Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial
Open accessAbstract
Background Alectinib--a highly selective, CNS-active, ALK inhibitor-showed promising clinical activity in crizotinib-naive and crizotinib-resistant patients with ALK-rearranged (ALK-positive) non-small-cell lung cancer (NSCLC). We aimed to assess the safety and efficacy of alectinib in patients with ALK-positive NSCLC who progressed on previous crizotinib.Methods We did a phase 2 study at 27 centres in the USA and Canada. We enrolled patients aged 18 years or older with stage IIIB-IV, ALK-positive NSCLC who had progressed after crizotinib. Patients were treated with oral alectinib 600 mg twice daily until progression, death, or withdrawal. The primary endpoint was the proportion of patients achieving an objective response by an independent review committee using Response Evaluation Criteria in Solid Tumors, version 1.1. Response endpoints were assessed in the response-evaluable population (ie, patients with measurable disease at baseline who received at least one dose of study drug), and efficacy and safety analyses were done in the intention-to-treat population (all enrolled patients). This study is registered with ClinicalTrials.gov, number NCT01871805. The study is ongoing and patients are still receiving treatment.Findings Between Sept 4, 2013, and Aug 4, 2014, 87 patients were enrolled into the study (intention-to-treat population). At the time of the primary analysis (median follow-up 4·8 months [IQR 3·3-7·1]), 33 of 69 patients with measurable disease at baseline had a confirmed partial response; thus, the proportion of patients achieving an objective response by the independent review committee was 48% (95% CI 36-60). Adverse events were predominantly grade 1 or 2, most commonly constipation (31 [36%]), fatigue (29 [33%]), myalgia 21 [24%]), and peripheral oedema 20 [23%]). The most common grade 3 and 4 adverse events were changes in laboratory values, including increased blood creatine phosphokinase (seven [8%]), increased alanine aminotransferase (five [6%]), and increased aspartate aminotransferase (four [5%]). Two patients died: one had a haemorrhage (judged related to study treatment), and one had disease progression and a history of stroke (judged unrelated to treatment).Interpretation Alectinib showed clinical activity and was well tolerated in patients with ALK-positive NSCLC who had progressed on crizotinib. Therefore, alectinib could be a suitable treatment for patients with ALK-positive disease who have progressed on crizotinib.Funding F Hoffmann-La Roche.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In another small cohort of patients with measurable brain disease in a phase 2 trial, 75% achieved an intracranial objective response.
“In another small cohort of patients with measurable brain disease being enrolled in another phase 2 trial, 75% of patients achieved an intracranial objective response [141].”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [141]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660 · see citing works
Toxicity and response criteria of the Eastern Cooperative Oncology Group
Oken, M. M., Creech, R. H., Tormey, D. C., Horton, J., Davis, T. E., Mcfadden, E. T., & Carbone, P. P. (1982) · American Journal of Clinical Oncology · doi:10.1097/00000421-198212000-00014 · Cited by 11,607 · see citing works
Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Soda, M., Choi, Y. L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., Fujiwara, S.-I., Watanabe, H., Kurashina, K., Hatanaka, H., et al. (2007) · Nature · doi:10.1038/nature05945 · Cited by 5,439 · see citing works
Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer
Kwak, E. L., Bang, Y., Camidge, D. R., Shaw, A. T., Solomon, B., Maki, R. G., Ou, S. I., Dezube, B. J., Janne, P. A., Costa, D. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1006448 · Cited by 4,442 · see citing works
Self-citationWen, P. Y., Macdonald, D. R., Reardon, D. A., Cloughesy, T. F., Sorensen, A. G., Galanis, E., DeGroot, J. F., Wick, W., Gilbert, M. R., Lassman, A. B., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.3541 · Cited by 3,814 · see citing works
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-citationCeritinib in <i>ALK</i> -Rearranged Non–Small-Cell Lung Cancer
Shaw, A. T., Kim, D.-W., Mehra, R., Tan, D. S. W., Felip, E., Chow, L. Q. M., Camidge, D. R., Vansteenkiste, J., Sharma, S., De Pas, T., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1311107 · Cited by 1,495 · see citing works
Self-citationMechanisms of Acquired Crizotinib Resistance in ALK-Rearranged Lung Cancers
Katayama, R., Shaw, A. T., Khan, T. M., Mino-Kenudson, M. A., Solomon, B., Halmos, B., Jessop, N. A., Wain, J. C., Yeo, A. T., Benes, C. H., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003316 · Cited by 1,316 · see citing works
Self-citationEML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors
Choi, Y. L., Soda, M., Yamashita, Y., Ueno, T., Takashima, J., Nakajima, T., Yatabe, Y., Takeuchi, K., Hamada, T., Haruta, H., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1007478 · Cited by 1,186 · see citing works
Doebele, R. C., Pilling, A. B., Aisner, D. L., Kutateladze, T. G., Le, A. T., Weickhardt, A. J., Kondo, K. L., Linderman, D. J., Heasley, L. E., Franklin, W. A., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2906 · Cited by 1,064 · see citing works
Self-citationPatient-derived models of acquired resistance can identify effective drug combinations for cancer
Crystal, A. S., Shaw, A. T., Sequist, L. V., Friboulet, L., Niederst, M. J., Lockerman, E. L., Frias, R. L., Gainor, J. F., Amzallag, A., Greninger, P., et al. (2014) · Science · doi:10.1126/science.1254721 · Cited by 708 · see citing works
Self-citationGadgeel, S. M., Gandhi, L., Riely, G. J., Chiappori, A., West, H., Azada, M. C., Morcos, P. N., Lee, R.-M., Garcia, L., Yu, L. J., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70362-6 · Cited by 702 · see citing works
Self-citationCH5424802, a Selective ALK Inhibitor Capable of Blocking the Resistant Gatekeeper Mutant
Sakamoto, H., Tsukaguchi, T., Hiroshima, S., Kodama, T., Kobayashi, T., Fukami, T. A., Oikawa, N., Tsukuda, T., Ishii, N., & Aoki, Y. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.04.004 · Cited by 645 · see citing works
Costa, D. B., Shaw, A. T., Ou, S. I., Solomon, B., Riely, G. J., Ahn, M., Zhou, C., Shreeve, S. M., Selaru, P., Polli, A., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.0539 · Cited by 603 · see citing works
Self-citationCSF Concentration of the Anaplastic Lymphoma Kinase Inhibitor Crizotinib
Costa, D. B., Kobayashi, S. S., Pandya, S. S., Yeo, W.-L., Shen, Z., Tan, W., & Wilner, K. D. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.34.1313 · Cited by 601 · see citing works
Ou, S. I., Ahn, J. S., Petris, L. D., Govindan, R., Yang, J. C., Hughes, B. G. M., Léna, H., Moro‐Sibilot, D., Bearz, A., Viteri, S., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.63.9443 · Cited by 584 · see citing works
Self-citationSeto, T., Kiura, K., Nishio, M., Nakagawa, K., Maemondo, M., Inoue, A., Hida, T., Yamamoto, N., Yoshioka, H., Harada, M., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70142-6 · Cited by 575 · see citing works
Zou, H. Y., Friboulet, L., Kodack, D. P., Engstrom, L. D., Li, Q., West, M., Tang, R. W., Wang, H., Tsaparikos, K. E., Wang, J., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.05.010 · Cited by 473 · see citing works
Self-citationRationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer
Lovly, C. M., McDonald, N. T., Chen, H., Ortiz-Cuaran, S., Heukamp, L. C., Yan, Y., Florin, A., Ozretić, L., Lim, D., Wang, L., et al. (2014) · Nature Medicine · doi:10.1038/nm.3667 · Cited by 268 · see citing works
Katayama, R., Lovly, C. M., & Shaw, A. T. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2791 · Cited by 259 · see citing works
Self-citationAntitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases
Kodama, T., Hasegawa, M., Takanashi, K., Sakurai, Y., Kondoh, O., & Sakamoto, H. (2014) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-014-2578-6 · Cited by 242 · see citing works
Gainor, J. F., Sherman, C. A., Willoughby, K., Logan, J., Kennedy, E., Brastianos, P. K., Chi, A. S., & Shaw, A. T. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000455 · Cited by 168 · see citing works
Self-citationCamidge, D. R., Bazhenova, L. A., Salgia, R., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.8062 · Cited by 61 · see citing works
Self-citationShaw, A. T., Mehra, R., Tan, D. S. W., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu349.72 · Cited by 32 · see citing works
Self-citationTamura, T., Seto, T., Nakagawa, K., et al. (2014) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2014.08.031 · Cited by 14 · see citing works
Solomon, B., Felip, E., Blackhall, F. H., Mok, T. S. K., Kim, D.-H., Wu, Y.-L. L. C., Nakagawa, K., Mekhail, T. M., Paolini, J., Usari, T., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu349.4 · Cited by 13 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The biology and management of non-small cell lung cancer
Herbst, R. S., Morgensztern, D., & Boshoff, C. (2018) · Nature · doi:10.1038/nature25183 · Cited by 4,891 · see citing works
A view on drug resistance in cancer
Vasan, N., Baselga, J., & Hyman, D. M. (2019) · Nature · doi:10.1038/s41586-019-1730-1 · Cited by 2,770 · see citing works
Novello, S., Barlesi, F., Califano, R., Cufer, T., Ekman, S., Levra, M. G., Kerr, K., Popat, S., Reck, M., Senan, S., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw326 · Cited by 2,631 · see citing works
Alectinib versus Crizotinib in Untreated <i>ALK</i> -Positive Non–Small-Cell Lung Cancer
Peters, S., Camidge, D. R., Shaw, A. T., Gadgeel, S., Ahn, J. S., Kim, D.-W., Ou, S.-H. I., Pérol, M., Dziadziuszko, R., Rosell, R., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1704795 · Cited by 2,527 · see citing works
Self-citationSolomon, B. J., Besse, B., Bauer, T. M., Felip, E., Soo, R. A., Camidge, D. R., Chiari, R., Bearz, A., Lin, C.-C., Gadgeel, S. M., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30649-1 · Cited by 791 · see citing works
Self-citationYoda, S., Lin, J. J., Lawrence, M. S., Burke, B. J., Friboulet, L., Langenbucher, A., Dardaei, L., Prutisto-Chang, K., Dagogo-Jack, I., Timofeevski, S., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1256 · Cited by 322 · see citing works
Self-citationScientific Advances in Lung Cancer 2015
Tsao, A. S., Scagliotti, G. V., Bunn, P. A., Carbone, D. P., Warren, G. W., Bai, C., de Koning, H. J., Yousaf-Khan, A. U., McWilliams, A., Tsao, M. S., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.03.012 · Cited by 284 · see citing works
Toward a More Precise Future for Oncology
Murciano-Goroff, Y. R., Taylor, B. S., Hyman, D. M., & Schram, A. M. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.03.014 · Cited by 48 · see citing works
- Authors
- Shaw, A. T., Gandhi, L., Gadgeel, S., Riely, G. J., Cetnar, J., West, H., Camidge, D. R., Socinski, M. A., Chiappori, A., Mekhail, T., Chao, B. H., Borghaei, H., Gold, K. A., Zeaiter, A., Bordogna, W., Balas, B., Puig, O., Henschel, V., & Ou, S.-H. I.
- Affiliations
- Massachusetts General Hospital (US)
- Dana-Farber Cancer Institute (US)
- Wayne State University (US)
- Memorial Sloan Kettering Cancer Center (US)
- Oregon Health & Science University (US)
- Swedish Medical Center (US)
- University of Colorado Boulder (US)
- University of Pittsburgh Medical Center (US)
- Moffitt Cancer Center (US)
- Florida Hospital Cancer Institute (US)
- The Ohio State University (US)
- Fox Chase Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- F. Hoffmann-La Roche AG (CH)
- University of California, Irvine (US)
- Corresponding author
- Shaw, Alice T
- ORCID
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 17
- Issue
- 2
- Pages
- 234-242
- ISSN
- 1470-2045 (ISSN-L)
- PMC
- PMC4752892
- OpenAlex
- W2208535430
- Cited by
- 638
- References
- 27
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 22 · 2023: 36 · 2022: 31 · 2021: 55 · 2020: 64 · 2019: 72 · 2018: 101 · 2017: 139 · 2016: 87 · 2015: 1 · 2014: 2
- FWCI
- 86.48
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-03-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- US National Institutes of Health grant (5R01CA164273)
- 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
- alectinib, ALK-positive non-small cell lung cancer, crizotinib resistance, ALK inhibitors, second-line therapy, objective response rate, adverse events, central nervous system metastasis, treatment efficacy and safety, ALK rearrangement, tyrosine kinase inhibitors, progression-free survival, overall survival, constipation, creatine kinase elevation, peripheral edema
- MeSH terms
- Crizotinib, Anaplastic Lymphoma Kinase, Adult, Aged, Alanine Transaminase, Antineoplastic Agents, Aspartate Aminotransferases, Carbazoles, Carcinoma, Non-Small-Cell Lung, Constipation, Creatine Kinase, Edema, Fatigue, Female, Humans, Lung Neoplasms, Male, Middle Aged, Piperidines, Pyrazoles, Pyridines, Drug Resistance, Neoplasm, Retreatment, Receptor Protein-Tyrosine Kinases, Myalgia, Response Evaluation Criteria in Solid Tumors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
