IMpower150: Exploratory analysis of brain metastases development.

Authors

Federico Cappuzzo

Federico Cappuzzo

Azienda Unità Sanitaria Locale della Romagna, Ravenna, Italy

Federico Cappuzzo , Martin Reck , Mark A. Socinski , Tony S. K. Mok , Robert M. Jotte , Gene Grant Finley , Delvys Rodriguez-Abreu , Joachim Aerts , Howard West , Makoto Nishio , Liza C Villaruz , Shelly Coleman , Anthony Lee , Hans Kristian Vollan , Wei Yu , Roxana Ioana Sufan , Ilze Bara , Fabrice Barlesi

Organizations

Azienda Unità Sanitaria Locale della Romagna, Ravenna, Italy, LungenClinic, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany, AdventHealth Cancer Institute, Orlando, FL, The Chinese University of Hong Kong, Hong Kong, China, US Oncology Research and Rocky Mountain Cancer Centers, Denver, CO, Department of Medical Oncology, Allegheny General Hospital, Pittsburgh, PA, Hospital Universitario Insular de Gran Canaria, Las Palmas De Gran Canaria, Spain, Department of Pulmonology, Erasmus University Medical Center, Rotterdam, Netherlands, City of Hope Comprehensive Cancer Center, Duarte, CA, Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan, University of Pittsburgh Medical Center-Hillman Cancer Center, Pittsburgh, PA, Genentech, Inc., South San Francisco, CA, F. Hoffmann-La Roche, Ltd., Basel, Switzerland, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France

Research Funding

Pharmaceutical/Biotech Company
F. Hoffmann-La Roche, Ltd.

Background: In the global phase III IMpower150 study (NCT02366143), atezolizumab (atezo) + bevacizumab (bev) + chemo (carboplatin + paclitaxel [CP] (ABCP) showed significant improvements in PFS and OS vs BCP in patients with chemotherapy-naive metastatic NSCLC (Socinski et al. N Engl J Med 2018). Because bev has been shown to delay or prevent brain metastases progression in NSCLC (Fu et al. J Chemother 2016; Ilhan-Mutlu et al. Mol Can Ther 2016), exploratory analyses were conducted to assess the development of brain metastases in patients treated with ABCP, BCP and atezo + CP (ACP) in IMpower150. Methods: A total of 1202 patients (intention-to-treat [ITT] population) were randomized 1:1:1 to receive ABCP, ACP or BCP. Doses were given every 3 weeks: atezo 1200 mg, bev 15 mg/kg, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m2. Co-primary endpoints were investigator-assessed PFS and OS in ITT–wild-type (no EGFR or ALK alterations) patients. Exploratory analyses included the rate and time to development (TTD) of new brain metastases in the ITT population, regardless of the presence of baseline brain metastases, as well as safety. Brain scans were performed as clinically indicated, and analyses were based on investigator assessments. Results: With a minimum follow-up of 32.4 months in the ITT population (data cutoff: September 13, 2019), 100 patients had developed brain metastases, with the highest rate of new brain lesions seen in the ACP (11.9%) vs the ABCP (7.0%) and BCP (6.0%) arms (table). Median TTD was not reached in any arm; a trend toward delayed TTD was seen in the ABCP vs BCP arm (HR, 0.68 [95% CI: 0.39, 1.19]). Among patients with and without brain metastases, 17 (35.4%) and 155 (44.0%) in the ACP arm, 18 (64.3%) and 207 (56.7%) in the ABCP arm and 10 (41.7%) and 183 (49.5%) in the BCP arm had Grade 3-4 treatment-related adverse events, respectively. Conclusions: The ACP arm had the highest rate of new brain lesions, whereas the ABCP and BCP arms had similar, lower rates. Taken together with the trend toward delayed development of new brain lesions with ABCP, the data suggest that adding atezo to BCP may not reduce the rate of new brain lesion development but may delay the time to new lesion development. No new safety signals were observed in this exploratory analysis. Clinical trial information: NCT02366143.

ACP
n = 402
ABCP
n = 400
BCP
n = 400
New Brain Lesions
Yes, n (%)48 (11.9)28 (7.0)24 (6.0)
No, n (%)354 (88.1)372 (93.0)376 (94.0)
Time to New Brain Lesions
Median (range), monthsNE (0-46.9)NE (0-45.9)NE (0-42.3)
HR (95% CI)1.55 (0.95, 2.55)0.68 (0.39, 1.19)NA
P value* (log-rank)0.080.17NA

NE, not estimable.

*P value is for descriptive purpose only.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Lung Cancer—Non-Small Cell Metastatic

Track

Lung Cancer

Sub Track

Metastatic Non–Small Cell Lung Cancer

Clinical Trial Registration Number

NCT02366143

Citation

J Clin Oncol 38: 2020 (suppl; abstr 9587)

DOI

10.1200/JCO.2020.38.15_suppl.9587

Abstract #

9587

Poster Bd #

353

Abstract Disclosures