1471P - Final result of randomized phase 2 trial comparing amrubicin (A) with re-challenge of platinum doublet (P) in patients (pts) with sensitive-relapse...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Small-Cell Lung Cancer
Presenter Makoto Maemondo
Citation Annals of Oncology (2014) 25 (suppl_4): iv511-iv516. 10.1093/annonc/mdu355
Authors M. Maemondo1, A. Inoue2, S. Sugawara3, Y. Mori4, S. Oizumi5, M. Harada6, K. Taima7, N. Morikawa8, T. Ishida9, I. Kinoshita10, H. Watanabe11, T. Suzuki4, T. Nakagawa12, R. Saito2, T. Nukiwa13
  • 1Respiratory Medicine, Miyagi Cancer Center, 981-1293 - Natori/JP
  • 2Department Of Respiratory Medicine, Tohoku University, JP-980-8575 - Sendai/JP
  • 3Department Of Respiratory Medicine, Sendai Kousei Hospital, Sendai/JP
  • 4Division Of Respiratory Medicine, Iwate Prefectural Central Hospital, Morioka/JP
  • 5First Department Of Medicine, Hokkaido University School of Medicine, 060-8638 - Sapporo/JP
  • 6Department Of Pulmonary Disease, National Hospital Organization Hokkaido Cancer Center, 0030804 - Sapporo/JP
  • 7Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki/JP
  • 8Pulmonary Medicine,allergy And Rheumatology, Iwate medical university school of medicine, Iwate/JP
  • 9Clinical Oncology Center, Fukushima Medical University, 960-1295 - Fukushima/JP
  • 10Department Of Medical Oncology, Hokkaido University Graduate School of Medicine, 0608638 - Sapporo/JP
  • 11Respiratory Medicine, Saka genaral hospital, Shiogama/JP
  • 12Thoracic Surgery, omagari-kosei medical center, omagari/JP
  • 13Medical Commisioner, South Miyagi Medical Center, 9891253 - Miyagi/JP

Abstract

Aim

When this trial was planned, A was believed to be a promising new anthracycline agent for sensitive-relapsed SCLC. While re-challenge of P that had been used for the first-line treatment was also believed to be effetive for sensitive-relapsed SCLC, although prospective evaluation of it had not been reported. Thus this randomized phase 2 study was conducted to select A or P for future phase 3 trial.

Methods

Sensitive-ralapsed SCLC pts were randomized to receive A (40mg/m2, day1-3, every 3 weeks) or P (every 3-4 weeks). The modification of P such as the 20%-dose reduction of combined third-generation or change of platinum agent from cisplatin to carboplatin according to patient's condition was permitted. The primary endpoint was overall response rate (ORR), and secondary endpoint were progression-free survival (PFS), overall survival (OS), and toxicity profile. According to the Simon's two-stage phase 2 design, 28 pts were required in each arm (p0=0.3, p1=0.5, alpha=0.01, beta=0.02), and the treatment that achieved not less 12 out of 28 pts with partial response would be judged as effective.

Results

From February 2008 to June 2013, 60 pts were enrolled from 14 institutions. Two patients in the A arm and one patient in the P arm did not receive any protocol treatment due to rapid disease progression. Evaluated patients' characteristics were as follows: Male/Female, 53/4; median age, 66 (range 44-80); performance status 0/1/2, 32/21/4. The median number of treatment cycles was 4 (range 2-8) in A arm and 3 (range 1-7) in P arm. ORRs and disease control rates were 67% (95%CI, 50-84) and 86% for A, and 43% (95%CI, 25-61) and 80% for P, respectively. Mdian PFS and OS were 5.4 months and 14.4 months in A arm, and 5.1 months and 14.3 months in P arm. Grade 3 toxicity was observed in 33% of patients in A arm including 19% of febrile neutorpenia, while 17% in P arm without any febrile neutropenia. There was no grade 4 toxicity or treatment-related death in this trial.

Conclusions

Both treatments met the primary endpoint. Since A produced higher ORR and longer median PFS than P with acceptable toxicity, we select A for subsequent phase 3 trial.

Disclosure

All authors have declared no conflicts of interest.