SBRT with ipilimumab and nivolumab to metastatic MSS colorectal and pancreatic cancer: A pooled analysis of four prospective phase II trials.

Authors

null

Hannah Johnson Roberts

Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA

Hannah Johnson Roberts , Jessica Seidenberg , Beow Y. Yeap , Julie L. Koenig , Aparna Raj Parikh , Jeffrey William Clark , David P. Ryan , Jill N. Allen , Colin D. Weekes , Lawrence Scott Blaszkowsky , Priyadarshini Pathak , Lorraine C. Drapek , Leilana Ly , Theodore S. Hong , Jennifer Yon-Li Wo

Organizations

Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, Department of Medicine, Division of Hematology & Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, Massachusetts General Hospital, Boston, MA, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA

Research Funding

No funding sources reported

Background: The role of immunotherapy (IO) in microsatellite stable (MSS) pancreatic and colorectal cancer is limited. Stereotactic body radiation therapy (SBRT) is increasingly used in the limited metastatic setting, however its use with IO remains an area of investigation for both target response and overall systemic response. Here we evaluate the local failure rate of irradiated target lesions with and without IO. Methods: We pooled four prospective phase II single-arm studies of patients with metastatic MSS colorectal or pancreatic cancer treated with SBRT alone or with IO. Those in the first study (NCT01239381) received ablative liver SBRT to a maximum biologically effective dose (BED) of 48-100 Gy. Patients in the remaining studies received low dose SBRT to liver, lung, or nodal metastases with 24 Gy in 3 fractions to a BED of 43.2 Gy in combination with Ipilimumab and Nivolumab during the first (NCT04361162, NCT04575922) or second (NCT03104439) cycles. Local failure rates at the time of first progression were estimated by the cumulative incidence with non-target progression only and death as competing risks and compared using Gray’s test. The best response at the target was measured with the RECIST 1.1 criteria using the largest reduction in target size during follow up. Fisher’s exact test was used to compare objective response (ORR) and disease control rates (DCR), while the Wilcoxon rank sum test was performed to compare target size and percentage of tumor reduction. Results: Across all four studies there were 154 evaluable patients including 50 who received ablative SBRT and 104 patients who received low dose SBRT with IO. There were 92 patients with colorectal and 62 with pancreatic cancer. Median target size was 3.7 cm in the ablative SBRT group and 2.8 cm in the IO group (P=0.04). The 6-month, 1-year, and 2-year local failure rates were 10%, 18%, and 20% respectively following ablative SBRT and 24%, 25%, and 26% following low dose SBRT with IO (P=0.32). The ORR was 50.0% with SBRT alone and 23.1% with the addition of IO (P=0.001). There was no significant difference in the DCR (80.0% vs. 68.3%, P=0.18). The percent decrease in size was significantly higher in those with ablative SBRT (median -53.0% vs. -10.6%, p=0.02). There was no difference in the percent tumor response with respect to primary tumor type (P=0.13), KRAS (P=0.11) or TP53 (P=0.27) status. Conclusions: Despite the use of low dose SBRT with immune checkpoint inhibitors, there was no significant difference in local failure rates compared to ablative SBRT. Ablative SBRT dosing yielded a significantly higher depth of response. As clinical and preclinical studies suggest liver metastases are less responsive to IO, understanding dose and fractionation schemas for optimal local control is critical. Further studies are needed to explore the radiation dose with regards to local control when delivered with IO.

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Abstract Details

Meeting

2024 ASCO Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Cancers of the Esophagus and Stomach and Other Gastrointestinal Cancers

Track

Esophageal and Gastric Cancer,Other GI Cancer

Sub Track

Therapeutics

Citation

J Clin Oncol 42, 2024 (suppl 3; abstr 752)

DOI

10.1200/JCO.2024.42.3_suppl.752

Abstract #

752

Poster Bd #

M7

Abstract Disclosures