Immunotherapy has already had a major impact on the treatment of patients with later stages of non-small cell lung cancer (NSCLC): New clinical data now show benefits in patients with early-stage disease.
Patients with NSCLC in phase IB-IIIA showed significantly improved disease-free survival (DFS) when atezolizumab (Tecentriq) was added to adjuvant chemotherapy after resection, according to the results of an interim analysis of the IMpower010 to study.
It should be noted that the benefit with atezolizumab compared to better supportive care was greater in patients with programmed death ligand 1 (PD-L1) expression in their tumor, in whom the improvement in DFS was a significant 34%.
This is the “first global phase III trial that uses an immune checkpoint inhibitor to show a disease-free survival outcome in the early phase of NSCLC,” said lead researcher Heather Wakelee, MD, professor of medicine and head of the Oncology Division at Stanford University Medical Center, Stanford, California.
He was speaking at a press conference ahead of next month’s annual meeting of the American Society of Clinical Oncology, where the results will be presented on June 6th.
Wakelee added that “the planned analysis for disease-free survival and overall survival in the populations intending to treat will continue with long-term follow-up.”
Asked if the drug could be recommended for these patients based on current results, Wakelee said we “obviously need approval” for this use from the U.S. Food and Drug Administration, but added that “the FDA has approved other agents, especially most recently osimertinib [Tagrisso], based on a disease – free survival endpoint “.
These new results show that the advantage with atezolizumab plus chemotherapy is “deeper” than with chemotherapy plus the best supportive care “and therefore for me it would be something I would like to offer my patients in this environment.” .
Wakelee also stressed the importance of lung cancer screening, so the disease is detected in earlier stages “when it is potentially curable.”
He also stressed the importance of seeking biomarker testing for patients with resected disease EGFR mutations, which can be treated with EGK TKIs and also, at some point, to check for PD-L1 … because, in this trial, the vast majority of the benefits “appeared to be in those with PD-L1 expression in their tumors.
Julie R. Gralow, MD, medical director and executive vice president of ASCO, said “immune checkpoint inhibitors have certainly changed the treatment landscape for many types of cancer” and the current study “is the the first time we see immunotherapy that is effective in the treatment of early stage NSCLC. “
“This is a major breakthrough in understanding the role of immunotherapy in early-stage lung cancer” and “potentially a step forward for many patients.”
Details of the study
Wakelee has commented that the standard of care for many patients with NSCLC in phase IB-IIIA “has not changed for many years,” although “significant progress” has been made in the treatment of more advanced diseases.
Consequently, most patients with resected NSCLC continue to receive platinum-based adjuvant chemotherapy, which has been shown to reduce the risk of disease recurrence by 16% in those with completely resected disease.
The new study aims to examine the benefit of adding atezolizumab to adjuvant chemotherapy in global phase III Study IMpower010.
Patients had to have phase-IBC IIIA NSCLC, with phase IB tumors ≥ 4 cm in size and tumor tissue available for PD-L1 analysis. After complete resection, 1280 patients received up to four cycles of platinum-based adjuvant chemotherapy.
Of these, 1005 patients were randomly assigned 1: 1 to receive 16 cycles of atezolizumab 1200 mg IV every 3 weeks or the best supportive care.
Provisional results show that, after a mean follow-up of 32.8 months, the addition of azolizumab significantly reduced the risk of recurrence or death versus better supportive care in patients whose tumors had an expression of PD-L1 ≥1%, with a risk ratio of 0.66 (Pg = .004).
At 24 months, the DFS rate was 74.6% among patients with atezolizumab and 61% in those receiving the best supportive care, down to 60% and 48.2%, respectively, at 36%. months.
When all randomized patients were examined, the addition of azolizumab was associated with a lower reduction in the risk of recurrence of death compared with better supportive care, with a risk ratio of 0.79 after an average follow-up of 32.2 months (Pg = 0.02).
According to the intention to treat the analysis, the reduction of the risk of recurrence or death with atezolizumab was of limit importance, with a risk ratio of 0.81 after a mean follow-up of 32.2 months (Pg = 0.04).
Wakelee noted that patients with stage IB disease, who accounted for about 12% of those participating in the trial, “usually do better and need more time to see some of the results of the recurrence of the disease. “, so these results are” preliminary “.
He also stressed that the overall survival data are not yet mature and that survival was not formally verified in the current analysis.
In terms of safety, the profile of adverse events with atezolizumab was consistent with previous reports, the researchers noted in the summary. However, Wakelee said at the conference that “we had to stop treatment with atezolizumab in 18% of patients because of toxicity.”
Adverse events of all grades were reported in 70.7% of the best supportive care group compared to 92.7% among those receiving atezolizumab, while adverse events of grade 3-4 were reported in 11.5% and 21.8% of patients, respectively.
The study was funded by Hoffmann-LaRoche.
Wakelee reports relationships with AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Helsinn Therapeutics, Janssen Oncology, Mirati Therapeutics, Xcovery, ACEA Biosciences (Inst), Arrys Therapeutics (Inst), AstraZeneca / MedImmune (Inst), Bristol-Myers Squibb (Inst) , Celgene (Inst), Clovis Oncology (Inst), Exelixis (Inst), Genentech / Roche (Inst), Gilead Sciences (Inst), Merck (Inst), Novartis (Inst), Pharmacyclics (Inst), Seattle Genetics (Inst) , and Xcovery (Inst). It also reports uncompensated relationships with Genentech / Roche, Merck and Takeda.
Gralow reports relationships with AstraZeneca, Genentech, Sandoz and Immunomedics.
Annual Meeting of the American Society of Clinical Oncology: Summary 8500. It will be presented on June 6, 2021.
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