Alectinib in Resected ALK-Positive Non–Small-Cell Lung Cancer

Author(s): Yi-Long Wu, M.D. https://orcid.org/0000-0002-3611-0258, Rafal Dziadziuszko, M.D., Ph.D., Jin Seok Ahn, M.D., Ph.D., Fabrice Barlesi, M.D., Ph.D., Makoto Nishio, M.D., Ph.D., Dae Ho Lee, M.D., Ph.D., Jong-Seok Lee, M.D., Ph.D., Wenzhao Zhong, M.D., Ph.D., Hidehito Horinouchi, M.D., Ph.D., Weimin Mao, M.D., Ph.D., Maximilian Hochmair, M.D., Filippo de Marinis, M.D., M. Rita Migliorino, M.D., Igor Bondarenko, M.D., Ph.D., Shun Lu, M.D., Qun Wang, M.D., Tania Ochi Lohmann, Ph.D., Tingting Xu, M.D., Andres Cardona, M.Sc., Thorsten Ruf, M.D., Johannes Noe, Ph.D., and Benjamin J. Solomon, M.B., B.S., Ph.D., for the ALINA Investigators*
Source: N Engl J Med 2024;390:1265-1276 DOI: 10.1056/NEJMoa2310532
Maem Hussein MD

Dr. Maen Hussein's Thoughts

This is another target for adjuvant therapy. The results are impressive. Notice that there was no chemotherapy in the study arm. Patients started on alectinib after surgery.
Chemotherapy is losing ground to more tolerable treatments, more to follow, most likely, in the future.

BACKGROUND

Platinum-based chemotherapy is the recommended adjuvant treatment for patients with resectable, ALK-positive non–small-cell lung cancer (NSCLC). Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected ALK-positive NSCLC are lacking.

METHODS

We conducted a global, phase 3, open-label, randomized trial in which patients with completely resected, ALK-positive NSCLC of stage IB (tumors ≥4 cm), II, or IIIA (as classified according to the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer and Union for International Cancer Control) were randomly assigned in a 1:1 ratio to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy in four 21-day cycles. The primary end point was disease-free survival, tested hierarchically among patients with stage II or IIIA disease and then in the intention-to-treat population. Other end points included central nervous system (CNS) disease–free survival, overall survival, and safety.

RESULTS

In total, 257 patients were randomly assigned to receive alectinib (130 patients) or chemotherapy (127 patients). The percentage of patients alive and disease-free at 2 years was 93.8% in the alectinib group and 63.0% in the chemotherapy group among patients with stage II or IIIA disease (hazard ratio for disease recurrence or death, 0.24; 95% confidence interval [CI], 0.13 to 0.45; P<0.001) and 93.6% and 63.7%, respectively, in the intention-to-treat population (hazard ratio, 0.24; 95% CI, 0.13 to 0.43; P<0.001). Alectinib was associated with a clinically meaningful benefit with respect to CNS disease–free survival as compared with chemotherapy (hazard ratio for CNS disease recurrence or death, 0.22; 95% CI, 0.08 to 0.58). Data for overall survival were immature. No unexpected safety findings were observed.

Among patients with resected ALK-positive NSCLC of stage IB, II, or IIIA, adjuvant alectinib significantly improved disease-free survival as compared with platinum-based chemotherapy. (Funded by F. Hoffmann–La Roche; ALINA ClinicalTrials.gov number, NCT03456076.)

Author Affiliations

From the Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou (Y.-L.W., W.Z.), the Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou (W.M.), and the Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (S.L.), the Department of Thoracic Surgery, Zhongshan Hospital, Fudan University (Q.W.), and the Department of Clinical Science, Roche (China) Holding (T.X.), Shanghai — all in China; the Department of Oncology and Radiotherapy and the Early Phase Clinical Trials Center, Medical University of Gdansk, Gdansk, Poland (R.D.); the Department of Hematology and Oncology, Samsung Medical Center (J.S.A.), and Asan Medical Center (D.H.L.), Seoul, and Seoul National University Bundang Hospital, Seongnam (J.-S.L.) — all in South Korea; the Department of Medical Oncology, International Center for Thoracic Cancers, Gustave Roussy, Villejuif, and Paris-Saclay University, Faculty of Medicine, Le Kremlin-Bicêtre — both in France (F.B.); the Cancer Institute Hospital, Japanese Foundation for Cancer Research (M.N.), and the Department of Thoracic Oncology, National Cancer Center Hospital (H.H.) — both in Tokyo; the Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna (M.H.); the Thoracic Oncology Division, European Institute of Oncology, IRCCS, Milan (F.M.); the Pneumo-Oncology Unit, San Camillo Forlanini Hospital, Rome (M.R.M.); the Oncology and Medical Radiology Department, Dnipropetrovsk State Medical Academy, Dnipro, Ukraine (I.B.); PD Oncology (T.O.L.), Data and Statistical Sciences (A.C.), PD Safety Risk Management (T.R.), and Translational Medicine (J.N.), F. Hoffmann–La Roche, Basel, Switzerland; and the Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.).

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Perioperative Nivolumab in Resectable Lung Cancer

Perioperative nivolumab (Nivo) showed a 20% 18-month EFPS improvement. This is another option to consider for your patients with stage IIA-IIIB NSCLC. Of note, the study arm received chemo + Nivo x 4 cycles preoperatively, then 12 months of Nivo therapy, and toxicities were as expected.

Read More »

Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer

FCS medical oncologist and hematologist Ernesto Bustinza-Linares, MD has co-authored an abstract published in the American Society of Clinical Oncology Journal, JCO Precision Oncology, that uncovers a new testing method to determine personalized care options for patients with metastatic non-small cell lung cancer (NSCLC). The abstract’s authors address the limitations of existing guidelines that recommend checkpoint immunotherapy, sometimes in combination with chemotherapy, for treating NSCLC, which often discounts patient variability and immune factors. The findings from the study show that by incorporating additional plasma proteome-based testing, combined with the standard protein inhibitor testing, clear differences in patient outcomes were observed after applying targeted treatments based on the testing results.

Read More »

Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor–Mutated Metastatic Non–Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722

This is the same issue as the Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04) article, this one was negative though. A question for the previous trial would be: do we need PDL-1 inhibitor, or just VEGF inhibitor, recall the pts with tumors with high PDL-1 expression did better though, so most likely we need both with chemotherapy.

Read More »

Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04)

Adding VEGF inhibitor to PD-1 blocker in addition to chemotherapy is better than a chemotherapy-alone regimen as a second-line therapy after TKI failure. This is true especially in patients with tumors with high PD-L1 expression, with not much besides chemotherapy as second-line therapy for those patients (or other clinical trials) that may be a better option that includes immunotherapy.

Read More »