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A phase Ib study of the combination of afatinib and ruxolitinib in EGFR mutant NSCLC with progression on EGFR-TKIs.
Lung Cancer 2019; 134:46-51LC

Abstract

OBJECTIVES

We evaluated the safety and efficacy of the combination therapy of afatinib, an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), and ruxolitinib, a JAK1/2 selective inhibitor, in patients with EGFR mutant NSCLC progressing on at least one kind of EGFR-TKI.

MATERIALS AND METHODS

In this phase Ib open-label study, we used a 3 + 3 dose-escalation design. Patients with histologically diagnosed EGFR-mutant stage IV NSCLC and documented disease progression on EGFR-TKI therapies were enrolled. Afatinib only was administered on day 1 through day 8 (run-in period), then ruxolitinib was administered concurrently with afatinib until disease progression. The primary endpoints were to determine the dose-limiting toxicity (DLT) and a recommended phase II dose of the combination regimen. We also included a dose confirmation cohort for the highest dose, and an expansion cohort for T790 M mutation.

RESULTS

As of October 2017, 30 patients participated in the study, of which 20 had T790 M mutations. Because no DLT was observed in nine patients at the highest dose level (50 mg afatinib once daily plus 25 mg ruxolitinib twice daily), nine patients with T790 M mutations were enrolled in a dose-expansion cohort. Frequent adverse events included diarrhea (G3 in 3 of 22 cases), anemia (G3 in 1 of 26 cases), paronychia (G1/2 in 14 cases), acneiform rash (G1 in 13 cases), and oral mucositis (G1/2 in 12 cases). Objective response rate was 23.3% (no complete response [CR] and 7 partial responses [PR]) and disease control rate was 93.3% (no CR, 7 PR and 21 stable diseases). The median progression-free survival was 4.9 months (95% CI, 2.4-7.5).

CONCLUSION

The combination of afatinib and ruxolitinib was tolerated by patients, with modest clinical activity observed in NSCLC with acquired resistance to EGFR-TKIs (NCT02145637).

Authors+Show Affiliations

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; Cancer Prevention Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: nobelg@yuhs.ac.Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: cbc1971@yuhs.ac.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31319994

Citation

Park, Ji Soo, et al. "A Phase Ib Study of the Combination of Afatinib and Ruxolitinib in EGFR Mutant NSCLC With Progression On EGFR-TKIs." Lung Cancer (Amsterdam, Netherlands), vol. 134, 2019, pp. 46-51.
Park JS, Hong MH, Chun YJ, et al. A phase Ib study of the combination of afatinib and ruxolitinib in EGFR mutant NSCLC with progression on EGFR-TKIs. Lung Cancer. 2019;134:46-51.
Park, J. S., Hong, M. H., Chun, Y. J., Kim, H. R., & Cho, B. C. (2019). A phase Ib study of the combination of afatinib and ruxolitinib in EGFR mutant NSCLC with progression on EGFR-TKIs. Lung Cancer (Amsterdam, Netherlands), 134, pp. 46-51. doi:10.1016/j.lungcan.2019.05.030.
Park JS, et al. A Phase Ib Study of the Combination of Afatinib and Ruxolitinib in EGFR Mutant NSCLC With Progression On EGFR-TKIs. Lung Cancer. 2019;134:46-51. PubMed PMID: 31319994.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A phase Ib study of the combination of afatinib and ruxolitinib in EGFR mutant NSCLC with progression on EGFR-TKIs. AU - Park,Ji Soo, AU - Hong,Min Hee, AU - Chun,You Jin, AU - Kim,Hye Ryun, AU - Cho,Byoung Chul, Y1 - 2019/05/28/ PY - 2019/02/11/received PY - 2019/05/03/revised PY - 2019/05/27/accepted PY - 2019/7/20/entrez KW - Afatinib KW - EGFR KW - Non-Small cell lung cancer (NSCLC) KW - Ruxolitinib KW - T790M SP - 46 EP - 51 JF - Lung cancer (Amsterdam, Netherlands) JO - Lung Cancer VL - 134 N2 - OBJECTIVES: We evaluated the safety and efficacy of the combination therapy of afatinib, an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), and ruxolitinib, a JAK1/2 selective inhibitor, in patients with EGFR mutant NSCLC progressing on at least one kind of EGFR-TKI. MATERIALS AND METHODS: In this phase Ib open-label study, we used a 3 + 3 dose-escalation design. Patients with histologically diagnosed EGFR-mutant stage IV NSCLC and documented disease progression on EGFR-TKI therapies were enrolled. Afatinib only was administered on day 1 through day 8 (run-in period), then ruxolitinib was administered concurrently with afatinib until disease progression. The primary endpoints were to determine the dose-limiting toxicity (DLT) and a recommended phase II dose of the combination regimen. We also included a dose confirmation cohort for the highest dose, and an expansion cohort for T790 M mutation. RESULTS: As of October 2017, 30 patients participated in the study, of which 20 had T790 M mutations. Because no DLT was observed in nine patients at the highest dose level (50 mg afatinib once daily plus 25 mg ruxolitinib twice daily), nine patients with T790 M mutations were enrolled in a dose-expansion cohort. Frequent adverse events included diarrhea (G3 in 3 of 22 cases), anemia (G3 in 1 of 26 cases), paronychia (G1/2 in 14 cases), acneiform rash (G1 in 13 cases), and oral mucositis (G1/2 in 12 cases). Objective response rate was 23.3% (no complete response [CR] and 7 partial responses [PR]) and disease control rate was 93.3% (no CR, 7 PR and 21 stable diseases). The median progression-free survival was 4.9 months (95% CI, 2.4-7.5). CONCLUSION: The combination of afatinib and ruxolitinib was tolerated by patients, with modest clinical activity observed in NSCLC with acquired resistance to EGFR-TKIs (NCT02145637). SN - 1872-8332 UR - https://www.unboundmedicine.com/medline/citation/31319994/A_phase_Ib_study_of_the_combination_of_afatinib_and_ruxolitinib_in_EGFR_mutant_NSCLC_with_progression_on_EGFR-TKIs L2 - https://linkinghub.elsevier.com/retrieve/pii/S0169-5002(19)30474-X DB - PRIME DP - Unbound Medicine ER -