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: