The rEECur trial (ISRCTN36453794) is a multi-arm, multistage phase 2/3 “drop-a-loser” randomized trial designed to find the standard of care. The trial compares 4 chemotherapy regimens to each other and drops the least effective one after 50 patients per arm are enrolled and evaluated. The 3 remaining regimens continue until at least 75 patients on each arm are enrolled and evaluated, and then another arm would be dropped. The 2 remaining regimens continue to phase 3 evaluation. Four regimens are being tested at 8 centers in 17 countries: topotecan/ cyclophosphamide (TC), irinotecan/temozolomide (IT), gemcitabine/docetaxel (GD), and ifosfamide (IFOS). The primary objective is to identify the optimal regimen based on a balance between efficacy and toxicity. Martin G. McCabe, MB BChir, PhD, of the University of Manchester in the United Kingdom, presented the results on behalf of the investigators of the rEECur trial.
Results
Two hundred twenty patients 4 years or older and younger than 50 years with recurrent or refractory histologically confirmed ES of bone or soft tissue were randomized to receive GD (n=72) or TC, IT, or IFOS (n=148). Sixty-two GD patients and 123 TC/IT/IFOS patients were included in the primary outcome analysis. Patients were predominantly male (70%), with a median age of 19 years (range, 4 to 49). About two-thirds (67.3%) were post-pubertal. Most patients (85%) were primary refractory or experienced their first disease recurrence, and 89% had measurable disease.
Investigators assessed the primary outcome of objective response after 4 cycles of therapy and found 11% of patients treated with GD responded compared to 24% in the other 3 arms combined. When they subjected the data to Bayesian analysis, there was a 25% chance that the response rate in the GD arm was better than the response in Arm A, a 2% chance that it was better than Arm B, and a 3% chance that it was better than Arm C. Because this study was still blinded at the time of the presentation, investigators didn’t know which regimen constituted which arm. The probability that response favored GD, however, was low.
The investigators observed no surprising safety findings. Eighty-five percent of all patients experienced at least 1 adverse event. Most frequent grade 3‐5 events consisted of pneumonitis (50%, 60%), neutropenic fever (17%, 25%), and diarrhea (0, 12%) in GD and the combined 3 arms, respectively. Grade 3 events in the GD arm were lower than in the other 3 arms combined. There was 1 toxic death attributed to neutropenic sepsis in 1 of the 3 blinded arms.
Median progression-free survival (PFS) for all patients was approximately 5 months. Bayesian analysis suggested there was a low probability that GD was more effective than the other 3 arms: a 22% chance that GD was better than Arm A, a 3% chance that it was better than Arm B, and a 7% chance that it was better than Arm C. Bayesian analysis also suggested there was a probability that OS favored GD. Because the trial directs only the first 4 or 6 cycles of treatment and the patients receive more treatment after trial-directed therapy, investigators were not fully able to interpret this.
Data suggested GD is a less effective regimen than the other 3 regimens both by objective response rate and PFS, so GD has been dropped from the study. Investigators already had more than 75 evaluable patients in each of the 3 arms for the second interim analysis to take place. In a discussion following the presentation, Jayesh Desai, FRACP, of Peter MacCallum Cancer Centre in Melbourne, Australia, called this study a potentially practice-changing trial at this early stage, noting that the GD combination will be de-prioritized in practice based on these results.
SOURCE: McCabe MG, et al. J Clin Oncol 37, 2019 (suppl; abstr 11007)
The rEECur trial is sponsored by the University of Birmingham (UK) and received funding from the European Union’s Seventh Framework Programme under a grant agreement.
Dr. McCabe disclosed no conflicts of interest. Other authors disclosed consulting, advisory roles, or research funding from numerous pharmaceutical companies, including Lilly (gemcitabine) and Pfizer (irinotecan). Dr. Desai disclosed a consulting/advisory role and institutional research funding from Lilly.
Abemaciclib Meets Primary Endpoint in Phase 2 Trial of DDLS
The newer and more potent CDK4 inhibitor, abemaciclib, met its primary endpoint in the investigator-initiated, single-center, single-arm, phase 2 trial in patients with advanced progressive dedifferentiated liposarcoma (DDLS). Twenty-two patients (76%) achieved progression-free survival (PFS) at 12 weeks for a median PFS of 30 weeks. A subset of patients experienced prolonged clinical benefit, remaining on study with stable disease for over 900 days. The study (NCT02846987) was conducted at Memorial Sloan Kettering Cancer Center (MSKCC) in New York and Mark A. Dickson, MD, presented the results at ASCO.