Immunotherapy for Angiosarcoma: Promising Results for Scalp and Face Tumors

Photo of sarcoma, magnification 200x, photo under microscope: © Chutima - stock.adobe.com

While immunotherapy has become a mainstay of treatment for various types of cancer, it has been less successful in treating sarcomas. The Alliance AO91902 trial (NCT04339738) sought to investigate whether adding immunotherapy to chemotherapy would improve outcomes for patients with advanced angiosarcoma.

Findings from the first arm of the phase 2 study were reported in 2023 and showed that cabozantinib (Cabometyx) plus nivolumab (Opdivo) led to notable antitumor activity with good tolerability in patients with taxane-pretreated advanced angiosarcoma.¹ The overall response rate (ORR) was 62% (95% CI, 38%-82%) with a median progression-free survival (PFS) of 9.6 months (range, 5.3-not reached [NR]), and overall survival (OS) of 20.5 months (range, 14.4-NR).

Findings from the second arm of the study were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting but were less promising. Adding nivolumab alone to paclitaxel did not significantly improve PFS compared with paclitaxel alone. The median PFS for paclitaxel/nivolumab was 7.2 months (range, 5.3-17), and 8.3 months (range, 4.0-18) for paclitaxel alone (HR, 1.01; 95% CI, 0.55-1.9), P =.96).²

There was more benefit for patients with scalp and face angiosarcoma, with a median PFS of 16 months (95% CI, 10-NR) with paclitaxel/nivolumab and 8.3 months (95% CI, 3.7-NR) with paclitaxel. Further, the median OS was 18 months (range, 13-NR) with paclitaxel/nivolumab compared with 23 months (range, 15-NR) with paclitaxel (HR 1.3; 95%CI, 0.63-2.7; P =.48). The ORR for paclitaxel/nivolumab was 33% and 73% in patients with scalp or face angiosarcoma. 

While the combination did not demonstrate a clear benefit over paclitaxel alone in the general angiosarcoma population, further investigation is warranted for scalp/face angiosarcoma. Additional analyses are ongoing to explore the impact of treatment on patient-reported outcomes.

In an interview with Targeted Oncology^TM, Juneko Grilley-Olson, MD, associate professor in medicine at the Duke University School of Medicine and member of the Duke Cancer Institute, discussed this study and the greater importance of clinical trials in sarcoma.

Juneko Grilley-Olson, MD

Targeted Oncology: Immunotherapy has shown promise in many types of cancerbut not as much in sarcoma. Can you explain why this is?

Grilley-Olson: Sarcomas in general are a wide collection of very rare cancers. There are more than 100 different histologic subtypes of soft tissue sarcomas in the category of rare cancers, so there are a lot of different subsets, many of which have very small incidents individually. One of the things that the entire sarcoma community has struggled with for many years is trying to efficiently complete trials. But now, we are trying to focus more on individual disease subtypes. Immunotherapies across the wide swath of sarcomas have been less promising, with certain subsets showing some promise, or the early signals being most prominent in undifferentiated pleomorphic sarcomas. But perhaps the most sensitive areas of rare subtype called alveolar soft part sarcoma. Angiosarcomas are another area that have had some early signals of efficacy in some of the early preclinical work. There have been some groups that demonstrated that the immune signature [of angiosarcomas] looks very much like ultraviolet damage like melanomas. That led to the thought that angiosarcomas may also be a more immune-sensitive phenotype.

Can you explain the goal of the study and what it evaluated?

The Alliance AO91902 was a study that had 2 main portions. Last year, we presented the data for cabozantinib/nivolumab in patients with taxane-pretreated angiosarcomas. There is a single-arm phase 2 study with an overall response rate of 59%, which is tremendously higher than we have seen in prior studies. That was an exciting outcome.

This year, we presented the randomized portion in patients that are taxane-naive. Patients were randomized to receive paclitaxel plus or minus nivolumab. In this portion, the primary outcome was progression-free survival. In an unselected angiosarcoma patient population, everyone could not have received prior taxanes, but could have received other lines of therapy. A small number of received doxorubicin-based or intersegment-based prior chemotherapies. Most in this cohort were had locally advanced or metastatic angiosarcomas.

We saw progression-free survival of 8 months in the paclitaxel monotherapy arm which outperformed any historic controls. The study did not meet his primary endpoint of an improvement of 3 months from paclitaxel to the combination with a trend toward benefit. In the scalp/face subpopulation there, we saw a doubling of overall survival from 8.3 to 16 months, and it was not powered to detect a significant difference. But it was a suggestion of a benefit in that particular population. We are still looking at the data trying to understand the implications of this negative outcome and where to go from here.

Do you foresee any next steps testing any other types of immunotherapies in combination with taxanes or other combinations in this patient group?

We are certainly thinking about the next steps. I think the most compelling data was presented at ASCO 2023 with cabozantinib/nivolumab. We are thinking more about platforms somewhat more analogous to that. The most promising data that had [was] a progression-free survival of over 9 months. The question is where to go from here with that, probably moving that to be randomized in combination vs standard-of-care chemotherapy. 

The part that was a credit to the sarcoma community and the patients, [and] the rapid rate that this trial accrued. This trial, at times, was the fastest accruing trial within the Alliance network. With a rare cancer, it shows that patients are there. We can get the trial done, and it is not something that should not be studied just because it is a rare cancer.

REFERENCES:

1. Grilley-Olson J, Allred J, Schuetze S, et al.A multicenter phase II study of cabozantinib + nivolumab for patients (pts) with advanced angiosarcoma (AS) previously treated with a taxane (Alliance A091902).J Clin Oncol.2023;41: 11503.doi:10.1200/JCO.2023.41.16_suppl.11503

2. Grilley-Olson J, Allred J, Schuetze S, et al. Alliance A091902: A multicenter randomized phase II trial of paclitaxel (P) with or without nivolumab (N) in patients (pts) with advanced angiosarcoma (AS).J Clin Oncol.2024;42(suppl 16):abstr 11514. doi:10.1200/JCO.2024.42.16_suppl.11514