The latest analysis from the IMpower133 trial has demonstrated continued improvement in outcomes for patients with extensive-stage small cell lung cancer ( ES-SCLC ) who received monotherapy with Atezolizumab ( Tecentriq ) after initial treatment consisting of chemotherapy with or without Atezolizumab.

Atezolizumab is a monoclonal antibody against programmed cell death-ligand 1 ( PD-L1 ). In the phase I/II IMpower133 trial, ES-SCLC patients received four 21-day cycles of Carboplatin and Etoposide with either Atezolizumab or placebo, followed by maintenance Atezolizumab or placebo.Treatment continued until progressive disease or loss of clinical benefit.
The trial has demonstrated that adding Atezolizumab to chemotherapy resulted in significantly longer overall survival ( OS ) and progression-free survival ( PFS ) than chemotherapy alone.

The current study was an exploratory analysis assessing the benefit of Atezolizumab versus placebo maintenance therapy among 318 patients who received at least one dose of maintenance therapy ( 154 in the Atezolizumab arm and 164 in the placebo arm ).
The groups were comparable in terms of median age ( 64 vs 63 years ), sex ( both 65% male ), Eastern Cooperative Oncology Group performance status ( ECOG PS ), current or previous tobacco use, prevalence of 3 or more metastasis sites, presence of brain metastases, and treatment with four cycles of Carboplatin and Etoposide.
The two primary endpoints were overall survival and progression-free survival, which were computed from the start of the maintenance treatment.

Significant predictors for reaching the maintenance phase included ECOG PS ( odds ratio, OR=0.439; P = 0.004 ), lactate dehydrogenase level ( OR=0.589; P = 0.053 ), and age ( OR=0.459; P = 0.001 ).
Age had a significant interaction with treatment ( P = 0.004 ).

The dose was modified or interrupted in 30 ( 19% ) patients in the Atezolizumab arm and in 17 ( 10% ) patients in the placebo arm.

Median overall survival in the maintenance population was longer for the 154 patients treated with Atezolizumab, compared with the 164 patients in the placebo arm ( 15.7 vs 11.3 months; hazard ratio, HR=0.59, 95% confidence interval 0.43–0.81, P = 0.008 ).
Median progression-free survival for the maintenance population was 5.5 months for the Atezolizumab arm and 4.5 months for the placebo arm ( HR=0.64, 95% CI 0.50–0.82; P = 0.008 ).

The survival benefit associated with Atezolizumab was retained after adjusting for baseline characteristics, which included ECOG PS, sex, age, presence of brain metastases, lactate dehydrogenase level, sum of longest diameters of target lesions, and number of metastatic sites, for both overall survival ( hazard ratio, HR=0.59, 95% CI, 0.43–0.81; P = 0.001 ) and progression-free survival ( HR=0.64, 95% CI, 0.50–0.82; P less than or equal to 0.001 ).

No new or unexpected safety signals were evident. Safety results were comparable between treatment arms, despite the continuation of Atezolizumab monotherapy in the maintenance phase.
In the maintenance population, grade 3/4 adverse events occurred in 28% of patients in the Atezolizumab arm and 23% in the placebo arm. The respective rates of serious adverse events were 15% and 12%.

Immune-related adverse events were more frequent in the Atezolizumab arm, compared with the placebo arm ( 26% vs 15% ).
Grade 3/4 rash occurred in 2 patients in the Atezolizumab arm and 1 patient in the placebo arm.
There was one case each of grade 3/4 pneumonitis in each study arm.
There were 2 cases each of grade 3/4 pneumonitis and pancreatitis in the placebo arm; there were 2 and no cases, respectively, in the Atezolizumab arm.

In conclusion, both induction treatment with Atezolizumab plus Carboplatin and Etoposide as well as maintenance treatment with Atezolizumab appear to contribute to the overall survival benefit observed in IMpower133. ( Xagena )

Source: 2020 ( International Association for the Study of Lung Cancer’s World Conference on Lung Cancer ) IASCL - WCLC Virtual Meeting, 2021

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