Main Session

Sep 28

PQA 02 - Lung Cancer/Thoracic Malignancies, Patient Reported Outcomes/QoL/Survivorship, Pediatric Cancer

2538 - Safety and Activity of KRAS G12C Inhibitors Combined with Thoracic Radiation Therapy

04:45pm - 06:00pm PT

Hall F

Screen: 16

POSTER

Presenter(s)

Helen Zhang, MD - Memorial Sloan Kettering Cancer Center, New York, NY

H. Y. Zhang¹, D. G. Miller¹, J. Y. Shin¹, B. S. Imber¹, M. Offin², J. Haseltine¹, A. J. Wu¹, C. B. Simone II³, D. Gelblum¹, Y. Yamada¹, P. Iyengar¹, J. Chaft², D. R. Gomez¹, and N. Shaverdian¹; ¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ²Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, ³New York Proton Center, New York, NY

Purpose/Objective(s): The advent of KRAS G12C inhibitors (i.e. sotorasib and adagrasib) has expanded treatment options for patients with advanced NSCLC. However, the impact of combining these inhibitors with thoracic radiation is poorly understood. We aimed to evaluate toxicity and disease outcomes in patients treated with concurrent thoracic radiation therapy (RT) and KRAS G12C inhibitors.

Materials/Methods: Consecutive patients with advanced NSCLC treated with concurrent thoracic RT and either sotorasib or adagrasib between July 2021 - April 2024 were reviewed. Concurrent KRAS inhibitor use was defined as the use of the drug during RT or within 14 days before or after RT. Thoracic RT was defined as RT directed to the lungs, chest wall, or thoracic spine. Treatment-related toxicities including pneumonitis, esophagitis, pain flare, and myositis were graded according to CTCAE v5. Fisher’s exact test was used to compare the rate and severity of toxicities between patients who held and did not hold KRAS G12C inhibitors on RT days. Local failure (LF) was defined as disease progression within the RT fields and was analyzed using the cumulative incidence (CI) function.

Results: In total, 41 patients were included of whom 32 (78%) received sotorasib and 9 (22%) received adagrasib. KRAS inhibitor was continued daily during RT by 23 patients (56%) and held during RT by 18 patients (44%). RT was delivered to the thoracic spine (n=20, 49%), lung (n=15, 37%) and chest wall (n=6, 15%). The most common RT regimens were 30 Gy / 3 fx (22%, n=9), 20 Gy / 5 fx (20%, n=8), and 45 Gy / 15 fx (10%, n=4). Table 1 shows toxicities. There was one grade 3 event (pneumonitis). There were no significant differences in the incidence of toxicities between patients who held versus continued their KRAS inhibitor daily through RT. At a median follow-up of 15 months, there were 5 total local failure events. The estimated 12-month cumulative incidence of local failure was 17.0% (95% CI 0 – 33.4%).

Conclusion: This is one of the first analyses of toxicity and disease outcomes in patients treated with concurrent KRAS G12C inhibitors and RT. The overall rate of toxicities was low, and continued use of KRAS G12C inhibitors daily during RT did not significantly increase toxicities. Furthermore, local control appears favorable in the context of palliative RT doses. Future studies exploring this combination of therapies are warranted.

Abstract 2538 - Table 1: Toxicities of concurrent thoracic RT and KRAS G12C inhibitors

	Overall (n = 41)	Drug Held During RT (n = 18)	Drug Continued During RT (n = 23)	p-value
Pneumonitis				0.3
Grade 2	2 (5%)	0	2 (9)
Grade 3	1 (2%)	1 (6%)	0
Esophagitis				0.3
Grade 1	2 (5%)	2 (11%)	0
Grade 2	6 (15%)	2 (11%)	4 (17%)
Pain Flare				0.6
Grade 2	4 (10%)	1 (6%)	3 (13%)
Myositis				0.2
Grade 1	1 (2%)	1 (6%)	0
Grade 2	1 (2%)	1 (6%)	0