Atezolizumab plus chemotherapy improves PFS in non-small cell lung cancer

Mark A. Socinski

CHICAGO — The addition of atezolizumab to bevacizumab plus chemotherapy extended PFS for patients with non-small cell lung cancer, according to results from the IMpower150 study presented at American Association for Cancer Research Annual Meeting.

Perspective from Edwin Yau, MD, PhD

Researchers observed increased PFS regardless of tumor PD-L1 expression, as well as among those with EGFR or ALK genomic alterations and those with liver metastases.

“Atezolizumab [Tecentriq, Genentech] is an anti-PD-L1 antibody that blocks the binding of PD-L1 to its receptors PD-1 and B7, thus restoring tumor-specific immunity,” Mark A. Socinski, MD, executive medical director of Florida Hospital Cancer Institute, said during his presentation. “Atezolizumab has demonstrated OS benefit and is approved in the United States and Europe for the treatment of NSCLC in the in the second-line setting and beyond, regardless of PD-L1 expression.”

In the IMpower 150 study, Socinski and colleagues assessed the addition of atezolizumab in the first-line setting for 692 patients with nonsquamous NSCLC.

Patients received either 1,200 mg of atezolizumab plus 15 mg/kg of bevacizumab (Avastin, Genentech), carboplatin and paclitaxel, or a control regimen of bevacizumab plus carboplatin and paclitaxel.

Researchers reported longer median PFS in the experimental arm (8.3 months vs. 6.8 months) across all PD-L1 expression subgroups, including patients with PD-L1 expression of less than 1% or from 1% to 50% (HR = 0.62; 95% CI, 0.5-0.76).

For patients with PD-L1-low tumors, defined as those with expression between 1% and 50% (n = 140), median PFS was 9.7 months for those assigned atezolizumab and 6.9 months for those assigned the control regimen (HR = 0.57; 95% CI, 0.38-0.84). Researchers observed a similar among patients with PD-L1 expression of 50% or higher (9.1 months vs. 6.2 months; HR = 0.5; 95% CI, 0.33-0.77).

PFS in the experimental study arm was similar regardless of whether the SP142 assay or SP263 assay was used for patients with PD-L1 expression of:

At least 50% (HR = 0.49; 95% CI, 0.3-0.79 vs. HR = 0.5; 95% CI, 0.33-0.77);

1% to 50% (HR = 0.53; 95% CI, 0.37-0.76 vs. HR = 0.57; 95% CI, 0.38-0.84); and

Less than 1% (HR = 0.77; 95% CI 0.57-1.04 vs. HR = 0.72; 95% CI, 0.53-0.97).

Patients with EGFR exon 19 deletion of L858R (n = 59) achieved improved PFS with the addition of atezolizumab (10.2 months vs. 6.1 months; HR = 0.41; 95% CI, 0.22-0.78).

Additionally, researchers observed a PFS improvement among patients with liver metastases assigned to the experimental regimen (8.2 months vs. 5.4 months; HR = 0.4).

“Atezolizumab plus bevacizumab plus chemotherapy demonstrated significant PFS benefit in chemotherapy-naive nonsquamous NSCLC across all PD-L1 subgroups, regardless of the assay used. Clinically meaningful PFS benefit was observed in all patients, including those with EGFR mutations, ALK genomic rearrangements and liver metastases,” Socinski said. “These data suggest atezolizumab plus bevacizumab plus chemotherapy provides a new treatment option for these key patient populations.” – by Cassie Homer

References:

Kowanetz M, et al. Abstract CT076. Presented at American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.

Disclosures: Socinski reports grant support from Genentech. Please see the abstract for all other authors’ relevant financial disclosures.

Perspective

Edwin Yau, MD, PhD

This is a complicated study, but I think it offers some new insights. Researchers reported results of the arm that assessed the combination of the VEGF inhibitor and chemotherapy. We are eager to see the OS report that will be released later. However, PFS and response rate look exciting.

The most interesting thing about this study is that is gives us a first glimpse into the EGFR/ALK-mutant population, which has not seen a response to immunotherapy in any previous trial. Although this is a decent-sized trial, this subgroup is still a relatively small proportion of the patient population, so it is hard to draw definitive conclusions. However, at least it is the first signal we have seen of a response to immunotherapy in this patient population.

Going forward, it will be interesting to see the results of the arm without the VEGF inhibitor. This will tell us whether response in these EGFR-mutant and ALK-rearranged patients is similar with chemotherapy plus immunotherapy, or if it is the VEGF inhibitor plus immunotherapy that is key to this response.

We don’t know what kind of treatments these patients got before. We have to think about how this is going to affect our sequencing of therapies for these patients, who derive great benefit from tyrosine kinase inhibitors upfront. But, of course, we want to extend the long durable responses we see in immunotherapy to this patient population, and I think that is where the IMpower data are most intriguing.

Edwin Yau, MD, PhD

Roswell Park Comprehensive Cancer Center

Disclosures: Yau reports no relevant financial disclosures.