In the primary analysis of the Lung Cancer Mutation Consortium 3 (LCMC3) study, neoadjuvant atezolizumab monotherapy was well tolerated and "successfully met its primary endpoint of achieving major pathologic response" in 21% of patients, Dr. Jay Lee said during a press briefing at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer.
Following neoadjuvant atezolizumab, surgery was performed with "low perioperative morbidity and mortality, usually within a narrow protocol window and with a short time frame from completion of atezolizumab and with a correspondingly high complete resection rate," reported Dr. Lee, chief of the Division of Thoracic Surgery at Ronald Reagan UCLA Medical Center in Los Angeles.
Atezolizumab is a PD-L1 inhibitor approved last year in the United States for first-line treatment of adults with metastatic NSCLC.
The LCMC3 study included 181 patients (median age, 65 years; 51% women) with stage-IB to -IIIB NSCLC (62% with nonsquamous histology) and no EGR or ALK mutations. Patients were treated with 1,200 mg of atezolizumab intravenously every three weeks for up to two cycles followed by surgery performed between 30 and 50 days from the first cycle. Patients could continue atezolizumab for up to one year.
The primary endpoint of the study was major pathologic response, defined as less than or equal to 10% viable tumor cells at the time of surgery. Eighty-eight percent of patients underwent surgical resection and 144 (80%) made up the primary efficacy population.
Thirty of the 144 patients (21%) had a major pathologic response and 7% had a pathologic complete response.
Among 155 patients (four did not have a pathologic-stage evaluation), neoadjuvant atezolizumab led to tumor downstaging in 66 patients (43%) and upstaging in 29 (19%), Dr. Lee reported.
Overall, 140 of 159 patients (88%) underwent surgical resection within a median of 22 days (range, 11-74) after completing atezolizumab therapy.
Dr. Lee noted that surgery was performed with a minimally invasive approach - robotic or video-assisted thoracoscopic surgery (VATS) - in most patients, and "remarkably," only 15% required conversion to open thoracotomy. Most patients (145/159, 92%) had complete (R0) resection and intraoperative complications were rare (5/159, 3%).
In exploratory analyses, one-year disease-free survival was 85% in stage-IB to -IIIB disease, 92% for stage-IB to -IIB disease and 95% in stage IIIB disease.
"The study provides additional clinical evidence for the ongoing placebo-controlled phase III IMpower030 study of atezolizumab combined with platinum-based chemotherapy," Dr. Lee said.
The LCMC3 study was sponsored by Genentech. Dr. Lee disclosed financial ties to the company.
SOURCE: https://wclc2020.iaslc.org/ IASLC World Conference on Lung Cancer, held January 28-31, 2021.
By Megan Brooks
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