Radiation Biology

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SU_38_2386 - Association Between Radiation Therapy and PD-1 Inhibitors

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Association Between Radiation Therapy and PD-1 Inhibitors
S. Patel1, N. Abdallah1, M. Nagasaka2, S. Kim3, H. E. Kim2, and A. Sukari2; 1Detroit Medical Center, Wayne State University, Detroit, MI, 2Karmanos Cancer Institute, Detroit, MI, 3Wayne State University, Detroit, MI

Purpose/Objective(s): It has been demonstrated that tumor cells are able to escape immune regulation through the expression of PD-L1 in the tumor microenvironment incited by inflammation caused by ionizing radiotherapy. The use of PD-1/PDL-1 checkpoint inhibitors has been postulated as a mechanism to bypass the antitumor immunity, and allow for immune-mediated tumor death. We investigated the objective response with progressive or stable disease (PD+SD), and survival when combining PD-1/PDL-1 inhibitors and radiotherapy ≤6 months of administration.

Materials/Methods: Our Institution’s pharmacy database was used to collect data on patients who received ≥1 dose of PD-1 inhibitors (Nivolumab or Pembrolizumab) before August 31, 2016. Patients who received radiotherapy ≤6 months of their PD-1 inhibitor treatment were selected for evaluation. Pretreatment and post treatment PET scans were evaluated using the RECIST criteria for objective response. Follow up imaging was used to determine first date of progression. Univariate and multivariate analyses were performed to evaluate if radiotherapy ≤6 months of starting PD-1 inhibitors affected disease response. Patients treated with intracranial radiotherapy were evaluated separately.

Results: Of the 87 patients who received at least one dose of PD-1 inhibitor, 38 had radiotherapy ≤6 months, 22 had radiotherapy >6 months from treatment, and 27 had no radiotherapy. Patients receiving radiotherapy ≤6 months of PD-1 inhibitor had a higher risk of progressive or stable disease (p≤0.012), and had a lower progression free suvival as well (p≤0.004). There was no difference in the overall surivival between the groups. The findings remained statistically significant when adjusting for intracranial radiotherapy. Table 3. Univariable and multivariable logistic regression analysis of risk factors on objective responses (PD+SD)
N Univariable analysis Multivariable analysis
OR (95% CI) Signif. OR (95% CI) Signif.
Radiation
<= 6 mons 38 Reference Reference
> 6 mons 22 0.061 (0.003, 0.384) 0.012 0.021 (0.001,0.223) 0.008
No 27 0.121 (0.006, 0.822) 0.062 0.031 (0.001,0.433) 0.028
Intracranial radiation
No 64 Reference Reference
Yes 23 1.319 (0.357, 6.357) 0.697 0.156 (0.007,1.491) 0.140

Conclusion: There was a higher likelihood of no response (PD+SD) in patients treated with radiotherapy and PD-1 inhibitor ≤6 months compared to those treated >6 months, or with those not treated with radiotherapy. Our results suggest that there is no effect to increase the responses by combining modalities. There was no difference in overall survival, which suggests there is no increased risk of fatal toxicity in combining the two therapies within a time interval of 6 months. Radiation was also likely used as a salvage approach in areas of progression or palliation, which may be why overall survival was not affected.

Author Disclosure: S. Patel: None. N. Abdallah: None. S. Kim: None. A. Sukari: None.

Suketu Patel, MD, BS, MPH

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