PGY-2 Oncology Pharmacy Resident University of North Carolina Medical Center Chapel Hill, North Carolina, United States
Poster Abstract:
Background: The standard of care for patients with stage III, unresectable non-small cell lung cancer (NSCLC) is curative intent chemoradiation followed by consolidative durvalumab. However, most patients progress necessitating further treatment. Although immunotherapy (IO) is the cornerstone of treatment in advanced/metastatic disease, the benefit in those who received prior durvalumab is unclear. Clinical trials excluded prior IO exposure and current guidelines do not provide specific recommendations.
Objective: This study aims to characterize the efficacy of post-durvalumab IO treatment.
Methods: This was a retrospective cohort study conducted at the University of North Carolina (UNC) Medical Center. Adult patients with unresectable NSCLC who received chemoradiation and consolidative durvalumab followed by subsequent systemic therapy for disease progression between February 2018 to May 2023 were included. Patients were excluded if they received targeted therapy as subsequent therapy. The primary endpoint was real-world progression-free survival (rwPFS) of post-durvalumab treatment. Key secondary outcomes included physician assessed response, overall survival (OS), and subgroup analyses to identify biomarkers which may predict benefit from IO retreatment.
Results: A total of 66 patients met inclusion criteria, of which 39 (59%) received subsequent chemotherapy alone and 27 (41%) received IO-containing therapy. Of those who received IO-containing treatments, 18 received chemotherapy plus IO (chemoIO) and 9 received IO alone. Durvalumab was discontinued for therapy completion (chemotherapy: 18%, IO: 26%), disease progression (chemotherapy: 54%, IO: 48%), or side effects (chemotherapy: 26%, IO: 19%). No significant difference was observed between median rwPFS of chemotherapy versus IO-containing therapy (7.0 months vs 5.8 months, respectively; p = 0.9419) or OS (13.0 months vs 12.6 months, respectively; p = 0.5769). Notably, patients in our cohort who received IO alone had a numerically longer rwPFS compared to chemoIO (12.6 months vs 5.8 months, respectively; p = 0.3951) and a numerically longer OS (12.6 months vs 6.4 months, respectively; p = 0.8885). Discussion/
Conclusions: This study found that there were no statistically significant differences in median rwPFS or OS between chemotherapy or IO-based regimens following the conclusion of durvalumab consolidation. Interestingly, we observed a numerically improved rwPFS and OS in those who received IO alone compared to chemoIO, which suggests there may be key clinical or molecular features that may help identify patients who benefit from IO therapy. We acknowledge the limitations of this small, retrospective study. The efficacy of IO-based regimens post-durvalumab warrants further investigation in a larger, prospective manner to assess the risks and benefits of IO retreatment.
References (must also be included in final poster): 1. Aupérin A, Le Péchoux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, Yamanaka T, Bozonnat MC, Uitterhoeve A, Wang X, Stewart L, Arriagada R, Burdett S, Pignon JP. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010 May 1;28(13):2181-90. doi: 10.1200/JCO.2009.26.2543. Epub 2010 Mar 29. PMID: 20351327. 2. Yoon SM, Shaikh T, Hallman M. Therapeutic management options for stage III non-small cell lung cancer. World J Clin Oncol. 2017 Feb 10;8(1):1-20. doi: 10.5306/wjco.v8.i1.1. PMID: 28246582; PMCID: PMC5309711. 3. Ahn JS, Ahn YC, Kim JH, et al. Multinational randomized phase III trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small-cell lung cancer: KCSG-LU05-04. J Clin Oncol 2015;33:2660-2666 4. Imfinzi. Package Insert. AstraZeneca; 2020. 5. Agustoni F, Hirsch FR. PACIFIC trial: new perspectives for immunotherapy in lung cancer. Transl Lung Cancer Res. 2018 Feb;7(Suppl 1):S19-S24. doi: 10.21037/tlcr.2017.12.12. PMID: 29531898; PMCID: PMC5835637. 6. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeño J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Özgüroğlu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8. PMID: 28885881. 7. Ge X, Zhang Z, Zhang S, Yuan F, Zhang F, Yan X, Han X, Ma J, Wang L, Tao H, Li X, Zhi X, Huang Z, Hofman P, Prelaj A, Banna GL, Mutti L, Hu Y, Wang J. Immunotherapy beyond progression in patients with advanced non-small cell lung cancer. Transl Lung Cancer Res. 2020 Dec;9(6):2391-2400. doi: 10.21037/tlcr-20-1252. PMID: 33489801; PMCID: PMC7815351. 8. Sheth S, Gao C, Mueller N, Angra N, Gupta A, Germa C, Martinez P, Soria JC. Durvalumab activity in previously treated patients who stopped durvalumab without disease progression. J Immunother Cancer. 2020 Aug;8(2):e000650. doi: 10.1136/jitc-2020-000650. PMID: 32847985; PMCID: PMC7451272. 9. Cai Z, Zhan P, Song Y, Liu H, Lv T. Safety and efficacy of retreatment with immune checkpoint inhibitors in non-small cell lung cancer: a systematic review and meta-analysis. Transl Lung Cancer Res. 2022 Aug;11(8):1555-1566. doi: 10.21037/tlcr-22-140. PMID: 36090645; PMCID: PMC9459604.