Patients with extensive-stage small-cell lung cancer, a rare type of lung cancer, now have a new first-line treatment option with Imfinzi (durvalumab), a PD-L1 inhibitor, in combination with chemotherapy, according to new results presented at the 2020 ASCO annual meeting. This new combination has been shown to improve survival for these patients, who do not have many treatment options and whose prognosis (survival outlook) is less than 5 years.
The majority (about 85%) of patients with lung cancer have non–small-cell lung cancer (NSCLC). Only about 15% of lung cancers are small-cell lung cancer, and about two-thirds (33%) of patients who are diagnosed with small-cell lung cancer have extensive-stage disease.
The recent PD-1 or PD-L1 inhibitors that have been approved by the FDA for lung cancer were approved for NSCLC, not small-cell lung cancer.
The updated results of the phase 3 clinical trial CASPIAN continue to show that adding the immunotherapy durvalumab to standard chemotherapy prolongs overall survival in newly diagnosed patients with extensive-stage small-cell lung cancer, according to Luis G. Paz-Ares, MD, PhD, Chair of the Medical Oncology Department at Hospital Universitario in Madrid, Spain.
“This is an effective first-line treatment in the extensive-stage setting, where improving outcomes has been a challenge, and so few patients survive 5 years,” said Dr. Paz-Ares, who led the CASPIAN clinical trial and presented the updated results at the ASCO meeting.
“The results support the use of the PD-L1 inhibitor in combination with etoposide plus either cisplatin or carboplatin as a new frontline standard of care for this patient population,” he added.
Based on the results from the CASPIAN study, in March 2020, the FDA approved the use of durvalumab in combination with etoposide chemotherapy plus cisplatin or carboplatin chemotherapy, as a first-line therapy for patients with extensive-stage small-cell lung cancer. This is the first immunotherapy to be approved for patients with this type of small-cell lung cancer, who have few treatment options.
Although about 80% of patients with extensive-stage small-cell lung cancer initially respond to standard chemotherapy with cisplatin or carboplatin, within 6 months of treatment the cancer relapses in most patients.
Before this approval, the average overall survival for patients with this type of lung cancer was only 10 months.
This updated analysis of the CASPIAN study confirms the long-term benefits of adding durvalumab to chemotherapy for the initial treatment of patients with extensive-stage small-cell lung cancer.
At an average follow-up of about 2 years (25.1 months), the average survival was 12.9 months in patients who received durvalumab plus etoposide chemotherapy with cisplatin or carboplatin (the experimental group) compared with 10.5 months for patients who received chemotherapy alone (the control group), which translated to a 25% improvement in survival.
“Survival at 2 years improves from 14% [of patients] in the control arm to 22% in the experimental arm. The magnitude of the benefit was similar and very consistent across all the prespecified subgroups of patients analyzed, including those treated with cisplatin or those patients with liver or brain metastases,” Dr. Paz-Ares said.
The CASPIAN study included 805 patients with extensive-stage small-cell lung cancer, including patients who had metastases (cancer spreading) to the brain or liver. The patients were divided into 1 of the 3 treatment groups, using different chemotherapy regimens, with and without durvalumab. The study evaluated the impact of adding durvalumab to chemotherapy compared with chemotherapy alone, using different treatment combinations.
The overall survival was not significantly different based on the type of chemotherapy that was used with durvalumab, but rather based on the addition of durvalumab to the currently used chemotherapy.
“These data reinforce durvalumab plus chemotherapy as an important new standard of care for extensive-stage small-cell lung cancer patients, and this regimen offers patients convenient dosing every 4 weeks during maintenance,” said José Baselga, MD, PhD, Executive Vice-President of Research & Development Oncology with AstraZeneca, the manufacturer of durvalumab.
The safety was consistent with the known side effects associated with the drugs used in each treatment regimen, including durvalumab and the different chemotherapies.
The most common side effects with durvalumab in patients with extensive-stage small-cell lung cancer were nausea, fatigue or asthenia, and hair loss.
Side effects leading to treatment discontinuation occurred in 10.2% of patients who received durvalumab combined with etoposide chemotherapy plus cisplatin or carboplatin chemotherapy compared with 9.4% in those who received chemotherapy alone. However, 6 deaths occurred in the durvalumab plus chemotherapy group compared with 2 in the chemotherapy group alone.
- About 15% of lung cancers are small-cell lung cancer, and about 33% of patients have extensive-stage small-cell lung cancer
- The combination of durvalumab plus chemotherapy has been shown as effective first-line treatment for patients with this type of lung cancer
- Adding durvalumab to chemotherapy increased the number of patients who survive more than 5 years
- Before the approval of the durvalumab plus chemotherapy combination, the average overall survival for patients with this type of small-cell lung cancer was 10 months