Adjuvant atezolizumab extends DFS in early-stage NSCLC
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Atezolizumab after surgery and chemotherapy reduced risk for disease recurrence or death among patients with stage II to stage IIIA non-small cell lung cancer, according to research presented during the virtual ASCO Annual Meeting.
Patients with tumors that expressed PD-L1 demonstrated a particularly pronounced DFS benefit with adjuvant atezolizumab (Tecentriq, Genentech) compared with best supportive care, results of the IMpower010 trial showed.
“This is the first immune checkpoint inhibitor to show a DFS benefit in a randomized, phase 3 trial in early-stage NSCLC,” Heather A. Wakelee, MD, thoracic specialist, professor of medicine and chief of the division of oncology at Stanford University Medical Center, told Healio.
“Despite dramatic improvements in treatment for advanced-stage NSCLC, including targeted therapy and immune therapy, little progress has been made in treating early-stage lung cancer since the positive chemotherapy trials 15 years ago,” she added. “EGFR-targeted therapy can improve DFS for patients with tumors with EGFR mutations, but the vast majority of patients have no option other than chemotherapy. We hoped that the use of atezolizumab would improve outcomes for patients with early-stage NSCLC as it has for those with advanced-stage NSCLC.”
Wakelee and colleagues enrolled 1,280 patients with stage IB to stage IIIA NSCLC and an ECOG performance status of 0 to 1 who underwent complete resection 4 to 12 weeks prior to enrollment. Of them, 1,269 received up to four 21-day cycles of cisplatin-based chemotherapy with pemetrexed, docetaxel, gemcitabine or vinorelbine. Following chemotherapy, researchers randomly assigned 1,005 patients 1:1 to 16 cycles of 1,200 mg atezolizumab every 3 weeks or best supportive care.
Researchers evaluated DFS, the study's primary endpoint, and OS, the study's secondary endpoint, hierarchically: first, DFS among patients with stage II to stage III disease and PD-L1 expression on at least 1% of tumor cells (atezolizumab, n = 248; best supportive care, n = 228); second, DFS among patients with stage II to stage IIIA disease (atezolizumab, n = 442; best supportive care, n = 440); third, DFS among the intent-to-treat population (atezolizumab, n = 507; best supportive care, n = 498); and last, OS among the intent-to-treat population.
Median follow-up was 32.8 months (range, 0.1-57.5) in the intent-to-treat population.
The results showed atezolizumab, when compared with best supportive care, reduced the risk for recurrence or death by 34% among patients with stage II to stage IIIA disease whose tumors had PD-L1 expression of at least 1% (median DFS, not evaluable vs. 35.3 months; HR = 0.66; 95% CI, 0.5-0.88).
Among all patients with stage II to stage IIIA disease, atezolizumab reduced the risk for recurrence or death by 21% vs. best supportive care (median DFS, 42.3 months vs. 35.3 months; HR = 0.79; 95% CI, 0.64-0.96). The difference in DFS among the intent-to-treat population had not crossed the boundary for statistical significance (median, not evaluable vs. 37.2 months).
OS data had not yet matured and had not been formally tested, Wakelee said.
“Atezolizumab given after surgery and chemotherapy has a more profound effect on DFS among patients with stage II to stage IIIA NSCLC with PD-L1-expressing tumors than the benefit seen with chemotherapy among all-comers in the trials 15 years ago,” Wakelee said. “PD-L1 expression should be examined in all patients after surgical resection with consideration for use of adjuvant atezolizumab — once it is approved in this setting — for patients with tumors that express PD-L1. Over 50% of resected tumors that were tested for PD-L1 expressed PD-L1, so this treatment may be an option for a large percentage of patients with resected early-stage NSCLC.”
Researchers identified no new safety signals, according to Wakelee. Grade 3 to grade 4 adverse events occurred among 21.8% of 495 patients who had at least one dose of atezolizumab and 11.5% of 495 patients in the best supportive care cohort who had at least one post-baseline assessment. Researchers discontinued treatment for 18.2% of patients in the atezolizumab group because of toxicity.
Wakelee said the study continues to examine OS and DFS among all enrolled patients, including those with stage IB NSCLC, who represent only 12% of patients on the trial.
“There [also] is ongoing work looking at using atezolizumab and other immune therapy prior to surgery,” Wakelee told Healio. “Biomarker testing is important to allow us to give optimal adjuvant therapy to patients. Biomarker testing includes looking for EGFR mutations and now also for PD-L1 expression.”
Perspective
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Bing Xia, MD
This is very exciting data that, in my opinion, will change clinical practice.
Even in early-stage lung cancer, we see quite a few patients with disease recurrence, so anything we can do to improve DFS, we should definitely do for patients. Because this study shows that atezolizumab improves DFS, adding atezolizumab in stage II to stage IIIA disease can hopefully decrease the number of patients we see with disease recurrence.
Although biomarker testing has traditionally been done in late-stage disease — specifically stage IV metastatic disease — both this study and the ADAURA trial are establishing a role for biomarker testing in earlier-stage disease.
For the most part, in my experience, immunotherapy such as atezolizumab is pretty well-tolerated. The patients in this study who had to discontinue atezolizumab due to toxicity definitely will need to be monitored.
Perspective
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Fred R. Hirsch, MD, PhD, FASCO
This is an important study showing that DFS was significantly prolonged by adding immunotherapy to chemotherapy for adjuvant therapy of resected stage II to stage IIIA NSCLC. This study clearly emphasized the role of immunotherapy in early-stage NSCLC and moves immunotherapy earlier and earlier in the treatment scenario for patients with NSCLC. Of course, OS data are not yet mature, which is crucial for this stage of disease, but it is expected that these results will translate into better OS. We have not yet seen data from stage IB (> 4 cm) or patients with negative PD-L1.
Mount Sinai's Tisch Cancer Institute
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Wakelee HA, et al. Abstract 8500. Scheduled for presentation at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
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