PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group

Borchmann, Peter; Goergen, Helen; Kobe, Carsten; Lohri, Andreas; Greil, Richard; Eichenauer, Dennis A.; Zijlstra, Josée M.; Marková, Jana; Meißner, Julia; Feuring‐Buske, Michaela; Hüttmann, Andreas; Dierlamm, Judith; Soekler, Martin; Beck, Hans Joachim; Willenbacher, Wolfgang; Ludwig, Wolf Dieter; Pabst, Thomas; Topp, Max S.; Hitz, Felicitas; Bentz, Martin; Keller, Ulrich; Kühnhardt, Dagmar; Ostermann, Helmut; Schmitz, Norbert; Hertenstein, Bernd; Aulitzky, Walter E.; Maschmeyer, Georg; Vieler, Tom; Eich, Hans Theodor; Baues, Christian; Stein, Harald; Fuchs, Michael; Kuhnert, Georg; Diehl, Volker; Dietlein, Markus; Engert, Andreas

doi:10.1016/s0140-6736(17)32134-7

Cited by 284 publications

(259 citation statements)

References 26 publications

Supporting

Mentioning

241

Contrasting

Unclassified

Order By: Relevance

“…5,6 Recent studies suggest that response-adapted therapy guided by interim positron-emission tomography (PET) with 18 F-fluorodeoxyglucose can provide a more individualized treatment approach, in which treatment intensity is de-escalated or intensified depending on the early response to treatment. 7,8 Efforts are also being made to incorporate new drugs into established backbone regimens to improve efficacy and reduce toxicity. 9 …”

mentioning

confidence: 99%

Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma

et al. 2018

View full text Add to dashboard Cite

BACKGROUND Brentuximab vedotin is an anti-CD30 antibody–drug conjugate that has been approved for relapsed and refractory Hodgkin’s lymphoma. METHODS We conducted an open-label, multicenter, randomized phase 3 trial involving patients with previously untreated stage III or IV classic Hodgkin’s lymphoma, in which 664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The primary end point was modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary end point was overall survival. RESULTS At a median follow-up of 24.9 months, 2-year modified progression-free survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [CI], 78.7 to 85.0) and 77.2% (95% CI, 73.7 to 80.4), respectively, a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% CI, 0.60 to 0.98; P = 0.03). There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.72 [95% CI, 0.44 to 1.17]; P = 0.19). All secondary efficacy end points trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%). Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit. Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD. Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity. CONCLUSIONS A+AVD had superior efficacy to ABVD in the treatment of patients with advanced-stage Hodgkin’s lymphoma, with a 4.9 percentage-point lower combined risk of progression, death, or noncomplete response and use of subsequent anticancer therapy at 2 years. (Funded by Millennium Pharmaceuticals and Seattle Genetics; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.)

show abstract

mentioning

confidence: 99%

Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In the pre‐positron emission tomography (PET) era trials in adult HL (Johnson et al , ; Borchmann et al , ; Gordon et al , ) found a significant benefit to the use of RT as part of initial therapy. More recently, the GITIL/FIL HD 0607 trial found no significant benefit to RT among patients with nodal masses ≥5 cm who had a negative PET scan after two and four cycles of ABVD (Casasnovas et al , ), and adult HL protocols incorporating escalated dose BEACOPP have reported 5‐year progression‐free survival (PFS) rates >85% with limited or no routine use of RT (Borchmann et al , ). These findings suggest that PET‐computed tomography (CT) may be utilized to tailor or avoid RT for the majority of HL patients who achieve a rapid metabolic response, when chemotherapy is sufficiently intensive.…”

Section: Primary Prevention To Close the Survivorship Gapmentioning

confidence: 99%

Closing the survivorship gap in children and adolescents with Hodgkin lymphoma

2019

View full text Add to dashboard Cite

Summary The treatment of Hodgkin lymphoma (HL) is one of early success. However, disease‐free survival (DFS) does not reflect latent organ injury and its impact on health status and well‐being beyond 5 years. In fact, we are at a crossroads, in terms of needing individualized approaches to maintain DFS, while minimizing late effects and preserving health‐related quality of life (HRQoL). Premature morbidity and mortality translate to a high societal cost associated with the potential number of productive life years ahead in this population who are young at diagnosis. The discordance between short‐term lymphoma‐free survival and long‐term health and HRQoL creates a “survivorship gap” which can be characterized for individuals and for subgroups of patients. The current review delineates contributors to compromised outcomes and health status in child and adolescent (paediatric) HL and frames the survivorship gap in terms of primary and secondary prevention. Primary prevention aims to titrate therapy. Secondary prevention entails strategies to intervene against late effects. Bridging the survivorship gap will be attained with enhanced knowledge of and attention to biology of the tumour and microenvironment, host genetic factors, HRQoL and sub‐populations with disparate outcomes.

show abstract

“…Patients with negative interim FDG‐PET results after 2 cycles of eBEACOPP treated with standard therapy (6× or 8× eBEACOPP) had a 5‐year PFS of 90·8%, whereas patients with negative interim FDG‐PET results treated with de‐escalated therapy (4× eBEACOPP) had a 5‐year PFS of 92·2%. Borchmann et al () recommended interim FDG‐PET adapted therapy in order to reduce the number of therapy cycles and associated morbidity in patients with negative interim FDG‐PET results.…”

Section: Current Evidence On the Proportion Of False‐positives On Intmentioning

confidence: 99%

“…Note that patients with positive and negative interim FDG‐PET results had a similar outcome when treated with 6× or 8× BEACOPP (5‐year PFS of 89·7% and 90·8%, respectively), and that there was no experimental arm in which treatment de‐escalation was applied in patients with positive interim FDG‐PET results. Furthermore, as noted by the authors themselves, so far there have been no other studies on treatment adaptation on the basis of interim FDG‐PET in patients treated with BEACOPP (Borchmann et al , ). The lack of an experimental arm applying treatment de‐escalation in patients with positive interim FDG‐PET results in the study by Borchmann et al () and the lack of a comparative historical cohort applying treatment de‐escalation in patients with positive interim FDG‐PET results underline that no conclusion, even not yet a presumption, can be made on whether treatment de‐escalation is more effective in patients with negative versus those with positive interim FDG‐PET results.…”

Section: Current Evidence On the Proportion Of False‐positives On Intmentioning

confidence: 99%

“…Furthermore, as noted by the authors themselves, so far there have been no other studies on treatment adaptation on the basis of interim FDG‐PET in patients treated with BEACOPP (Borchmann et al , ). The lack of an experimental arm applying treatment de‐escalation in patients with positive interim FDG‐PET results in the study by Borchmann et al () and the lack of a comparative historical cohort applying treatment de‐escalation in patients with positive interim FDG‐PET results underline that no conclusion, even not yet a presumption, can be made on whether treatment de‐escalation is more effective in patients with negative versus those with positive interim FDG‐PET results. The fact that patients with positive interim FDG‐PET scans had a favourable prognosis after standard eBEACOPP therapy (5‐year PFS 89·7%) even suggests that treatment de‐escalation may also be feasible in this subgroup of patients.…”

Section: Current Evidence On the Proportion Of False‐positives On Intmentioning

confidence: 99%

See 1 more Smart Citation