Adjuvant Atezolizumab Provides Potential Standard of Care for PD-L1+ NSCLC

In patients with stage II to IIIA non–small cell lung cancer (NSCLC), adjuvant atezolizumab (Tecentriq) led to improvement in disease-free survival (DFS) vs best supportive care following adjuvant chemotherapy, according to John V. Heymach, MD, PhD. He added that these results add to evidence that suggests adjuvant immunotherapy is likely to become the standard of care for patients with NSCLC.

Primary results of the phase 3 IMpower010 trial (NCT02486718) presented during the 2021 ASCO Annual Meeting reported a DFS hazard ratio (HR) of 0.79 (95% CI, 0.64-0.96) in the randomized population and an HR of 0.66 (95% CI, 0.50-0.88) in patients with PD-L1 expression of at least 1%.

“This is a landmark study because for the first time, we can say that adjuvant immunotherapy reduces the likelihood of recurrences in resected NSCLC,” Heymach said. “If you couple this with the earlier ADAURA studies that showed benefit for targeted therapies in the EGFR mutant population with osimertinib [Tagrisso], now for the first time…[it is apparent that] we're moving towards precision-guided therapies in the adjuvant setting.”

In an interview with OncLive^®, Heymach, chair of thoracic/head and neck medical oncology at The University of Texas, MD Anderson Cancer Center, discusses the background of the Impower010 trial, the benefit for patients with PD-L1 levels of at least 1%, and the exciting direction adjuvant therapy in NSCLC is heading.

OncLive^®: What served as the basis for this study?

Heymach: First, it's important to talk about the background. Historically, for patients who have surgically resected NSCLC, the standard of care is just chemotherapy. [Chemotherapy has] been the standard of care for decades now. That's changed recently for patients with EGFR mutations; the ADAURA study [NCT02511106] recently demonstrated that adjuvant osimertinib could provide benefit. But for the rest of patients with wild type EGFR, adjuvant chemotherapy remains the standard of care, despite the fact that we know immunotherapy adds tremendous benefit in the metastatic setting and the stage III setting. For the first time, in this study, we have clinical data in terms of [adverse] events [and] recurrence-free survival or disease-free survival for patients who've been treated with adjuvant immunotherapy.

From what we can see so far, the early results look quite strong. There [appears to be] a significant reduction in the likelihood of recurrences [with] adjuvant immunotherapy and the magnitude of that benefit appears to be quite substantial. To [provide a scale] of magnitude for that benefit, what we're seeing in this preliminary report is a hazard ratio of 0.66 for the initial group, the [patient population with] stage II to IIIA with PD-L1 greater than 1%. By comparison, adjuvant chemotherapy has a hazard ratio of 0.86. Whereas adjuvant chemotherapy reduces likelihood of recurrence by something like 14%, [in this study] we see a reduction in the likelihood of recurrence by [about] 34%. Putting this all together, I think this really suggests that in the near future, adjuvant immunotherapy is likely to become the standard. We're also waiting [for] the results of neoadjuvant immunotherapy which may [provide] additional benefit.

Which patient population benefits the most from adjuvant atezolizumab?

The benefit was most striking in [patients with a] PD-L1 greater than 1%, but there still appears to be a substantial benefit in the broader population, both in [those with] stage II to IIIA [disease and those] with any PD-L1 level in the intention to treat population that includes [patients with stages] IB to IIIA. The hazard ratio for the intention to treat [population], the largest group, was reported as 0.81. That's less benefit than the narrower group, the [PD-L1] greater than 1% group [in which] the hazard ratio is 0.66. However, 0.81 is still a substantial benefit. Adjuvant chemotherapy provides less benefit than the adjuvant immunotherapy does here, and it comes at the cost of greater toxicity.

We'll have to see what the FDA approval looks like assuming it does get approved. I would use it for all patients in the intention to treat analysis in the IB to IIIA with any PD-L [expression], assuming that the results hold up and show a similar trend in overall survival when those results come out.*

In terms of safety, did the toxicity seem to parallel what we know of immunotherapy in the metastatic setting?

There are no unexpected toxicities that were reported here. Adverse events leading to atezolizumab discontinuation happened in about 18% of patients [which is] a little bit higher than we'd [observe] with atezolizumab and monotherapy in the metastatic setting. [However], these patients are being treated for a longer period of time. In most cases, [patients] are already cured and as such, it's often harder to keep therapies going in the adjuvant setting, but there were no surprising safety signals. What we see reported for grade 5 toxicities is 0.8%, so less than 1%, obviously a small number of patients or just a couple patients. Given the potential likelihood of increasing cure rates, I think that's going to be a favorable risk-benefit ratio.

From a multidisciplinary approach to care, what would you say is the key takeaway from this trial?

We're going to start stratifying patients based on their genomic driver and potentially getting targeted therapies like osimertinib, or if they don't have a targetable mutation, then using immunotherapy in the adjuvant setting.

There are also promising results seen in the CheckMate 816 study [NCT02998528], [evaluating] neoadjuvant nivolumab and chemotherapy that was reported at the 2021 ASCO Annual Meeting. That wasn't recurrence-free or disease-free survival reported, that was just pathologic response rate, but we believe that also correlates with benefit.

We can see the space rapidly evolving and I think it's very exciting for lung cancer patients. There's going to be multiple choices in the near future of different types of adjuvant therapy to give including immunotherapy for those without driver alterations. I expect we're going to have traces of both neoadjuvant and adjuvant therapy, or just adjuvant therapy alone, when all these different [ongoing] phase 3 trials read out.

*Editor’s note: This interview was conducted prior to the October 15, 2021 FDA approval of atezolizumab for use as an adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non–small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on 1% or more of tumor cells, as determined by a FDA-approved test.

Reference

1. Wakelee HA, Altorki NK, Zhou C, et al. IMpower010: Primary results of a phase III global study of atezolizumab versus best supportive care after adjuvant chemotherapy in resected stage IB-IIIA non-small cell lung cancer (NSCLC). J Clin Oncol. 2021;39(15):8500. doi:10.1200/JCO.2021.39.15_suppl.8500