RenovoRx : Toxicity and Efficacy of Stereotactic Body Radiation Therapy vs. Intensity-Modulated Radiation Therapy for the Treatment of Locally Advanced Pancreatic Cancer in a Phase 3 Trial Presented at the 2023 ASCO Gastrointestinal (ASCO GI) Cancers Symposium

Toxicity and efficacy of stereotactic body radiation therapy vs. intensity-modulated radiation therapy for the treatment of locally advanced pancreatic cancer in a phase 3 trial

Karyn A. Goodman1, Michael J. Pishvaian2,8, Charles D. Lopez3, Kenneth Meredith4, Emmanuel E. Zervos5, Hassan Hatoum6, Ki Y. Chung7, Alex Tsobanoudis8, Daniel J. Berg9, Antonio Ucar10, Reza Nazemzadeh11, Thor Johnson12, Nainesh Parikh13, Brian Kouri14, Christopher Laing15, Brian A. Boone16, Imtiaz Qureshi8, Ramtin Agah8, Amer H. Zureikat17

1Icahn School of Medicine at Mount Sinai , New York, NY; 2Johns Hopkins University, Washington, DC; 3Oregon Health & Science University, Portland, OR; 4Sarasota Memorial Health Care System, Sarasota, FL; 5East Carolina University, Greenville, NC; 6University of Oklahoma, Oklahoma City, OK; 7Prisma Health Cancer Institute, Boiling Springs, SC; 8RenovoRx, Los Altos, CA; 9University of Iowa, Iowa City, IA; 10Miami Cancer Institute, Miami, FL; 11Levine Cancer Institute, Charlotte, NC; 12Medical University of South Carolina, Charleston, SC; 13Moffit Cancer Center, Tampa, FL; 14Wake Forest Baptist Medical Center, Winston-Salem, NC; 15Sutter Cancer Center, Sacramento, CA; 16West Virginia University, Morgantown, WV; 17University of Pittsburgh Medical Center, Pittsburgh, PA

BACKGROUND

Locally advanced pancreatic cancer (LAPC) is one of the deadliest cancers. Radiotherapy (RT) is part of standard management1, but the optimal RT technique has not been determined. The most common approaches are:

• Stereotactic body radiation therapy (SBRT) or
• Chemoradiation using Intensity-modulated radiation therapy (IMRT)

TIGeR-PaCi is a phase III clinical trial investigating the efficacy of intra-arterial chemotherapy treatment utilizing a novel dual-balloon catheter compared to the standard of care. Prior to randomization, patients undergo radiation therapy during the induction phase. Herein, we use clinical data to compare toxicity and efficacy between SBRT and IMRT.

METHODS

LAPC patients with a 0-1 ECOG and diagnosis within 6 weeks begin induction with chemo (IV gemcitabine/nab-paclitaxel) and radiation therapy (SBRT or IMRT) per the study schema:

INDUCTIONRANDOMIZED

IV Gemcitabine +						IV Gemcitabine
Nab-paclitaxel					control	+ Nab-paclitaxel
2 months						4 months
Radiation						1:1	Continuation Therapy
RANDOMIZE
SBRT	until progression
						Intra-arterial
IV Gemcitabine +					test	Gemcitabine
Nab-paclitaxel						8 bi-weekly tx
1 month						4 months

We analyzed data from 134 patients:

• 75 IMRT patients (50 Gy in 25 fractions; concurrent PO capecitabine BID Mon-Fri) or
• 59 SBRT patients (33 Gy in 5 fractions)

The decision for SBRT vs. IMRT was site-driven and not pre-specified by TIGeR-PaC protocol Analyzed:

• Adverse event (AE) Incidenceii during, and 2 weeks post radiation

•	Tumor size	Mean percent changeiii
•	CA 19-9	Mean percent changeiii

CONCLUSION

While this study was not designed as a head-to-head comparison of SBRT versus IMRT, these data suggest that SBRT is better tolerated than IMRT without any compromise in efficacy in patients with LAPC.

• With SBRT, there was less investigator-led withdrawal of patients due to SAE than
  IMRT
• No statistically significant difference in local tumor response between SBRT and IMRT

1National Comprehensive Cancer Network. Pancreatic Adenocarcinoma (Version 2.2022). https://www.nccn.org/professionals/physician_gls/pdf/pa ncreatic.pdf. Accessed December 13, 2022.

RESULTS

The 134 patients across 22 sites (63 male; 68.5 yr median age) showed no significant difference in baseline demographics between patients treated with SBRT or IMRT.

However, AEs were significantly different between the two:

AE

Category		IMRT (N=75)		SBRT (N=59)		p-valueii
Any AE	49	(65.3)	26	(44.1)	*0.015
Gastrointestinal AE	33	(44.0)	10	(16.9)	**0.001
Grade ≥3 AE	20	(26.7)	6	(10.2)	*0.026
Serious AE	10	(13.3)	2	(3.4)	0.066
On-Study Death	1	(1.3)	0	(0.0)	1.000
Withdrawal	9	(12.0)	1	(1.7)	*0.042

iiCalculated using Fisher's exact test; *p-value ≤ 0.05; **p-value ≤ 0.01

Additionally, there was no significant difference between mean CA 19-9 change and mean tumor size change and at baseline between patients treated with SBRT or IMRT.

CA 19-9

Measurement		IMRT (N=17)		SBRT (N=14)		p-valueiii
Mean CA 19-9 Change (%)	-40.7±40	+9.8 ±111	0.262

TUMOR SIZE	IMRT (N=54)		SBRT (N=50)		p-valueiii
	Measurement
	Mean Baseline Long Axis (cm)	4.30	4.04	0.336
	Mean Tumor Size Change (%)	-11.7	-12.6	0.792
	iiiCalculated using independent samples t-test

FUTURE

Further prospective studies addressing this question are needed to determine the optimal RT modality for patients with LAPC. SBRT appears to be the best RT backbone for adding novel therapies such as intra-arterial chemotherapy.

Of the 134 patients, 104 had interpretable imaging data to analyze tumor size and only 31 with
analyzable CA 19-9 data.	iClinicalTrials.gov