Improved Survival in Sarcoma Patients: Key Insights on Immunotherapy Sequencing

A team from the University of Texas MD Anderson Cancer Center reiterates the importance of continuing to evaluate how to best sequence radiation therapy (RT) and systemic therapies, with current study findings that show improved progression-free survival (PFS) among a group of 36 patients with pleomorphic sarcomas who received immune checkpoint blockade (ICB).

For this analysis, patients were identified using MD Anderson’s pharmacy database with records of ipilimumab (n = 2), nivolumab (n = 5), durvalumab (n = 11), tremelimumab (n = 11), atezolizumab (n = 2), and pembrolizumab (n = 14) use. Their median age at treatment initiation was 52 (range, 22-79) years, and 34% were female patients.

The findings of this retrospective observational study, published in Cancers (Basel), are the results of an investigation of survival outcomes among patients diagnosed with advanced or metastatic undifferentiated pleomorphic sarcomas (UPS; n = 26) or other high-grade sarcomas (“other”; n = 10) and treated with FDA-approved ICB therapies between January 1, 2015, and January 2, 2023.¹ This type of immunotherapy works by preventing the binding of checkpoint and partner proteins, thereby allowing T cells to continue their work of attacking and killing cancer cells.²

In this small study, the most common tumor site was an extremity or the Trunk | Image Credit: VitaliiVodolazskyi-stock.adobe.com

“UPS are amongst the most common subtypes of soft-tissue sarcomas,” the study authors wrote.¹ “Few real-world data on the use of ICB in UPS patients and other high-grade pleomorphic STS patients are available.” They added that previous research has identified UPS as being more sensitive to ICB regimens.

The most common overall Eastern Cooperative Oncology Group performance status score was 1 in 64%, meaning patient physical activity limit was restricted but they remained ambulatory.³ Those with UPS had a higher body mass index vs those with other high-grade sarcomas, at 31 kg/m² vs 26 kg/m², but their largest tumor size was still smaller (5.3 cm vs 6.7 cm), fewer patients had evidence of lung metastasis (69% vs 80%) or liver metastasis (8% vs 20%), and prior to ICB, they had fewer total lines of systemic therapy (2 vs 4) and fewer surgical resections (1 vs 2).¹ Sixty-five percent of the UPS group and 50% of the “other” cohort had a history of radiotherapy before ICB.

In the UPS cohort, the most common tumor site was an extremity (46% vs 38% with a trunk location and 16% with an “other” location [abdomen, heart, lumbar spine]) and in the “other” cohort, the trunk was the most common site (50% vs 30% with an extremity location and 20% with an “other” location).

Over an overall median follow-up of 8.8 months, 58% of patients had disease progression as their best treatment response, followed by 25% with stable disease (SD), 6% with a partial response (PR), and 3% with a complete response (CR). For the 33 patients who had an evaluable response by imaging, the clinical benefit rate was 30.3% and the overall response rate was 9.1%. Median PFS was 2.92 months following ICB, with 46% and 32% of patients at 3 and 6 months, respectively, achieving this treatment milestone; this was shorter in the UPS group vs the “other” group (2.9 vs 3.8 months).

Univariate analysis linked ICB combination to significantly shorter PFS (2.3 months) vs standalone treatment (9.2 months). Sarcoma histology, previous lines of systemic therapy, and previous RT were not linked to impact on PFS. However, among patients with a best response to ICB recorded, those who had a PR/CR or SD had median PFS of 40.7 months and 5.6 months, respectively, vs 2.2 months in patients who did not respond to ICB (P = .0012). Multivariate analysis showed that only previous RT (P = .0019) and type of ICB (P = .036) were independently associated with shorter PFS.

Median overall survival (OS) was 12.9 months for the entire study population, and at 12 months and 24 months after ICB initiation, 53% and 29% of patients, respectively, had achieved this outcome. This was also longer in the “other” group vs the UPS group, at 15 months and 12.9 months, respectively.

Only 4 patients discontinued treatment due to toxicities.

The study authors noted that because their study population was small, heterogeneous and from a single medical center, there is a high possibility of significant bias in their findings, no causality can be inferred, and they could not identify strong predictors of response.

“This study highlights a critical need for the identification of biomarkers of response to ICB for patients with sarcomas,” they concluded. “This highlights a challenge in deriving data from real-world studies beyond clinical trials but invites further investigation into potential predictors of response.”

References

1. Nasr LE, Zoghbi M, Lazcano R, et al. High-grade pleomorphic sarcomas treated with immune checkpoint blockade: the MD Anderson Cancer Center experience. Cancers (Basel). 2024;16(9):1763. doi:10.3390/cancers16091763

2. Immune checkpoint inhibitors. National Cancer Institute. Accessed May 13, 2024. https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors

3. ECOG performance status scale. ECOG-ACRIN Research Group. Accessed May 13, 2024.https://ecog-acrin.org/resources/ecog-performance-status/