Abstract
In mid-March, the FDA approved the PD-L1 inhibitor atezolizumab in combination with carboplatin and etoposide as a first-line therapy for small cell lung cancer. The approval was based on results from the phase III IMpower133 trial in which adding atezolizumab to chemotherapy extended overall and progression-free survival.
In mid-March, the FDA approved the PD-L1 inhibitor atezolizumab (Tecentriq; Roche) in combination with carboplatin and etoposide as a first-line therapy for small cell lung cancer (SCLC), making it the first immunotherapy approved for patients just diagnosed with the disease. The decision was based on results of the phase III IMpower133 trial (N Engl J Med 2018;379:2220–9).
Mechanism of action of atezolizumab. (Modification of figure originally published in Inman BA, Longo TA, Ramalingam S, Harrison MR, Clin Cancer Res 2017;23:1886–90)
“This is the first approval in a very long time for first-line treatment of small cell lung cancer—this is a patient population that has been in great need of new therapeutic options,” says Charles Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York, NY. “It is a very aggressive disease, and these patients have a very poor prognosis, so any steps forward are certainly welcome,” Rudin says.
In the IMpower133 trial, atezolizumab plus standard carboplatin and etoposide chemotherapy extended median overall survival by 2 months and median progression-free survival by 0.9 months compared with a placebo plus chemotherapy—statistically significant differences.
Although atezolizumab offers only a modest survival gain, Rudin says it is becoming the first-line standard of care. “It's already been fairly widely adopted” since publication of the results, he says, and has been incorporated into the National Comprehensive Cancer Network treatment guidelines.
However, “the potentially transformative benefit of immunotherapy isn't really the change to the median” survival, says Rudin, but the durable responses it might elicit in a small number of patients. At MSKCC, for example, rare patients with SCLC have benefited from it for several years. Thus, “most patients will want to get it, and most oncologists will want to give patients the opportunity to get it,” he says.
Further research should test whether adding other agents to maintenance immune checkpoint inhibitors can improve their efficacy and increase the number of patients who derive a long-term benefit, Rudin says. “This approval is a landmark for small cell lung cancer therapy, but the reality is we need a lot more advances like this to really make a difference.” –Catherine Caruso
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