Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer
Por:
Wu, YL, Tsuboi, M, He, J, John, T, Grohe, C, Majem, M, Goldman, JW, Laktionov, K, Kim, SW, Kato, T, Vu, HV, Lu, S, Lee, KY, Akewanlop, C, Yu, CJ, de Marinis, F, Bonanno, L, Domine, M, Shepherd, FA, Zeng, LM, Hodge, R, Atasoy, A, Rukazenkov, Y, Herbst, RS, ADAURA Investigators
Publicada:
29 oct 2020
Resumen:
BackgroundOsimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown.
MethodsIn this double-blind, phase 3 trial, we randomly assigned patients with completely resected EGFR mutation-positive NSCLC in a 1:1 ratio to receive either osimertinib (80 mg once daily) or placebo for 3 years. The primary end point was disease-free survival among patients with stage II to IIIA disease (according to investigator assessment). The secondary end points included disease-free survival in the overall population of patients with stage IB to IIIA disease, overall survival, and safety.
ResultsA total of 682 patients underwent randomization (339 to the osimertinib group and 343 to the placebo group). At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84 to 93) and 44% of those in the placebo group (95% CI, 37 to 51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11 to 0.26; P<0.001). In the overall population, 89% of the patients in the osimertinib group (95% CI, 85 to 92) and 52% of those in the placebo group (95% CI, 46 to 58) were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.20; 99.12% CI, 0.14 to 0.30; P<0.001). At 24 months, 98% of the patients in the osimertinib group (95% CI, 95 to 99) and 85% of those in the placebo group (95% CI, 80 to 89) were alive and did not have central nervous system disease (overall hazard ratio for disease recurrence or death, 0.18; 95% CI, 0.10 to 0.33). Overall survival data were immature; 29 patients died (9 in the osimertinib group and 20 in the placebo group). No new safety concerns were noted.
ConclusionsIn patients with stage IB to IIIA EGFR mutation-positive NSCLC, disease-free survival was significantly longer among those who received osimertinib than among those who received placebo. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.)
The incidence of recurrence after curative resection among patients with stage IB, II, or IIIA non-small-cell lung cancer is high and is only slightly lower with adjuvant chemotherapy. A randomized trial of adjuvant osimertinib involving patients with EGFR mutation-positive NSCLC showed a substantial decrease in recurrence. Central nervous system relapses were also significantly reduced.
Filiaciones:
Wu, YL:
Guangdong Prov Peoples Hosp, Guangdong Lung Canc Inst, Guangzhou 510080, Peoples R China
Guangdong Acad Med Sci, Guangzhou 510080, Peoples R China
Tsuboi, M:
Natl Canc Ctr Hosp East, Dept Thorac Surg & Oncol, Kashiwa, Chiba, Japan
He, J:
Chinese Acad Med Sci & Peking Union Med Coll, Thorac Surg Dept, Natl Canc Ctr, Natl Clin Res Ctr Canc,Canc Hosp, Beijing, Peoples R China
John, T:
Austin Hlth, Dept Med Oncol, Melbourne, Vic, Australia
Grohe, C:
Evangel Lungenklin, Dept Resp Dis, Berlin, Germany
Majem, M:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona, Spain
Goldman, JW:
Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA
Laktionov, K:
Russian Acad Med Sci, Ctr Innovat Technol & Oncol, NN Blokhin Russian Canc Ctr, Moscow, Russia
Kim, SW:
Univ Ulsan, Asan Med Ctr, Coll Med, Dept Oncol, Seoul, South Korea
Kato, T:
Kanagawa Canc Ctr, Dept Thorac Oncol, Yokohama, Kanagawa, Japan
Vu, HV:
Cho Ray Hosp, Dept Thorac Surg, Ho Chi Minh City, Vietnam
Lu, S:
Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Lung Canc Ctr, Shanghai, Peoples R China
Lee, KY:
Konkuk Univ, Med Ctr, Precis Med Lung Canc Ctr, Seoul, South Korea
Akewanlop, C:
Siriraj Hosp, Fac Med, Div Med Oncol, Bangkok, Thailand
Yu, CJ:
Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan
Natl Taiwan Univ, Coll Med, Taipei, Taiwan
de Marinis, F:
IRCCS, European Inst Oncol, Div Thorac Oncol, Milan, Italy
Bonanno, L:
IRCCS, Ist Oncol Veneto, Med Oncol, Padua, Italy
Domine, M:
Hosp Univ Fdn Jimenez Diaz, Dept Oncol, Madrid, Spain
Shepherd, FA:
Univ Hlth Network, Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada
Univ Toronto, Toronto, ON, Canada
Zeng, LM:
AstraZeneca, Late Oncol Stat, Gaithersburg, MD USA
Hodge, R:
AstraZeneca, Late Oncol Stat, Cambridge, England
Atasoy, A:
AstraZeneca, Oncol Res & Dev, Cambridge, England
Rukazenkov, Y:
AstraZeneca, Oncol Res & Dev, Cambridge, England
Herbst, RS:
Yale Sch Med, Sect Med Oncol, 333 Cedar St,POB 208028, New Haven, CT 06520 USA
Yale Canc Ctr, 333 Cedar St,POB 208028, New Haven, CT 06520 USA
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