Abstract
Background: In this decade the treatment of advanced sarcoma has seen many highs and lows in
terms of successful trials and failed trials. This is possible due to great collaborations,
newer therapies and histology focused trials. Methods: In ASCO 2019 many sarcoma trials were presented and we chose 3 challenging clinical
trials that widen our perspective on soft tissue sarcoma. We have critically analyzed
the data and have discussed the implications of these trials on current practice.
First trial was ANNOUNCE trial which was done to confirm the efficacy of olaratumab
after its dramatic success in advanced soft tissue sarcoma in a phase 2 trial. Another
trial STRASS trial, which was unique because of being first successfully conducted
randomized trial addressing preoperative radiotherapy in retroperitoneal soft tissue
sarcoma. Third trial was phase 2 trial SARC 028 trial exploring the role of immunotherapy
in pleomorphic undifferentiated sarcoma and liposarcoma subgroup. Result: ANNOUNCE trial failed to show OS benefit in olaratumab/doxorubicin arm as compared
to doxorubicin/placebo arm . Based upon this FDA has revoked the approval of olaratumab
leading to nihilism and disappointment amongst oncologists. In STRASS trial failed
to meet the primary end point though there was a benefit in the liposarcoma subgroup
in terms of abdominal recurrence free survival. There are several reasons that this
trial might have failed. First, RPSs are not homogeneous population. RPSs might behave
very differently as per the histopathology ranging from well differentiated LPS to
leiomyosarcoma. Since the event rate in well-differentiated liposarcoma might happen
late, the median follow-up of 43 months might not be sufficient. In SARC trial ORR
in pleomorphic undifferentiated sarcoma (PUS) cohort was 9/40 (22.5%), while response
rates in liposarcoma cohort were 4/39 (10.2%). There was poor correlation between
the response and the tumor cells’ PD-L1 positivity. Simultaneously, we must not take
for granted the role of pembrolizumab in PUS as the previous study (PEMBROSARC) had
also showed dismal outcomes with immunotherapy. Conclusion: In this paper we discuss the intricacies of these trials and how they affect the
rapidly changing landscape in advanced soft tissue sarcoma.
Key words
ASCO - Soft tissue sarcoma - STS - Leiomyosarcoma - Relapse - LPS - PUS - Olaratumab
- Pembrolizumab
