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AIM regimen extends PFS, OS in soft tissue sarcoma
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WAILEA, Hawaii — The combination of doxorubicin, ifosfamide and mesna significantly improved outcomes among patients with advanced soft tissue sarcomas compared with olaratumab plus doxorubicin, according to retrospective study results presented at Connective Tissue Oncology Society Annual Meeting.
“Prospective trials comparing [the two regimens] may be warranted given the survival differences observed in this retrospective single-center review,” Kathryn J. Hammer, PharmD, BCOP, BCPS, of the department of pharmacy at University of Washington, and colleagues wrote.
Doxorubicin, ifosfamide and mesna — a regimen commonly known as AIM — had been a first-line treatment option for patients with advanced unresectable or metastatic soft tissue sarcoma.
Is use declined after a survival benefit compared with single-agent doxorubicin could not be shown. However, it may be reserved for cases when tumor shrinkage is the primary goal of therapy, according to study background.
Hammer and colleagues conducted their study to compare survival, response and tolerability among patients with advanced soft tissue sarcoma who underwent treatment with AIM vs. olaratumab (Lartruvo, Eli Lilly) plus doxorubicin.
Researchers identified 117 adults with unresectable or metastatic soft tissue sarcoma treated with one of these two regimens from Jan. 1, 2013, through Aug. 30, 2017, at Seattle Cancer Care Alliance/University of Washington Medical Center.
The final analysis included 30 patients who received treatment in 21-day cycles.
Seventeen patients received AIM, which consisted of doxorubicin 25 mg/m2 IV over 24 hours on days 1 to 3 for three doses; ifosfamide 2 g/m2 IV over 4 hours on days 1 to 5 for five doses, and mesna 400 mg/m2 IV given pre-ifosfamide, as well as 4 and 8 hours after ifosfamide, for 15 doses. Thirteen patients received doxorubicin 75 mg/ m2 IV over 10 to 15 minutes on day 1, plus olaratumab 15 mg/kg IV over 60 minutes on days 1 and 8.
Treatment groups were balanced with regard to age, sex, race, ECOG status, histological type and extent of disease.
Patients assigned AIM achieved significantly longer median OS (18.5 months vs. 7.9 months; HR = 0.08; 95% CI, 0.02-0.38) and PFS (18.5 months vs. 8.1 months; HR = 0.87; 95% CI, 0.01-0.89). They also remained on treatment longer (median duration, 127 days vs. 52 days).
Seven patients (41%) treated with AIM achieved clinician-reported response, compared with six (46%) assigned doxorubicin and olaratumab.
Seventeen patients — 10 (59%) treated with AIM and seven (54%) treated with doxorubicin and olaratumab — required dose reductions.
Patients who received AIM experienced higher rates of anemia (all grade, 88% vs. 77%; grade 3/grade 4, 41% vs. 8%), and thrombocytopenia (all grade, 76% vs. 62%; grade 3/grade 4, 41% vs. 8%), as well as neurotoxicities (24% vs. 0%), renal toxicity (24% vs. 0%) and cardiac toxicity (18% vs. 0%).
Two patients treated with AIM proceeded to surgical resection.
Shorter follow-up period and exposure to prior lines of chemotherapy for patients treated with doxorubicin and olaratumab may have confounded OS and PFS results, researchers wrote. Other limitations included a small sample size, the study’s single-center design and its short duration, they added.
Results of the phase 3 ANNOUNCE trial — designed to confirm a survival benefit with olaratumab plus doxorubicin vs. doxorubicin alone — are eagerly awaited, Hammer and colleagues wrote. – by Mark Leiser
For more information:
Hammer KJ, et al. Poster 286. Presented at: Connective Tissue Oncology Society Annual Meeting; Nov. 8-11, 2017; Maui.
Disclosures: The authors report no relevant financial disclosures.