The Chinese National Medical Products Administration has approved durvalumab plus standard-of-care platinum chemotherapy, in the form of etoposide plus either carboplatin or cisplatin, as a frontline treatment option for patients with extensive-stage small cell lung cancer.
The Chinese National Medical Products Administration has approved durvalumab (Imfinzi) plus standard-of-care (SOC) platinum chemotherapy, in the form of etoposide plus either carboplatin or cisplatin, as a frontline treatment option for patients with extensive-stage small cell lung cancer (SCLC).1
The regulatory decision was supported by data from the phase 3 CASPIAN trial (NCT03043872), which demonstrated that durvalumab resulted in a significant and clinically meaningful improvement in overall survival (OS) vs chemotherapy alone in this population. Moreover, findings from the cohort of Chinese patients proved to be in line with the global results that were reported.
“Today’s approval of [durvalumab] plus chemotherapy brings an important global SOC to patients with extensive-stage SCLC in China, who have had few treatment options and a dire prognosis,” Dave Fredrickson, executive vice president of the Oncology Business Unit, at AstraZeneca, stated in a press release. “Physicians can now offer these patients a well-tolerated immunotherapy regimen with sustained OS and prolonged treatment response, as well as convenient dosing. This is also the first time physicians have had the choice to combine immunotherapy with cisplatin, a preferred chemotherapy in this setting in China.”
In the open-label phase 3 trial, investigators examined the safety and efficacy of durvalumab, with or without tremelimumab, plus platinum-etoposide in the first-line treatment of patient with extensive-stage SCLC.2
To be eligible for enrollment, patients needed to be at least 18 years of age, be treatment naïve, have histologically or cytologically documented extensive-stage disease, a World Health Organization performance status score of 0 to 1, measurable disease per RECIST v1.1 criteria, a life expectancy of at least 12 weeks, a body weight of at least 30 kg, and acceptable organ and marrow function. Notably, patients with brain metastases were permitted.
Exclusion criteria included a history of radiotherapy to the chest, planned consolidation chest radiotherapy, active or prior autoimmune or inflammatory disorders, paraneoplastic syndrome of autoimmune nature that needed systemic treatment, a history of active primary immunodeficiency, and uncontrolled or concurrent illness or active infections.
Study participants were randomized 1:1:1 to receive durvalumab plus platinum/etoposide, durvalumab plus tremelimumab plus platinum/etoposide, or platinum/etoposide alone. Patients were stratified based on the planned platinum agent, carboplatin or cisplatin.
The primary end point of the trial was OS, and key secondary end points included progression-free survival (PFS), objective response, OS at 18 months, PFS at 6 months and 12 months, and safety. PFS and objective response was evaluated per investigator assessment and RECIST v1.1 criteria. Investigators also looked at pharmacokinetics, immunogenicity, as well as symptoms and health-related quality of life.
A total of 972 patients underwent screening and 805 underwent randomization; of these patients, 268 received durvalumab plus platinum/etoposide, 268 were given durvalumab plus tremelimumab and platinum/etoposide, and 269 received platinum/etoposide alone. Patients who received durvalumab received a fixed dose of the agent at 1500 mg every 3 weeks for 4 cycles in combination with chemotherapy and then every 4 weeks as a single agent. Treatment was given until disease progression.
At the time of the interim analysis, the durvalumab plus platinum/etoposide and platinum/etoposide groups were recommended to be unmasked because they met the predefined threshold for statistical significance; durvalumab plus tremelimumab and platinum/etoposide did not meet the threshold.
Baseline demographics and disease characteristics were found to be well balanced between the durvalumab plus platinum/etoposide arm and platinum/etoposide–alone arm. The median age of patients was 63 years and 70% were men. Moreover, 93% were current or former smokers and 90% had stage IV disease at the time of their diagnosis. At baseline, 10% of patients had brain or central nervous system metastases; 39% had liver metastases.
In June 2019, the trial met its primary end point of OS when durvalumab plus chemotherapy resulted in a 27% reduction in the risk of death vs chemotherapy alone (hazard ratio [HR], 0.73; 95% CI, 0.59-0.91; P = .0047). The median OS in the investigative and control arms was 13.0 months (95% CI, 11.5-14.8) and 10.3 months (95% CI, 9.3-11.2), respectively.
Moreover, the durvalumab arm also reported a higher confirmed objective response rate (ORR) vs the control arm, at 68% and 58%, respectively (odds ratio, 1.56; 95% CI, 1.10-2.22). The addition of durvalumab to chemotherapy resulted in a delayed worsening of disease symptoms.
Results from an updated analysis of the trial demonstrated that durvalumab plus chemotherapy had sustained efficacy with longer follow-up of over 2 years.3 The median OS in the investigative and control arms was 12.9 months and 10.5 months, respectively (HR, 0.75; 95% CI, 0.62-0.91; nominal P = .0032). Approximately 22.2% of patients who received durvalumab/chemotherapy were alive at 24 months vs 14.4% of those given chemotherapy alone.
Regarding safety, the combination of durvalumab and chemotherapy proved to be consistent with the toxicity profiles of both medicines. Notably, no patients had treatment-emergent antidrug antibodies to durvalumab.
Findings from the Chinese cohort of the trial were noted to have data that were consistent with findings observed in the overall global trial population. Detailed information will be shared at an upcoming medical meeting.
In March 2020, the FDA approved durvalumab for use in combination with SOC chemotherapy, including etoposide plus either carboplatin or cisplatin, in the frontline treatment of adult patients with extensive-stage SCLC based on data from CASPIAN.4