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29-05-2019 | Oncology | News | Article

First-line atezolizumab–chemotherapy an option for nonmutated metastatic NSCLC

medwireNews: Patients with treatment-naïve, nonmutated, nonsquamous, advanced non-small-cell lung cancer (NSCLC) derive a significant survival benefit from the addition of the PD-L1 inhibitor atezolizumab to chemotherapy, indicate phase III trial findings.

“The results from IMpower130 suggest that atezolizumab plus chemotherapy is an additional first-line treatment option to be considered when formulating treatment plans” for this patient population, say the investigators.

Speaking to medwireNews, lead author Howard (Jack) West (City of Hope Comprehensive Cancer Center, Duarte, California, USA) commented that “IMpower130 is now on a very short list of trials in advanced NSCLC that has demonstrated not only a significant improvement in progression-free survival but also a significant improvement in overall survival, despite the majority of patients assigned to initial chemotherapy alone crossing over to subsequent immunotherapy.”

He added: “The trial offers a compelling alternative regimen to the available standards of care, one that is particularly welcome for the subgroup of patients who cannot tolerate pemetrexed or steroids that are routinely administered with it.”

As reported in The Lancet Oncology, the study included 723 participants who had not previously received chemotherapy for stage IV disease, but individuals with EGFR or ALK alterations were required to have progression or intolerance to at least one prior tyrosine kinase inhibitor.

The co-primary endpoint of overall survival in the EGFR or ALK wild-type population (n=679) was a median of 18.6 months for patients who received atezolizumab 1200 mg every 3 weeks alongside carboplatin (area under the curve 6 mg/mL per min every 3 weeks) and nab-paclitaxel (100 mg/m2 weekly) for four or six cycles of 21 days.

This was significantly longer than the median of 13.9 months observed for the participants who received just chemotherapy on the same schedule, and equated to a significant 21% reduced risk for death with the combination.

“The magnitude of overall survival benefit in reduction of the risk of death and median improvement of 4.7 months is clinically meaningful as well as significant,” the researchers emphasize.

The combination of atezolizumab and chemotherapy was likewise associated with a significant prolongation of the other primary endpoint of progression-free survival, at a median of 7.0 months compared with 5.5 months for chemotherapy alone, resulting in a 36% reduction in the risk for progression or death.

The findings were similar in the overall intention-to-treat population, and subgroup analysis also pointed to an overall and progression-free survival benefit of atezolizumab across most subgroups. The only exceptions were patients with liver metastases and those with EGFR or ALK alterations.

West noted that the inclusion of these patients with EGFR- or ALK-mutated disease “provides helpful insight that the benefit seen in this subset of patients on the IMpower150 trial with the combination of carboplatin, paclitaxel, bevacizumab, and atezolizumab may be related to the inclusion of bevacizumab, which was not included in IMpower130.”

“The safety profile of atezolizumab plus chemotherapy was consistent with the known adverse events related to single-agent therapy” and there were no new safety signals, report the researchers.

Treatment-related adverse events (AEs) of grade 3 or 4 occurred in 73% of participants in the combination group and 60% of those in the chemotherapy group, while the corresponding rates of treatment-related serious AEs were 24% and 13%. Eight deaths in the atezolizumab plus chemotherapy arm were attributed to the treatment, as was one death in the chemotherapy arm.

The authors of an accompanying commentary say that this trial and KEYNOTE-189, which investigated the addition of the PD-1 inhibitor pembrolizumab to chemotherapy, “seem to have established the new standard care of first-line treatment for advanced non-squamous non-small-cell lung cancer.”

But they note that unanswered questions remain, such as “how to select a treatment regimen in clinical practice.”

Yangqiu Li (Jinan University, Guangzhou, China) and Yi-Long Wu (Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, Guangzhou) continue: “Perhaps new head-to-head trials of different anti-PD-1 or anti-PD-L1 agents are needed, even though they might not be commercially driven.”

By Shreeya Nanda

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

Lancet Oncol 2019; doi:10.1016/S1470-2045(19)30167-6
Lancet Oncol 2019; doi: 10.1016/S1470-2045(19)30148-2

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