
In terms of safety, the incidence of grade 3/4 adverse effects (AEs) was higher in the EP alone arm (75%) compared with the durvalumab plus EP (60%) and IO combined (67%) arms. Treatment-related AEs leading to death as assessed by investigators were observed in 2% of patients in the combination arm. No treatment-related AEs resulted in the death of patients in the EP alone arm.1
Although the subgroup analysis did not reveal a prognostic factor for patients with ES-SCLC, Ji noted that further investigations are ongoing to stratify patients who may have a long-term benefit.
1. Ji JH, Goldman JW, Garassino MC, et al. Durvalumab (D) ± tremelimumab (T) + platinum-etoposide (EP) in 1L ES-SCLC: characterization of long-term clinical benefit and tumour mutational burden (TMB) in CASPIAN. Presented at: European Society for Clinical Oncology Asia Congress 2020; November 20-22, 2020; Virtual. Abstract 379MO.
2. Paz-Ares LG, Dvorkin M, Chen Y, et al. Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): updated results from the phase III CASPIAN study. J Clin Oncol. 2020;38(suppl 15):9002. doi: 10.1200/JCO.2020.38.15_suppl.9002