benefit. More recent studies have used dacarbazine as the comparator arm in trials of novel therapies. Response rates obtained with dacarbazine in these studies have been less impressive. Dacarbazine continues to be listed in the NCCN and ESMO guidelines as an option for 2nd or later line chemotherapy. In addition, the current Australian guideline recommends the following: For patients who have been exposed to both doxorubicin and ifosfamide, dacarbazine is considered the next most active approved agent. It is also noteworthy that other regulatory authorities with similar standards to the TGA, such as the FDA and EMA, have accepted dacarbazine monotherapy as an acceptable comparator given their approvals for trabectedin and eribulin. As above, dacarbazine is registered in Australia for the treatment of STS. Overall it is considered that the sponsor’s choice of dacarbazine monotherapy as the comparator agent in the pivotal study is acceptable. Table 3: Published studies of dacarbazine monotherapy in STS Study Design Indication N Dacarbazine ORR Median Median regimen PFS OS Gottlieb Phase II STS 53 Various 17% - - 1976 Buesa Phase II STS 44 1200 mg/m2 18% - - – various 1991 Day 1 of a (95% 2nd line cycle CI: STS 14 1200 mg/m2 - 5 0% – various Day 1 of a mths 1996 Case 2nd line cycle series Zucali STS 40 800 mg/m2 on 7.5% 2 13 – various day 1; or 2008 mths mths Case 2nd line 400 mg/m2 on series days 1 and 2; or 300 mg/m2 on days 1, 2 and 3. 21-day cycle for all II STS 52 1200 mg/m2 4% 2 8.2 – RCT various Day 1 of a (95% mths mths Vs. 2nd line cycle CI: 2011 + Phase 173 1000 mg/m2 6.9% 1.5 12.9 III RCT
benefit. More recent studies have used dacarbazine as the comparator arm in trials of novel therapies. Response rates obtained with dacarbazine in these studies have been less impressive. Dacarbazine continues to be listed in the NCCN and ESMO guidelines as an option for 2nd or later line chemotherapy. In addition, the current Australian guideline recommends the following: For patients who have been exposed to both doxorubicin and ifosfamide, dacarbazine is considered the next most active approved agent. It is also noteworthy that other regulatory authorities with similar standards to the TGA, such as the FDA and EMA, have accepted dacarbazine monotherapy as an acceptable comparator given their approvals for trabectedin and eribulin. As above, dacarbazine is registered in Australia for the treatment of STS. Overall it is considered that the sponsor’s choice of dacarbazine monotherapy as the comparator agent in the pivotal study is acceptable. Table 3: Published studies of dacarbazine monotherapy in STS Study Design Indication N Dacarbazine regimen ORR Median PFS Median OS Gottlieb 1976 Phase II STS 53 Various 17% - - Buesa 1991 Phase II STS – various 2nd line 44 1200 mg/m2 Day 1 of a cycle 18% (95% CI: - - 1996 Case series STS – various 2nd line 14 1200 mg/m2 Day 1 of a cycle 0% - 5 mths Zucali 2008 Case series STS – various 2nd line 40 800 mg/m2 on day 1; or 400 mg/m2 on days 1 and 2; or 300 mg/m2 on days 1, 2 and 3. 21-day cycle for all 7.5% 2 mths 13 mths 2011 II RCT Vs. + STS – various 2nd line 52 1200 mg/m2 Day 1 of a cycle 4% (95% CI: 2 mths 8.2 mths Phase III RCT 173 1000 mg/m2 6.9% 1.5 12.9
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