Plunging Into the PACIFIC: Outcomes of Patients With Unresectable KRAS-Mutated Non-Small Cell Lung Cancer Following Definitive Chemoradiation and Durvalumab Consolidation

Adam Barsouk; Cole Friedes; Michelle Iocolano; Abigail Doucette; Roger B Cohen; Kyle W Robinson; Christopher A D'Avella; Melina E Marmarelis; John A Kosteva; Aditi P Singh; Christine A Ciunci; William P Levin; Keith A Cengel; Jeffrey D Bradley; Steven J Feigenberg; Lova Sun; Charu Aggarwal; Corey J Langer; Nikhil Yegya-Raman

doi:10.1016/j.cllc.2023.12.009

Plunging Into the PACIFIC: Outcomes of Patients With Unresectable KRAS-Mutated Non-Small Cell Lung Cancer Following Definitive Chemoradiation and Durvalumab Consolidation

Clin Lung Cancer. 2023 Dec 22:S1525-7304(23)00266-8. doi: 10.1016/j.cllc.2023.12.009. Online ahead of print.

Authors

Adam Barsouk¹, Cole Friedes², Michelle Iocolano², Abigail Doucette², Roger B Cohen³, Kyle W Robinson³, Christopher A D'Avella³, Melina E Marmarelis³, John A Kosteva³, Aditi P Singh³, Christine A Ciunci³, William P Levin², Keith A Cengel², Jeffrey D Bradley², Steven J Feigenberg², Lova Sun³, Charu Aggarwal³, Corey J Langer³, Nikhil Yegya-Raman⁴

Affiliations

¹ Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address: Adam.barsouk@pennmedicine.upenn.edu.
² Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
³ Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
⁴ Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address: Nikhil.Yegya-Raman@pennmedicine.upenn.edu.

PMID: 38195320
DOI: 10.1016/j.cllc.2023.12.009

Abstract

Background: Immune checkpoint inhibitor (ICI) consolidation following concurrent chemoradiotherapy (CRT) substantially improved progression free survival (PFS) and overall survival (OS) in the PACIFIC trial becoming the standard of care in locally-advanced, unresectable NSCLC. KRAS mutation may influence response to ICI.

Methods: In this single-institution, retrospective analysis, we compared treatment outcomes for patients with unresectable KRAS mutated (KRAS-mt) and wild-type (KRAS-wt) NSCLC treated with CRT between October 2017 and December 2021. Kaplan-Meier analysis was conducted comparing median progression free survival and median overall survival from completion of radiotherapy in all KRAS-mt patients and KRAS-G12C-mutated patients. Outcomes were also compared with and without ICI consolidation.

Results: Of 156 patients, 42 (26.9%) were KRAS-mt and 114 (73.1%) were KRAS-wt. Baseline characteristics differed only in histology; KRAS-mt NSCLC more likely to be adenocarcinoma. KRAS-mt patients had worse PFS (median 6.3 vs. 10.7 months, P = .041) but similar OS (median 23.1 vs. 27.3 months, P = .237). KRAS-mt patients were more likely to not receive ICI due to rapid disease progression post-CRT (23.8% vs. 4.4%, P = .007). Among patients who received ICI (n = 114), KRAS-mt was not associated with inferior PFS (8.1 vs. 11.9 months, P = .355) or OS (30.5 vs. 31.7 months, P = .692). KRAS-G12C patients (n = 22) had similar PFS and OS to other KRAS-mt.

Conclusion: In one of the largest post-CRT KRAS-mt cohort published, KRAS-mt was associated with inferior PFS, largely due to rapid progression prior to ICI consolidation, but did not affect OS. Among those who received ICI consolidation, outcomes were comparable regardless of KRAS-mt status.

Keywords: immunotherapy; locally advanced NSCLC.