Exploratory IMpower010 Analysis Shows Surgery Type Associated with Favorable DFS, OS Results

In stage II-IIIA NSCLC patients with high PD-L1 expression, the benefits of atezolizumab and platinum-based chemotherapy after surgical resection appeared to be most prominent in the lobectomy subgroup according to Dr. Alessandro Brunelli and colleagues.

By: Alessandro Brunelli, MD, Heather Wakelee, MD, Caicun Zhou, MD, PhD, Enriqueta Felip, PhD, Eric Vallières, MD, FRCSC, Benny Weksler, MD, Rüdiger Liersch, MD, Margarita Majem Tarruella, MD, PhD, Kimberly Costas, MD, Wei Zhang, PhD, Monika Kaul, MD, Marcus Ballinger, PhD, Virginia McNally, PhD, Elizabeth Bennett, Barbara J. Gitlitz, MD, and Nasser Altorki, MD

on: July 11, 2023In: Meeting News

Print Email

IMpower010 is the first phase III adjuvant cancer immunotherapy study to demonstrate a significant disease-free survival (DFS) benefit for early-stage NSCLC,1,2 leading to approval of atezolizumab in the US, the European Union, and other countries following adjuvant platinum-based chemotherapy for completely resected stage II-IIIA NSCLC patients with PD-L1 expression ≥1% in the US group and for >50% population in the EU.3,4

In previous reports from a prospective, phase III randomized clinical trial, atezolizumab, yielded a statistically significant DFS improvement compared to best supportive care in patients with PD-L1 expression ≥1% and stage II-IIIA NSCLC. The greatest DFS benefit was seen in patients with PD-L1 expression ≥50%.1 No new or unexpected safety signals were identified, and the safety profile of atezolizumab was consistent with prior experience.

In this subgroup analysis, authors investigated DFS and OS outcomes by surgery type in those patients with PD-L1 ≥50% and stage II-IIIA, excluding those with known EGFR/ALK+ disease.

As previously reported, this group of patients realized a 57% reduction in relapse or death after a median follow up of 32 months and a 58% overall survival benefit after a median follow up of 45 months compared to best supportive care in this setting.5,6

Baseline characteristics of the patients were balanced between the intervention and best supportive care groups. In addition, they were consistent with those in the intention-to-treat (ITT) population.

In patients with high PD-L1 expression, the most frequent procedure was lobectomy (74%-75%). Pneumonectomies accounted for 17%-18% of the total. These figures are consistent with those observed in the ITT population.

We found that in stage II-IIIA patients with PD-L1 ≥50% (excluding EGFR/ALK+ patients), the favorable DFS and OS HRs were mainly driven by the lobectomy subgroup. (See Figs. 1-2) The hazard ratio for DFS in the lobectomy subgroup was 0.34 and the hazard ratio for OS in the lobectomy group was 0.31.

Considering the small numbers of pneumonectomies and bilobectomies, the same benefits were not observed in those undergoing larger procedures.

Pneumonectomies/bilobectomies and lobectomies have previously been shown to result in the same adverse events profiles, with no increase of adverse events in the procedures larger than lobectomies. In addition, the occurrence of adverse events appeared balanced between the intervention and the best supportive care groups in all procedures.7

In conclusion, despite limited patient numbers across surgery types, efficacy outcomes in stage II-IIIA NSCLC patients with PD-L1 expression ≥50% without known EGFR/ALK alterations favored atezolizumab compared to best supportive care and appeared to be most prominent in the lobectomy subgroup. Adjuvant atezolizumab was well-tolerated, and no new safety signals were identified in patients who underwent pneumonectomy or bilobectomy.

These exploratory data support the use of adjuvant atezolizumab after complete resection and platinum-based chemotherapy in stage II-IIIA NSCLC patients with PD-L1 ≥50% without EGFR/ALK alterations.

References

1. Felip E, et al. Lancet 2021;398:1344-57;
2. Wakelee HA, et al. ASCO 2021. Abstract 8500;
3. TECENTRIQ (atezolizumab). Prescribing information. Genentech Inc; 2022;
4. TECENTRIQ (atezolizumab). Summary of product characteristics. Roche Registration GmbH; 2022
5. Wakelee H, et al. J Thorac Oncol 2022;17(suppl 2):PL03.09;
6. Felip E, et al. Ann Oncol 2022;33(suppl 2):S71.
7. Lee JM, et al. J Thorac Cardiovasc Surg. 2023 Jan 21:S0022-5223(23)00080-6. doi:10.1016/j.jtcvs.2023.01.012

Alessandro Brunelli, MD

Dr. Brunelli is consultant thoracic surgeon and honorary associate professor at St. James’s University Hospital, Leeds, UK

Heather Wakelee, MD

Dr. Wakelee is president of the IASLC and chief of the Division of Oncology at Stanford University as well as deputy director of the Stanford Cancer Institute, Stanford, California.

Caicun Zhou, MD, PhD

Dr. Zhou is president-elect of the IASLC and director of the Department of Oncology at Tongji University Shanghai Pulmonary Hospital in China

Enriqueta Felip, PhD

Dr. Felip is head of the Lung Cancer Unit in the Oncology Department at Vall d’Hebron University Hospital, Barcelona, Spain.

Eric Vallières, MD, FRCSC

Dr. Vallières is director of the Seattle, Washington-based Swedish Cancer Institute’s Lung Cancer Program. He has a special interest in lung cancer and mesothelioma and is one of the few US surgeons to perform extrapleural pneumonectomy.

Benny Weksler, MD

Dr. Weksler is professor of Cardiothoracic Surgery at Drexel University College of Medicine, Philadelphia

Rüdiger Liersch, MD

Dr. Liersch is head of the Oncological Center at Münster Alliance Against Cancer, University of Münster, Germany

Margarita Majem Tarruella, MD, PhD

Dr. Majem Tarruella is in the medical oncology department at Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

Kimberly Costas, MD

Dr. Costas specializes in robotic surgery and thoracic oncology at the Everett Clinic in Everett, Washington.

Wei Zhang, PhD

Dr. Zhang is professor of Cancer Biology at Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Monika Kaul, MD

Dr. Kaul is medical director and safety strategy leader of cancer immunotherapy for lung and head and neck cancers at Roche, San Francisco.

Marcus Ballinger, PhD

Dr. Ballinger is the global development lead for lung and head and neck cancer immunotherapy at Genentech, San Francisco.

Virginia McNally, PhD

Dr. McNally is associate group clinical science director for Roche Products Ltd, Welwyn Garden City, UK.

Elizabeth Bennett

Ms. Bennett works at Genentech Inc, South San Francisco.

Barbara J. Gitlitz, MD

Dr. Gitliz is senior medical director at Genentech Inc, South San Francisco.

Nasser Altorki, MD

Dr. Altorki is a professor of cardiothoracic surgery and director of the Division of Thoracic Surgery at New York-Presbyterian Hospital, Weill Cornell Medicine, New York.