Herbst Highlights Link Between Biomarkers and Improved OS With Atezolizumab in NSCLC

Roy Herbst, MD, PhD

Initial findings from the phase III IMpower110 study showed that frontline atezolizumab (Tecentriq) extended overall survival (OS) compared with platinum-based chemotherapy in patients with advanced non—small cell lung cancer (NSCLC) who have high PD-L1 expression, said Roy S. Herbst, MD, PhD.¹

Moreover, an interim analysis of the trial, which was presented at the 2019 ESMO Immuno-Oncology Congress, showed that atezolizumab demonstrated superior OS benefit versus chemotherapy in patients with high PD-L1 expression across 3 separate immunohistochemistry (IHC) assays, as well as high blood tumor mutational burden (bTMB) for this patient population.²

PD-L1—high expression was defined as tumor cell (TC)3 or immune cell (IC)3 by Ventana SP142 staining, ≥50% tumor proportion score by Dako22C3 staining, and TC ≥50% by Ventana SP263 staining.

The median OS for atezolizumab compared with chemotherapy was 20.2 months and 13.1 months, respectively, by Ventana SP142 staining (HR, 0.59; 95% CI, 0.40-0.89), 20.2 months versus 11.0 months, respectively (HR, 0.60; 95% CI, 0.41-0.86) via Dako22C3, and 19.5 months versus 16.1 months, respectively (HR, 0.71; 95% CI, 0.50-1.00) via Ventana SP263.

Finally, patients with bTMB ≥10 mutations/megabase had a median OS of 11.2 months when treated with atezolizumab versus 10.3 months in those who received chemotherapy (HR, 0.87; 95% CI, 0.58-1.30).

"With all of the focus on blueprint studies and biomarkers, IMpower110 shows the ability to look across biomarkers to understand who benefits or not, and why," said Herbst, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital. "These are very promising results that will add to the use of these drugs in the field. I am happy to have been a part of it."

In an interview with OncLive^®, Herbst, who is also the Ensign Professor of Medicine and professor of pharmacology, and the associate cancer center director for translational research at the Yale Cancer Center, discussed the implication of the IMpower110 results in advanced NSCLC.

OncLive: Could you discuss the results that were first presented at the 2019 ESMO Congress?

Herbst: The topline data showed that in the group of patients who were TC3/IC3 high—meaning that they either had ≥50% of the TCs positive or ≥10% of the ICs positive—atezolizumab improved survival versus chemotherapy in this setting.

These were quite promising results, and atezolizumab is the first PD-L1 inhibitor to be introduced to this setting.

What was the activity observed in various biomarker subgroups, which was presented at the 2019 ESMO Immuno-Oncology Congress?

We are seeing a trend toward improvement with atezolizumab over chemotherapy in all of the biomarker subgroups. We looked at it for [Ventana] SP142, as well as [Ventana] SP263 and Dako22C3. Across the spectrum of biomarkers, [an OS improvement was shown].

What was observed regarding bTMB?

bTMB showed that there was a strong trend for PFS when you use bTMB >16 mutations/megabase. There was a very strong improvement in outcomes, suggesting that bTMB could be used as a marker [for response to immunotherapy].

Also, there was a strong trend for improved survival. It was only a trend though, and was not statistically significant.

Do these findings have clinical implications that could influence how you treat patients in practice?

Yes, they do. This could have huge implications for clinical practice. If a regulatory approval occurs, it will make atezolizumab a potential frontline therapy that could be used for patients with NSCLC.

Of course, the beautiful thing is that [an approval] would allow for combinations of atezolizumab. You can imagine the multitude of combinations with a PD-L1 inhibitor that could move [the field] forward.

If frontline atezolizumab monotherapy is approved in this indication, what factors would you consider in determining first-line treatment for a patient?

I would of course use it for patients who are TC3/IC3 [high]. Given the other biomarkers, and again pending regulatory approval, I would also use it as an alternative to pembrolizumab (Keytruda) in patients who were PD-L1 high by the 22C3 marker.

We now have a second drug that has confirmed the single-agent use of immunotherapy in the frontline setting for NSCLC, both squamous and nonsquamous histology. That is very important. Of course, the combinations that we make with this are going to be quite important as well.

I am very excited about these results. It is paradigm changing, and it will have great importance in the clinic to give another option for patients with advanced NSCLC.

References

1. Spigel DR, De Marinis F, Giaccone G, et al. IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1—selected NSCLC. Ann Oncol. 2019;30(suppl_5):v851-v934. doi: 10.1093/annonc/mdz394.
2. Herbst RS, Marinis FD, Giaccone G, et al. Clinical efficacy of atezolizumab in biomarker subgroups by SP142, SP263 and 22C3 PD-L1 immunohistochemistry assays and by blood tumour mutational burden: results from the IMpower110 study. Ann Oncol. 2019;30(suppl_11):mdz453. doi: 10.1093/annonc/mdz453.