Similar survival outcomes of a real-world study of a first-line treatment regimen were demonstrated in the phase 3 IMpower133 trial. The study, IFCT 1905-CLINATEZO, assessed the safety and effectiveness of chemotherapy plus atezolizumab in patients with small cell lung cancer (SCLC). The findings of IFCT 1905-CLINATEZO were presented by Lionel Falchero, MD, at the ASCO Annual Meeting 2023, held June 2-6, in Chicago.
“The data [of IFCT 1905-CLINATEZO] demonstrate the reproducibility of the findings of the Impower133 trial in the real-world,” says study co-author Nicolas Girard, MD, PhD. “In addition, the prognostic factors we observed appear to be different than the ones reported in the IMpower133 trial. Notably, we can see that, even in the setting of second-line treatment, more than half of the patients will gain control of the disease. This has always been a major challenge in SCLC.”
The IFCT 1905-CLINATEZO study included 1,402 patients with extensive-stage SCLC who were treated with the combination regimen of chemotherapy and atezolizumab; subsequent treatment sequences were also examined.
Most Patients Achieved Partial Response
At ASCO, Dr. Falchero and colleagues reported the findings from 518 patients who received chemotherapy plus atezolizumab between May 2019 and January 2020. Most of this population was male (66%), and the mean age was 65.7. Brain metastases were observed in 27% of the patients, and 89% had a performance status of 0 or 1. A minority of the patients had received at least one previous treatment (10.6%). The median number of received atezolizumab injections was seven, and the median duration of treatment was 4.9 months.
A complete response was reached by 3.9% of study patients, and a partial response was achieved by 77.1% of patients; 10.2% had stable disease. The patients were followed for a median duration of 30.8 months, after which a median overall survival (OS) of 11.3 months was reported. The corresponding 12-month and 24-month OS rates were 46.7% and 21.2%, respectively. The median OS in patients who had received a prior therapy appeared to be somewhat higher, at 14.9 months. The median progression-free survival time was 5.2 months. Most patients received subsequent therapy (66.4%).
Relatively Slight Increase Was Observed in Median Overall Survival
“The IMpower133 trial is a placebo-controlled phase 3 trial that compared a combination of atezolizumab plus standard of care chemotherapy with platinum etoposide to four cycles of immunotherapy plus chemotherapy, followed by maintenance with atezolizumab alone, is a very new concept in this disease,” Dr. Girard says.
He notes that the number of chemotherapy cycles is reduced, whereas maintenance therapy with immunotherapy is being introduced in the management of extensive-stage SCLC. “The trial demonstrated survival benefits with the addition of immunotherapy to chemotherapy in this setting,” Dr. Girard continues. “Patients moved from a median OS of 10 months with chemotherapy alone to 12 months with the addition of atezolizumab.”
A relatively slight increase in median OS is seen, he adds, but there are long-term survivors as well. “This is something we did not see with chemotherapy alone.”
As Dr. Girard and colleagues observe, more than one-quarter of the study patients had brain metastases, which represents a real-world challenge.
“[For] patients with brain metastasis to be eligible to be enrolled in clinical trials, they should have no symptoms,” explains Dr. Girard. “In a real-world setting, you are obviously treating some patients with larger brain metastases and patients who have symptoms from their brain metastases. It is interesting to see that we have a high number of patients with brain metastases, because this [reflects] the real-world situation. On the other hand, approximately 90% of the patients in our study had a [satisfactory] performance status, just like patients who are included in clinical trials.” However, Dr. Girard clarifies that this can be explained by the efficacy of immunotherapy. “We know that immunotherapy beyond a performance status of 1 has limited efficacy,” he says.
These Data Can Help Researchers Answer Key Questions
Additionally, a significant proportion of patients had radiotherapy during the induction treatment with immunotherapy and chemotherapy. “This is actually one of the key learnings of this study,” says Dr. Girard. “It mostly comprised palliative intent radiotherapy on bone metastases, but also whole brain irradiation. Furthermore, some patients received thoracic radiotherapy in the context of a significant or major partial response.” Going forward, Dr. Girard and colleagues seek to answer important questions. “We are [now] able to deliver descriptives of the subsequent treatments that were administered to patients,” says Dr. Girard. “This information was not analyzed in the clinical trial. These data can help us answer such questions as, ‘What should we do with patients who have disease progression? Can we rechallenge these patients? And what should we do with immunotherapy at this point? Should we maintain or discontinue immunotherapy?’”
