1. Fuerst, Mark L.

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In an exploratory analysis of the Phase III IMpower010 trial, disease-free survival (DFS) was improved with adjuvant atezolizumab versus best supportive care in patients with non-small cell lung cancer (NSCLC) across most disease stages, those with nodal involvement, and across most surgery types and chemotherapy regimens.

NSCLC. NSCLC... - Click to enlarge in new windowNSCLC. NSCLC

"Patients who participated in the IMpower010 trial, including patients with nodal involvement, saw benefit across disease stages (Stage II-IIIA subpopulations)," said Nasser Altorki, MD, Professor of Cardiothoracic Surgery and the Director of the Division of Thoracic Surgery at NewYork-Presbyterian Hospital/Weill Cornell Medicine in New York City.


The Phase III IMpower010 trial evaluated atezolizumab versus best supportive care after surgical resection and adjuvant chemotherapy in patients with PD-L1-expressing (>=1%) Stage II or IIIA disease. The primary results of the trial, presented at the 2021 American Society of Clinical Oncology Annual Meeting, showed it met the primary endpoint with significant DFS improvement for patients with Stage II-IIIA NSCLC; the significance boundary for DFS was not crossed in the intention-to-treat (ITT) population (Stage IB-IIIA NSCLC).


The results of the exploratory analysis were presented at a Presidential Symposium during the IASLC 2021 World Conference on Lung Cancer.


Study Details

Altorki and co-investigators across 22 countries and regions enrolled 1,280 patients with completely resected Stage IB (tumors 4 or more cm)-IIIA NSCLC and an ECOG performance status of 0-1. Patients received up to 4 21-day cycles of cisplatin-based chemotherapy, and 1,005 patients were subsequently randomized to atezolizumab 1,200 mg every 3 weeks (16 cycles or until disease recurrence or unacceptable toxicity) or best supportive care.


In the new presentation, researchers examined the impact on DFS of therapies prior to adjuvant atezolizumab, including the extent of pulmonary resection, the type of mediastinal nodal assessment, and adjuvant chemotherapy regimens. These pre-randomization variables, as well as the time from surgery to adjuvant treatment, are topics of interest, said Altorki.


The primary endpoint of investigator-assessed DFS was tested hierarchically in the PD-L1 TC >=1 percent Stage II-IIIA population, all-randomized Stage II-IIIA population, and ITT population (Stage IB-IIIA). Surgery type, disease stage, mediastinal nodal assessment, and cisplatin-based chemotherapy regimens were well balanced between the atezolizumab and best supportive care arms, he said.


In the ITT population, the most common surgery was lobectomy (78.1%), followed by pneumonectomy (15.9%), and bilobectomy (5%). Mediastinal lymph node dissection or sampling was performed in 80.7 percent and 18 percent of patients, respectively.


The majority of patients across different chemotherapy treatments in both arms received the planned 4 cycles of chemotherapy. Chemotherapy regimens included cisplatin/pemetrexed (38%), cisplatin/vinorelbine (30%), cisplatin/gemcitabine (16%), and cisplatin/docetaxel (15%). In the ITT population, median time from surgery to first atezolizumab treatment or best supportive care was about 5 months in both arms.


In this exploratory analysis, the forest plots showed that DFS in the PD-L1 TC >=1 percent Stage II-IIIA and all-randomized Stage II-IIIA populations favored the atezolizumab versus best supportive care arm across most disease stages, surgery types, and chemotherapy regimens. "DFS was better for most disease stages, regardless of the type of surgery or the cisplatin doublet that was used," said Altorki.


Median DFS among patients with Stage II and IIIA disease was not reached for the atezolizumab arm and was 35.3 months for the best supportive care arm (HR 0.66). For all randomized patients, median DFS for atezolizumab was 42.3 months versus 35.3 months for best supportive care (HR 0.79). For the ITT population, the statistical significance boundary was not crossed. Median DFS was not reached with atezolizumab compared to 37.2 months for best supportive care (HR 0.81).


In the 882 randomly assigned patients with Stage II and IIIA NSCLC, DFS favored atezolizumab across most stages, types of surgery, and chemotherapy regimens. Results were similar in the ITT population, but Altorki reminded that the statistical boundary for this group has not yet been crossed. Atezolizumab was well-tolerated, and no new safety signals were identified, he noted.


In conclusion, Altorki said: "At the DFS interim analysis of IMpower010, atezolizumab showed statistically significant DFS benefit versus best supportive care in the PD-L1 TC >=1 percent Stage II-IIIA and all-randomized Stage II-IIIA populations. The main reasons patients were not randomized after enrollment were patient withdrawal and disease progression. In the ITT population, study arms were well-balanced with regard to disease stage, regional lymph node status, surgical intervention, and chemotherapy regimen. The majority of patients had lobectomy, lymph node dissection, and 4 cycles of adjuvant chemotherapy. The median time from surgery to start of randomized treatment or BSC was similar between study arms."


Mark L. Fuerst is a contributing writer.