Does Pembrolizumab Monotherapy Demonstrate Benefit in Rare Sarcomas?

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Pembrolizumab monotherapy induced responses in patients with rare sarcomas that varied by histotype, according to findings presented by Jean-Yves Blay, MD, at the ESMO Virtual Congress 2020 (Abstract 1619O).


Dr. Blay presented first results from a cohort of patients with rare sarcomas in the phase II, nonrandomized parallel-arm, open-label, multicenter AcSé Pembrolizumab study, which investigated the efficacy and safety of single-agent pembrolizumab in rare cancers.

The histotypes evaluated were all rare sarcomas with an incidence of less than 0.2 cases per 100,000 individuals per year. Eligible patients were aged > 18 years with an Eastern Cooperative Oncology Group performance status ≤ 1 and advanced disease that was resistant to standard treatment.

Pembrolizumab was administered at 200 mg intravenously as a 30-minute infusion on day 1 of every 21-day cycle for a maximum of 2 years to all participants. The primary endpoint of the study was the confirmed objective response rate according to Response Evaluation Criteria in Solid Tumors version 1.1, and secondary endpoints included clinical benefit rate, duration of response, progression-free survival, overall survival, and safety.

The 80 patients with rare sarcomas were classified according to histotype into five groups:

  • Chordoma (n = 24)
  • Alveolar soft-part sarcoma (ASPS; n = 13)
  • Desmoplastic small round cell tumor (DSRCT; n = 6)
  • Smarca4-malignant rhabdoid tumor (SMBT; n = 6)
  • Other histotypes (n = 31).

From July 2017 to February 2020, patients received a median of 5 cycles (range = 1–33) of pembrolizumab.  


Efficacy analysis of the overall patient population showed the best response was partial response, which was observed in 13 (16.25%) patients (95% confidence interval [CI] = 8.9%–26.2%). Stable disease was observed in 29 (36.25%) patients.

Response was found to be histotype-dependent, with the group of patients with SMBT showing the highest response rate and patients with other histotypes showing the lowest; three (50%) responses were observed in patients with SMBT, five (39%) in ASPS, one (17%) in DSRCT, two (8%) in chordoma, and two (6%) in other histotypes (P = .010).

Response was reflected in the survival rates; median progression-free survival was 5.7 months in patients with chordoma, 14 months in ASPS, 5 months in DSRCT, not reached in SMBT, and 2.7 months in the other histotypes group (P = .00016). At data cutoff, the 1-year progression-free survival rates in the respective histotype groups were 35%, 58%, 0%, 62.5%, and 8%.

Median overall survival was reached in three of the five groups; median overall survival was 20 months in the chordoma cohort, 7.4 months in the DSRCT cohort, and 5.4 months in the other histotype group. The 1-year overall survival rates were 72% in chordoma, 90% in ASPS, 50% in DSRCT, 83% in SMBT, and 40% in the group with other histotypes (P = .02).

Regarding the safety endpoint, trial discontinuation after receiving a median of four cycles was reported for 54 (67.5%) patients. Death occurred in 28 patients after receiving a median of three cycles; of these deaths, 27 were cancer-linked, and 1 was due to other causes.

Dr. Blay and colleagues concluded that pembrolizumab showed high levels of prolonged activity in selected subtypes of rare sarcomas. These sarcomas are not consistently associated with PD-L1 expression, high tumor mutational burden, cell infiltrates, or tertiary lymphoid structures. Translational research to understand the determinants of response is ongoing.

Disclosure: This UNICANCER study was funded by MSD. For full disclosures of the study authors, visit

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