According to lead study author Dr. Luis Paz-Ares, study findings confirm the use of the immunotherapy Imfinzi in combination with etoposide plus cisplatin or carboplatin (EP) as a new frontline standard of care for this patient population.
Updated results from the phase 3 CASPIAN trial presented during the 2020 ASCO Virtual Scientific Program show that adding Imfinzi (durvalumab), an immunotherapy that inhibits the cancer-driving protein PD-L1, to standard-of-care chemotherapy continues to demonstrate survival benefits in patients with previously untreated extensive-stage small cell lung cancer (ES-SCLC).
The findings, according to lead study author Dr. Luis Paz-Ares, confirm the use of Imfinzi in combination with the chemotherapy etoposide plus cisplatin or carboplatin (EP) as a new standard initial, or first-line, treatment for this patient population.
“This is an effective first-line treatment in the extensive-stage setting, where improving outcomes has been a challenge and so few patients survive five years,” said Paz-Ares, chair of the medical oncology department at Hospital Universitario Doce de Octubre in Madrid, in a press release from AstraZeneca, the manufacturer of Imfinzi.
Back in March, the Food and Drug Administration approved Imfinzi in combination with etoposide plus cisplatin or carboplatin as a first-line treatment option for adults with ES-SCLC. Imfinzi, a human monoclonal antibody, counters the tumor's immune-evading tactics and reverses the inhibition of immune response.
The agency based its decision on initial findings from the CASPIAN trial, which demonstrated that, after a median follow-up of 14.2 months, adding Imfinzi improved median overall survival to 13 months vs. 10.3 months in patients who had received standard-of-care chemotherapies alone.
Approximately two-thirds of patients diagnosed with small cell lung cancer (SCLC) are diagnosed with ES-SCLC, which means the cancer has spread throughout the lung or to other parts of the body. Prognosis is poor, as 6% of all patients with SCLC will be alive five years after diagnosis.
To evaluate the safety and efficacy of the chemo-immunotherapy combination vs. chemotherapy alone, investigators randomized 805 patients (median age of 63) to one of three treatment arms. Patients received either Imfinzi with etoposide plus carboplatin or cisplatin chemotherapy (268 patients), or Imfinzi and chemotherapy with the addition of tremelimumab (an experimental immunotherapy that is similar to Imfinzi but inhibits the protein CTLA-4) (268 patients), versus chemotherapy alone (269 patients).
Measuring overall survival (OS), or the length of survival from the start of treatment, was the primary goal of the study. Secondary goals included measuring progression-free survival (PFS), or the time from the start of treatment until disease worsened; objective response rate (ORR), or the proportion of complete and partial responses to treatment; safety; and tolerability.
After a median follow-up of 25.1 months, the updated findings show that patients who received Imfinzi plus standard-of-care chemotherapy achieved a median OS of 12.9 months compared with 10.5 months for those who received chemotherapy alone. In comparison, the combination of Imfinzi plus tremelimumab and standard-of-care chemotherapy demonstrated a median OS of 10.4 months.
At 18 months, OS rates reached 32% in the Imfinzi and standard-of-care chemotherapy arm, 30.7% in the Imfinzi plus tremelimumab and standard-of-care chemotherapy arm and 24.8% in the group that received chemotherapy alone. In addition to the lack of OS benefit in the arm that received Imfinzi plus tremelimumab and standard-of-care chemotherapy, the data demonstrated that the regimen also failed to meet other secondary outcomes.
For instance, the median PFS was 4.9 months in patients who received Imfinzi plus tremelimumab and standard-of-care chemotherapy compared with 5.4 months in patients who received chemotherapy alone.
In these updated findings, PFS for the Imfinzi and standard-of-care chemotherapy vs. standard-of-care chemotherapy alone was not formally evaluated for statistical significance. However, patients who received the chemo-immunotherapy combination reached a median PFS of 5.1 months compared with 5.4 months in those who received standard-of-care chemotherapy alone. The ORR was 67.9% in patients who received the combination vs. 58% in those who received chemotherapy alone.
Data regarding safety remained consistent with previously known side effects associated with the agents used in each treatment arm, according to Paz-Ares. Approximately 21% of patients who received Imfinzi plus tremelimumab and standard-of-care chemotherapy had to discontinue treatment compared with 10.2% who received the immuno-chemotherapy combination and 9.4% who received standard-of-care chemotherapy alone.
“We believe (these results) further support (Imfinzi) plus (chemotherapy) as a new standard-of-care treatment for patients with extensive-stage small cell lung cancer treated in the first-line setting,” Paz-Ares said.
A version of this story originally appeared on OncLive® as “Frontline Durvalumab Maintains OS Benefit in Extensive-Stage Small Cell Lung Cancer.”