2115 - Comprehensive Assessment of Pneumonitis, Pseudoprogression and Hyperprogression among Inoperable Stage III NSCLC Patients Treated with Trimodal Therapy

J. Paragas^1,2, M. Duclos¹, L. A. Alvarado^1,3, F. Cabrera³, D. Mahmoud^1,4, S. Alshehri^1,5, I. J. Gerard¹, A. Joseph¹, N. Kopek⁶, S. L. Faria¹, E. Zhang¹, B. Shieh¹, S. Owen¹, L. Ofiara¹, and B. S. Abdulkarim⁶; ¹McGill University Health Centre, Montreal, QC, Canada, ²Lung Center of the Philippines, Quezon City, Philippines, ³Hope International Radiotherapy Center, Guatemala, Guatemala, ⁴American University of Beirut Medical Center, Beirut, Lebanon, ⁵Prince Sultan Medical City, Riyadh, Saudi Arabia, ⁶Department of Radiation Oncology, McGill University Health Centre, Montreal, QC, Canada

Purpose/Objective(s): The standard of care for patients with inoperable stage III NSCLC is chemoradiotherapy (CRT) followed by Durvalumab. Since the adoption of the Pacific protocol, the interplay of adverse events between RT and durvalumab has been recognized but is not fully investigated. The purpose of this study is to evaluate the rates of pneumonitis (ClinPneumo), pseudoprogression (PseudoP) and hyperprogression (HyperP) in inoperable stage III NSCLC patients. Materials/

Methods: A retrospective review was conducted within a 4-year period (2018-2022). Patients receiving either concurrent CRT (cCRT) or sequential CRT (sCRT) followed by Durvalumab were included and matched with an equal number not receiving Durvalumab. Two blinded radiation oncologists evaluated CBCT images during RT and two blinded radiologists evaluated diagnostic CT (dCT) during adjuvant Durvalumab for ClinPneumo, PseudoP (RECIST v1.1) and HyperP (Russo et al 2019). Univariate and multivariate analyses were used to assess correlation.
Results: A total of 146 patients were included in the analysis: median age was 69 years, 98% adenocarcinoma or squamous cell carcinoma, 59% with PDL1>1%, and 7% with targetable mutations. After a median follow-up of 17 months, median PFS was 29/21months for the cCRT/sCRT plus Durvalumab as compared to 10/13 months for the cCRT/sCRT without Durvalumab group. Median OS was not reached for cCRT/sCRT + Durvalumab. ClinPneumo Grade >/=2 were 40.4% and 10.6% for patients who received cCRT +/- Durvalumab as compared to 18.8% and 6.3% for the sCRT +/- Durvalumab. Only 9.7% of the patients with ClinPneumo during cCRT/sCRT had a CBCT-correlate, while 68% of patients with ClinPneumo during immunotherapy had a dCT-correlate. A total of 12 patients (7%) exhibited PseudoP while 9 patients (5.5%) demonstrated HyperP. On multivariate analysis, Durvalumab and cCRT (compared to sCRT) were independent prognostic factors increasing the risk of ClinPneumo [cCRT: OR 6.03, P=0.04; Durvalumab OR 13.74, P=0.0007]. However, dosimetric parameters (tumor volume, V5 and V20Gy) were not associated with increased risk of developing ClinPneumo. None of these factors had a significant correlation with PseudoP and HyperP in multivariate analyses.
Conclusion: This is the largest study evaluating ClinPneumo, PseudoP and HyperP in stage III NSCLC patients. We showed that adjuvant Durvalumab improved PFS in both cCRT and sCRT. Durvalumab and cCRT are independent prognostic factors associated with increasing the risk of ClinPneumo. These results were comparable to the Pacific trial. However, additional prospective studies are warranted to further assess the risk on PseudoP and HyperP in unresectable stage III NSCLC.