Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001
Open accessAbstract
BACKGROUND: In the ongoing phase I PROFILE 1001 study, crizotinib showed antitumor activity in patients with ROS1-rearranged advanced non-small-cell lung cancer (NSCLC). Here, we present updated antitumor activity, overall survival (OS) and safety data (additional 46.2 months follow-up) for patients with ROS1-rearranged advanced NSCLC from PROFILE 1001. PATIENTS AND METHODS: ROS1 status was determined by FISH or reverse transcriptase-polymerase chain reaction. All patients received crizotinib at a starting dose of 250 mg twice daily. RESULTS: Fifty-three patients received crizotinib, with a median duration of treatment of 22.4 months. At data cut-off, treatment was ongoing in 12 patients (23%). The objective response rate (ORR) was 72% [95% confidence interval (CI), 58% to 83%], including six confirmed complete responses and 32 confirmed partial responses; 10 patients had stable disease. Responses were durable (median duration of response 24.7 months; 95% CI, 15.2-45.3). ORRs were consistent across different patient subgroups. Median progression-free survival was 19.3 months (95% CI, 15.2-39.1). A total of 26 deaths (49%) occurred (median follow-up period of 62.6 months), and of the remaining 27 patients (51%), 14 (26%) were in follow-up at data cut-off. Median OS was 51.4 months (95% CI, 29.3 to not reached) and survival probabilities at 12, 24, 36, and 48 months were 79%, 67%, 53%, and 51%, respectively. No correlation was observed between OS and specific ROS1 fusion partner. Treatment-related adverse events (TRAEs) were mainly grade 1 or 2, per CTCAE v3.0. There were no grade ≥4 TRAEs and no TRAEs associated with permanent discontinuation. No new safety signals were reported with long-term crizotinib treatment. CONCLUSIONS: These findings serve as a new benchmark for OS in ROS1-rearranged advanced NSCLC, and continue to show the clinically meaningful benefit and safety of crizotinib in this molecular subgroup. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT00585195.
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First-line crizotinib versus chemotherapy showed higher ORR and longer median PFS, but CNS metastases developed in nearly 50% of patients with ROS1+ NSCLC.
“While a higher objective response rate (ORR) and longer median progression-free survival (PFS) were observed with first-line crizotinib versus chemotherapy (CT), CNS metastases developed in nearly 50% of patients with ROS1+ NSCLC.10-13”
From Taletrectinib in <i>ROS1</i> + Non–Small Cell Lung Cancer: TRUST (2025) · cites this paper as [11]
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Crizotinib versus Chemotherapy in Advanced <i>ALK</i> -Positive Lung Cancer
Shaw, A. T., Kim, D.-W., Nakagawa, K., Seto, T., Crinó, L., Ahn, M.-J., De Pas, T., Besse, B., Solomon, B. J., Blackhall, F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1214886 · Cited by 3,381 · see citing works
Self-citationFirst-Line Crizotinib versus Chemotherapy in <i>ALK</i> -Positive Lung Cancer
Solomon, B. J., Mok, T., Kim, D.-W., Wu, Y.-L., Nakagawa, K., Mekhail, T., Felip, E., Cappuzzo, F., Paolini, J., Usari, T., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408440 · Cited by 3,190 · see citing works
Self-citationGlobal Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer
Rikova, K., Guo, A., Zeng, Q., Possemato, A., Yu, J., Haack, H., Nardone, J., Lee, K., Reeves, C., Li, Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.11.025 · Cited by 2,317 · see citing works
Crizotinib in <i>ROS1</i>-Rearranged Non–Small-Cell Lung Cancer
Shaw, A. T., Ou, S.-H. I., Bang, Y.-J., Camidge, D. R., Solomon, B. J., Salgia, R., Riely, G. J., Varella-Garcia, M., Shapiro, G. I., Costa, D. B., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1406766 · Cited by 1,964 · see citing works
Self-citation<i>ROS1</i> Rearrangements Define a Unique Molecular Class of Lung Cancers
Bergethon, K., Shaw, A. T., Ignatius Ou, S.-H., Katayama, R., Lovly, C. M., McDonald, N. T., Massion, P. P., Siwak-Tapp, C., Gonzalez, A., Fang, R., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.35.6345 · Cited by 1,555 · see citing works
Self-citationIdentifying and Targeting ROS1 Gene Fusions in Non–Small Cell Lung Cancer
Davies, K. D., Le, A. T., Theodoro, M. F., Skokan, M. C., Aisner, D. L., Berge, E. M., Terracciano, L., Cappuzzo, F., Incarbone, M., Roncalli, M. G., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0550 · Cited by 466 · see citing works
Self-citationSolomon, B., Kim, D., Wu, Y.-L. L. C., Nakagawa, K., Mekhail, T. M., Felip, E., Cappuzzo, F., Paolini, J., Usari, T., Tang, Y., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.77.4794 · Cited by 408 · see citing works
Self-citationWu, Y.-L. L. C., Yang, J. C., Kim, D., Lü, S., Zhou, J., Seto, T., Yang, J., Yamamoto, N., Ahn, M., Takahashi, T., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.75.5587 · Cited by 327 · see citing works
Self-citationLim, S. M., Kim, H. R., Lee, J.-S., Lee, K. H., Lee, Y., Min, Y. J., Cho, E. K., Lee, S. S., Kim, B.-S., Choi, M. Y., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.3701 · Cited by 305 · see citing works
Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial
Moro‐Sibilot, D., Cozic, N., Pérol, M., Mazières, J., Otto, J., Souquet, P. J., Bahleda, R., Wislez, M., Zalcman, G., de Guibert, S., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz407 · Cited by 197 · see citing works
Ou, S. I. (2011) · Drug Design Development and Therapy · doi:10.2147/dddt.s19045 · Cited by 186 · see citing works
Self-citationDziadziuszko, R., Krebs, M., de Braud, F., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.20.03025 · Cited by 166 · see citing works
Doebele, R. C., Ahn, M., Siena, S., et al. (2018) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.08.239 · Cited by 46 · see citing works
Papadopoulos, K. P., Gandhi, L., Janne, P. A., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.15_suppl.2514 · Cited by 18 · see citing works
Ou, S.-H. I., Shaw, A. T., Riely, G. J., et al. (2018) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.08.241 · Cited by 18 · see citing works
Self-citationOA12.03 Activity of Crizotinib in MET or ROS1 Positive (+) NSCLC: Results of the AcSé Trial.
Moro‐Sibilot, D., Cozic, N., Pérol, M., et al. (2018) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.08.301 · Cited by 16 · see citing works
Lin, J. J., Kim, D. S., Drilon, A. E. D. C., Doebele, R. C., Lee, J., Zhu, V. W., Ahn, M., Lim, J. S. J., Stopatschinskaja, S., Cui, J. J., et al. (2018) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.08.240 · Cited by 9 · see citing works
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Ettinger, D. S., Wood, D. E., Aisner, D. L., Akerley, W., Bauman, J. R., Bharat, A., Bruno, D. S., Chang, J. Y., Chirieac, L. R., D’Amico, T. A., et al. (2021) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2021.0013 · Cited by 948 · see citing works
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Min, H.-Y., & Lee, H.-Y. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00864-3 · Cited by 569 · see citing works
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Drilon, A., Camidge, D. R., Lin, J. J., Kim, S.-W., Solomon, B. J., Dziadziuszko, R., Besse, B., Goto, K., de Langen, A. J., Wolf, J., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2302299 · Cited by 240 · see citing works
Self-citationLin, J. J., Choudhury, N. J., Yoda, S., Zhu, V. W., Johnson, T. W., Sakhtemani, R., Dagogo-Jack, I., Digumarthy, S. R., Lee, C., Do, A., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0032 · Cited by 145 · see citing works
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Drilon, A., Chiu, C.-H., Fan, Y., Cho, B. C., Lu, S., Ahn, M.-J., Krebs, M. G., Liu, S. V., John, T., Otterson, G. A., et al. (2022) · JTO Clinical and Research Reports · doi:10.1016/j.jtocrr.2022.100332 · Cited by 113 · see citing works
Taletrectinib in <i>ROS1</i> + Non–Small Cell Lung Cancer: TRUST
Pérol, M., Li, W., Pennell, N. A., Liu, G., Ohe, Y., De Braud, F., Nagasaka, M., Felip, E., Xiong, A., Zhang, Y., et al. (2025) · Journal of Clinical Oncology · doi:10.1200/jco-25-00275 · Cited by 63 · see citing works
Drilon, A., Horan, J. C., Tangpeerachaikul, A., Besse, B., Ou, S.-H. I., Gadgeel, S. M., Camidge, D. R., van der Wekken, A. J., Nguyen-Phuong, L., Acker, A., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0968 · Cited by 52 · see citing works
Self-citationAdvances and future directions in <i>ROS1</i> fusion-positive lung cancer
Boulanger, M. C., Schneider, J. L., & Lin, J. J. (2024) · The Oncologist · doi:10.1093/oncolo/oyae205 · Cited by 38 · see citing works
- Authors
- Shaw, A. T., Riely, G. J., Bang, Y.-J., Kim, D.-W., Camidge, D. R., Solomon, B. J., Varella-Garcia, M., Iafrate, A. J., Shapiro, G. I., Usari, T., Wang, S. C., Wilner, K. D., Clark, J. W., & Ou, S.-H. I.
- Affiliations
- Massachusetts General Hospital (US)
- Memorial Sloan Kettering Cancer Center (US)
- Seoul National University (KR)
- University of Colorado Cancer Center (US)
- Peter MacCallum Cancer Centre (AU)
- Dana-Farber Cancer Institute (US)
- University of California, Irvine (US)
- Corresponding author
- Shaw, A.T.
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 30
- Issue
- 7
- Pages
- 1121-1126
- ISSN
- 0923-7534 (ISSN-L)
- PMC
- PMC6637370
- OpenAlex
- W2938245541
- Cited by
- 576
- References
- 17
- Citations by year
- 2026: 42 · 2025: 76 · 2024: 86 · 2023: 90 · 2022: 100 · 2021: 85 · 2020: 69 · 2019: 25 · 2017: 1
- FWCI
- 51.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- PROFILE 1001 study (NCT00585195)
- Pfizer Inc. (10.13039/100004319)
- Springer Healthcare
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- crizotinib, ROS1 rearrangement, advanced non-small cell lung cancer, overall survival, anticancer activity, objective response rate, progression-free survival, treatment-related adverse events, tyrosine kinase inhibitors, long-term follow-up, drug safety and tolerability, targeted therapy
- MeSH terms
- Crizotinib, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Female, Follow-Up Studies, Humans, Lung Neoplasms, Male, Middle Aged, Prognosis, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Retrospective Studies, Gene Rearrangement, Cohort Studies, Survival Rate
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