As reported in the Journal of Clinical Oncology by Casasnovas et al, final results of the phase III AHL2011 Lymphoma Association Study showed continued similarity of progression-free and overall survival over long-term follow-up with positron-emission tomography (PET)-based de-escalation of chemotherapy vs standard treatment in previously untreated patients with advanced Hodgkin lymphoma. Interim PET findings were prognostic for outcomes in the entire patient population.
Study Details
In the open-label trial, 823 patients aged 16 to 60 years from sites in Belgium and France were randomly assigned to standard treatment with six cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone; n = 413) or PET-driven therapy (n = 410). The PET-driven group received two cycles of BEACOPP; those with PET-negative findings after two cycles (PET2) received four cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), and those with PET2-positive findings received four additional cycles of BEACOPP. PET performed after four cycles of chemotherapy (PET4) had to be negative for patients to complete planned treatment. All study patients were to undergo PET2 and PET4.
At the previously reported primary analysis, the PET-driven de-escalation strategy was associated with similar progression-free survival (primary endpoint) and overall survival, as well as reduced early toxicity, compared with standard treatment.
Key Findings
Median follow-up was 5.6 years (95% confidence interval [CI] = 5.5–5.7 years). In the intent-to-treat population, 5-year progression-free survival was 86.7% in the PET-driven group vs 87.5% in the standard group (hazard ratio [HR] = 1.07, 95% CI = 0.74–1.57, P = .67; P = .0037 for noninferiority) and 5-year overall survival was 97.7% in both groups (HR = 1.012, 95% CI = 0.50–2.10, P = .53).
Among 367 patients in the PET-driven group vs 372 in the standard group in the per-protocol population, 5-year progression-free survival was 86.5% v 88.1% (HR = 1.01, 95% CI = 0.75–1.66, P = .75; P = .015 for noninferiority) and 5-year overall survival was 96.3% vs 97.1% (HR = 1.20, 95% CI = 0.55–2.60, P = .69).
Among PET2-negative patients in the PET-driven group treated with two cycles of BEACOPP plus four cycles of ABVD vs those in the standard group who received six cycles of BEACOPP, 5-year progression-free and overall survival rates were 90.5% vs 89.9% and 97.8% vs 97.6%. Among PET2-positive patients who received six cycles of BEACOPP in the PET-driven vs standard group, respective outcomes were 68.2% vs 73.5% and 92.0% vs 93.7%.
In the whole cohort, interim PET assessment predicted 5-year progression-free survival independent of international prognosis score, with rates of 92.3% in PET2-negative/PET4-negative patients, 75.4% in PET2-positive/PET4-negative patients (HR = 3.26, 95% CI = 1.83–5.77, P < .0001), and 46.5% in PET4-positive patients (HR = 12.4, 95% CI = 7.31–19.51, P = .0001).
Similarly, 5-year overall survival was 98.2% in PET2-negative/PET4-negative patients, 93.5% in PET2-positive/PET4-negative patients (HR = 3.3, 95% CI = 1.07–10.1, P = .036) and 91.9% in PET4-positive patients (HR = 3.76, 95% CI = 1.07–13.18, P = .038).
Second primary malignancies occurred in 9 patients (2.2%) in the PET-driven group vs 13 patients (3.2%) in the standard group.
The investigators concluded, “The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.”
René-Olivier Casasnovas, MD, of the Department of Hematology, University Hospital F. Mitterrand and Inserm UMR, Dijon, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the French government Programme Hospitalier de Recherche Clinique 2010. For full disclosures of the study authors, visit ascopubs.org.
