Atezolizumab-chemo confers durable survival benefit in ES-SCLC

In the merged analysis of the IMpower133 trial and IMbrella A open-label extension study, the combination of the PD-L1 inhibitor atezolizumab and a chemotherapy regimen comprising carboplatin and etoposide (CP/ET) demonstrated potential for survival benefit of up to 5 years in patients with extensive stage-small-cell lung cancer (ES-SCLC).

“SCLC is an aggressive and exceptionally lethal subtype of lung cancer characterized by rapid growth and early spread,” said Dr Stephen Liu from the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, US, at WCLC 2023.

For nearly 4 decades, platinum-etoposide chemo was the historic standard of care (SoC) for ES-SCLC. However, initial response rates, albeit high, were transient, Liu stressed. “Immunotherapy changed this and revolutionized the ES-SCLC treatment landscape. In Impower133, the addition of atezolizumab improved survival in ES-SCLC, changing the SoC and leading to its approval in >100 countries around the world.”

“With no 5-year survival data yet reported for first-line immunotherapy in SCLC … [our] data provide the first report of survival outcomes for patients who received first-line immunotherapy with chemotherapy for ES-SCLC,” he continued.

In IMpower133, 403 patients with untreated ES-SCLC were randomized 1:1 to receive four cycles of standard CP/ET with atezolizumab or placebo in the induction phase. Participants continued atezolizumab or placebo during the maintenance phase. IMbrella A comprised patients from atezolizumab trials (including IMpower133) who were continuing atezolizumab at the time of study closure or were in survival follow-up. Eighteen patients (median age 60.5 years, 61 percent male) from the IMpower133 experimental arm rolled over to IMbrella A; those in the control arm were ineligible to roll over. [WCLC 2023, abstract OA01.04]

“[With atezolizumab-chemo,] we saw a 3-year overall survival (OS) rate of 16 percent, a 4-year OS rate of 13 percent, and a 5-year OS rate of 12 percent, suggesting a plateau of the survival curve and a tail,” said Liu.

All IMpower133 patients who rolled over to IMbrella A achieved either a complete or partial response.

Of the 11 patients who were alive and who remained on study for 5 years (median age at baseline 59 years), six continued receiving atezolizumab. Four had ECOG PS 1, two had baseline brain metastases, and none had baseline liver metastases.

In IMbrella A, only serious adverse events (SAEs) and AEs of special interest (AESI) were collected. Three patients had a SAE. Only one AESI was identified (grade 2 hypothyroidism), which did not interfere with atezolizumab treatment, noted Liu.

“Considering the low incidence of SAEs and AESI, the long-term safety profile of atezolizumab-chemotherapy is encouraging. Late onset immune-mediated toxicities were rare and manageable. The final safety analysis aligned with the primary analysis with no safety signals observed,” he said.

Better numbers than before

“[The current findings showed that] 5-year survival can be achieved with immunotherapy in SCLC. This is a very important result because for the very first time, we have 5-year survival results for [ES-SCLC] patients treated with atezolizumab,” said discussant Dr Noemí Reguart from Hospital Clínic Barcelona, Spain.

Despite the limited patient numbers, the current OS data compare favourably with the historic 5-year OS rate with chemo alone, which is about 2 percent, said Liu. “While the numbers are not what we wanted, it is better than what we once had.”

“The 12-percent OS rate is encouraging but we need to improve this result,” said Reguart. Given the lack of data beyond this point, Reguart called for more follow-ups to see if the survival curves can be maintained and to ascertain the magnitude of benefit of atezolizumab plus CP/ET chemotherapy.