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CC BY-NC-ND 4.0 · South Asian J Cancer 2019; 08(04): 258-259
DOI: 10.4103/sajc.sajc_215_19
ORIGINAL ARTICLE: Sarcomas and Skin Cancer

Advances in soft-tissue sarcoma – There are no mistakes, only lessons to learn!

Sameer Rastogi
Department of Medical Oncology, New Delhi
,
Parisa Manasa
Sachin Sarcoma Society, New Delhi
,
Aditi Aggarwal
Department of Radiation Oncology, AIIMS, NCI, Jhajjar, Haryana
,
Kaushal Kalra
Department of Medical Oncology, New Delhi
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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


Publication History

Article published online:
14 December 2020

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  • References

  • 1 Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: An open-label phase 1b and randomised phase 2 trial. Lancet 2016;388:488-97.
  • 2 Tap WD, Wagner AJ, Papai Z, Ganjoo KN, Yen CC, Schoffski P, et al. Announce: A randomized, placebo (PBO)-controlled, double-blind, phase (Ph) III trial of doxorubicin (dox) + olaratumab versus dox + PBO in patients (pts) with advanced soft tissue sarcomas (STS). J Clin Oncol 2019;37 18 Supp l:LBA3.
  • 3 Assessment of the Clinical Benefit of Cancer Drugs Receiving Accelerated Approval | Oncology | JAMA Internal Medicine | JAMA Network. Available from: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2733561 [Last accessed on 2019 Jul 09].
  • 4 Bonvalot S, Gronchi A, Pechoux CL, Swallow CJ, Dirk C, Strauss, et al. STRASS (EORTC 62092): A phase III randomized study of preoperative radiotherapy plus surgery versus surgery alone for patients with retroperitoneal sarcoma. J Clin Oncol 2019;37:11001. Available from: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.11001. [Last accessed on 2019 Aug 30].
  • 5 Nussbaum DP, Rushing CN, Lane WO, Cardona DM, Kirsch DG, Peterson BL, et al. Preoperative or postoperative radiotherapy versus surgery alone for retroperitoneal sarcoma: A case-control, propensity score-matched analysis of a nationwide clinical oncology database. Lancet Oncol 2016;17:966-75.
  • 6 Dingley B, Fiore M, Gronchi A. Personalizing surgical margins in retroperitoneal sarcomas: An update. Expert Rev Anticancer Ther 2019;19:613-31.
  • 7 Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): A multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 2017;18:1493-501.
  • 8 Burgess MA, Bolejack V, Schuetze S, Van Tine BA, Attia S, Riedel RF, et al. Clinical activity of pembrolizumab (P) in undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated/pleomorphic liposarcoma (LPS): Final results of SARC028 expansion cohorts. J Clin Oncol 2019;3715 supp l:11015.
  • 9 Toulmonde M, Italiano A. PD-1 inhibition in sarcoma still needs investigation. Lancet Oncol 2018;19:e6.