Neoadjuvant atezolizumab induces pathologic response in resectable NSCLC
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Neoadjuvant atezolizumab conferred a 21% major pathologic response rate among patients with resectable stage IB to stage IIIB non-small cell lung cancer.
Atezolizumab — a PD-L1 inhibitor that received FDA approval in 2020 for first-line treatment of adults with metastatic NSCLC — also appeared well-tolerated, according to findings presented during the virtual presidential symposium of the International Association for the Study of Lung Cancer World Conference on Lung Cancer.
“This study is unique in that it is the largest monotherapy checkpoint inhibitor study [among patients with resectable NSCLC],” Jay M. Lee, MD, chief of the division of thoracic surgery at Ronald Reagan UCLA Medical Center, said during his presentation. “Equally important was the aggressive collection of biospecimens that included tumor, lymph nodes and blood.”
The primary analysis of the Lung Cancer Mutation Consortium 3 (LCMC3) study included 181 patients (median age, 65.1 years; 51% women; 19% current smokers; 62% nonsquamous histology) with surgically resectable stage IB to stage IIIB NSCLC.
Patients received 1,200 mg atezolizumab (Tecentriq, Genentech) via IV every 3 weeks for up to two cycles followed by surgical resection and a 30-day post-surgery visit. Patients were permitted to continue adjuvant atezolizumab for up to 1 year.
Major pathologic response among those without EGFR or ALK mutations served as the primary endpoint. Exploratory endpoints included DFS and OS.
Among those without EGFR or ALK mutations, researchers reported a major pathologic response rate of 21% (95% CI, 14-28) and pathologic complete response rate of 7% (95% CI, 3-12).
“Forty-three percent of patients experienced downstaging after treatment with atezolizumab and, comparatively, 19% of patients experienced upstaging,” Lee said.
Overall, 88% of patients underwent surgical resection within a median 22 days (range, 11-74) and only 15% converted to thoracotomy.
“Our findings are comparable if not superior to historical findings in the neoadjuvant setting,” Lee said. “This study demonstrated that intraoperative complication rates were rare and mortality rates were superior to the expected historical outcomes.”
Moreover, median length of hospital stay was 7.5 days and 30-day mortality was 0.6%.
Results of exploratory analyses showed a 1-year DFS rate of 85% for stage IB to stage IIIB disease and 1-year OS rates of 92% for stage IB and stage IIB disease and 95% for stage IIIB disease.
“The LCMC3 study successfully met its primary endpoint of achieving major pathologic response and provides additional clinical evidence for the ongoing placebo-controlled phase 3 IMpower030 study of atezolizumab combined with platinum-based chemotherapy,” Lee said.
Precision medicine has transformed the clinical practice of lung cancer diagnosis and treatment. The increasing number of driver mutations, targeted therapies and immunotherapies have offered opportunities for patients with advanced lung cancer that have resulted in improved outcomes. These therapies have now moved into the earlier stages of lung cancer, including locally advanced disease with durvalumab (Imfinzi, AstraZeneca), as investigated in the PACIFIC trial.
Data from the ADUARA trial has led to biomarker testing for EGFR mutations in the surgically resectable population. Treatment with osimertinib (Tagrisso, AstraZeneca) improved DFS compared with placebo. The precision medicine paradigm has reinforced the clinical practice of biomarker testing in patients with lung cancer prior to initiating any therapy, a practice first done among patients with breast cancer. The ability to use less cytotoxic chemotherapy in lieu of biologic therapies has resulted in less toxicity and improved outcomes among patients with advanced lung cancer.
Neoadjuvant or induction approaches in patients with resectable lung cancer have been tested with cytotoxic chemotherapy. Adjuvant chemotherapy has been approved since the early 2000s but has not been used consistently due to efficacy or toxicity. Increasingly, targeted and immunotherapies are being studied in the neoadjuvant and adjuvant settings. Immunotherapies such as atezolizumab, as reported during the International Association for the Study of Lung Cancer World Conference on Lung Cancer, may offer a substitute for chemotherapy.
Challenges still exist, including how to best measure the impact of neoadjuvant therapy, such as by response rate, complete response and improved resectability, whether neoadjuvant and/or adjuvant therapies are needed, and the overall effectiveness based on disease stage. Further studies based on the precision medicine paradigm will help answer these questions and offer more opportunities for patients with curable lung cancer.
Perspective
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Edward S. Kim, MD, MBA, FACP, FASCO
Precision medicine has transformed the clinical practice of lung cancer diagnosis and treatment. The increasing number of driver mutations, targeted therapies and immunotherapies have offered opportunities for patients with advanced lung cancer that have resulted in improved outcomes. These therapies have now moved into the earlier stages of lung cancer, including locally advanced disease with durvalumab (Imfinzi, AstraZeneca), as investigated in the PACIFIC trial.
Data from the ADUARA trial has led to biomarker testing for EGFR mutations in the surgically resectable population. Treatment with osimertinib (Tagrisso, AstraZeneca) improved DFS compared with placebo. The precision medicine paradigm has reinforced the clinical practice of biomarker testing in patients with lung cancer prior to initiating any therapy, a practice first done among patients with breast cancer. The ability to use less cytotoxic chemotherapy in lieu of biologic therapies has resulted in less toxicity and improved outcomes among patients with advanced lung cancer.
Neoadjuvant or induction approaches in patients with resectable lung cancer have been tested with cytotoxic chemotherapy. Adjuvant chemotherapy has been approved since the early 2000s but has not been used consistently due to efficacy or toxicity. Increasingly, targeted and immunotherapies are being studied in the neoadjuvant and adjuvant settings. Immunotherapies such as atezolizumab, as reported during the International Association for the Study of Lung Cancer World Conference on Lung Cancer, may offer a substitute for chemotherapy.
Challenges still exist, including how to best measure the impact of neoadjuvant therapy, such as by response rate, complete response and improved resectability, whether neoadjuvant and/or adjuvant therapies are needed, and the overall effectiveness based on disease stage. Further studies based on the precision medicine paradigm will help answer these questions and offer more opportunities for patients with curable lung cancer.
References:
Antonia SJ, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1709937.
Wu Y-L, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa2027071.
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Lee JM, et al. Abstract PS01.05. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer (virtual meeting); Jan. 28-31, 2021.
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