Ithar Gataa1, Laura Mezquita2, Caroline Rossoni3, Edouard Auclin4, Myriam Kossai5, Frank Aboubakar6, Sylvestre Le Moulec7, Julie Massé8, Morgane Masson9, Nina Radosevic-Robin10, Pierre Alemany11, Mathieu Rouanne12, Virginia Bluthgen13, Lizza Hendriks14, Caroline Caramella15, Anas Gazzah16, David Planchard17, Jean-Pierre Pignon18, Benjamin Besse19, Julien Adam20. 1. Cancer Medicine Department, Gustave Roussy, Villejuif, France; Medical Oncology Department, Cochin Hospital, Paris, France. Electronic address: Ithar.gataa@aphp.fr. 2. Cancer Medicine Department, Gustave Roussy, Villejuif, France; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Barcelona, Spain. Electronic address: lmezquita@clinic.cat. 3. Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, Villejuif, France; Inserm, University Paris-Saclay, Labeled Ligue Contre le Cancer, Oncostat, U1018, Villejuif, France. Electronic address: caroline.rossoni@outlook.fr. 4. Medical and Thoracic Oncology Department, Hôpital Européen Georges Pompidou AP-HP, Paris, France. Electronic address: ed.auclin@gmail.com. 5. Pathology Department, Gustave Roussy, Villejuif, France. Electronic address: myriamkossai@gmail.com. 6. Cancer Medicine Department, Gustave Roussy, Villejuif, France. Electronic address: frank.aboubakar@uclouvain.be. 7. Medical Oncology Department, Institut Bergonié, Bordeaux, France. Electronic address: sylvestre.lemoulec@gmail.com. 8. Pathology Department, Institut Bergonié, Bordeaux, France. Electronic address: julie.masse@cjp.fr. 9. Medical Oncology Department, Centre Jean Perrin, Clermont-Ferrand, France. Electronic address: morganemasson1@hotmail.fr. 10. Pathology Department, Centre Jean Perrin, Clermont-Ferrand, France. Electronic address: nina.radosevic.robin@gmail.com. 11. Pathology Department, Gustave Roussy, Villejuif, France. Electronic address: pierre.alemany@yahoo.fr. 12. INSERM U1015, Gustave Roussy, Villejuif, France; Hôpital Foch, UVSQ-Université Paris-Saclay, Suresnes, France. Electronic address: mathieu.rouanne@gustaveroussy.fr. 13. Cancer Medicine Department, Gustave Roussy, Villejuif, France. Electronic address: mvbluthgen@gmail.com. 14. Cancer Medicine Department, Gustave Roussy, Villejuif, France; Department of Pulmonary Diseases, GROW - School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, the Netherlands. Electronic address: lizza.hendriks@mumc.nl. 15. Radiology Department, Gustave Roussy, Villejuif, France. Electronic address: Caroline.caramella@gmail.com. 16. Early Drug Development Department, Gustave Roussy, Villejuif, France. Electronic address: anas.gazzah@gustaveroussy.fr. 17. Cancer Medicine Department, Gustave Roussy, Villejuif, France. Electronic address: david.planchard@gustaveroussy.fr. 18. Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, Villejuif, France; Inserm, University Paris-Saclay, Labeled Ligue Contre le Cancer, Oncostat, U1018, Villejuif, France. Electronic address: Jean-pierre.PIGNON@gustaveroussy.fr. 19. Cancer Medicine Department, Gustave Roussy, Villejuif, France; Paris-Saclay University, Faculty of Medicine, Le Kremlin, Bicêtre, France. Electronic address: benjamin.besse@gustaveroussy.fr. 20. Pathology Department, Gustave Roussy, Villejuif, France. Electronic address: julien.adam@gustaveroussy.fr.
Abstract
BACKGROUND: The established role of morphological evaluation of tumour-infiltrating lymphocytes (TILs) with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) is unknown. We aimed to determine TIL association with the outcome for ICIs and for chemotherapy in advanced NSCLC. METHODS: This is a multicenter retrospective study of a nivolumab cohort of 221 patients treated between November 2012 and February 2017 and a chemotherapy cohort of 189 patients treated between June 2009 and October 2016. Patients with available tissue for stromal TIL evaluation were analysed. The presence of a high TIL count (high-TIL) was defined as ≥10% density. The primary end-point was overall survival (OS). RESULTS: Among the nivolumab cohort, 64% were male, with median age of 63 years, 82.3% were smokers, 77% had performance status ≤1 and 63% had adenocarcinoma histology. High-TIL was observed in 22% patients and associated with OS (hazard ratio [HR] 0.48; 95% confidence interval [95% CI]: 0.28-0.81) and progression-free survival [PFS] (HR = 0.40; 95% CI: 0.25-0.64). Median PFS was 13.0 months (95% CI: 5.0-not reached) with high-TIL versus 2.2 months (95% CI: 1.7-3.0) with the presence of a low TIL count (low-TIL). Median OS for high-TIL was not reached (95% CI: 12.2-not reached) versus 8.4 months (95% CI: 5.0-11.6) in the low-TIL group. High-TIL was associated with the overall response rate (ORR) and disease control rate (DCR) (both, P < .0001). Among the chemotherapy cohort, 69% were male, 89% were smokers, 86% had performance status ≤1 and 90% had adenocarcinoma histology. High-TIL was seen in 37%. Median PFS and OS were 5.7 months (95% CI: 4.9-6.7) and 11.7 months (95% CI: 9.3-13.0), respectively, with no association with TILs. CONCLUSIONS: High-TIL was associated with favourable outcomes in a real-world immunotherapy cohort of patients with NSCLC, but not with chemotherapy, suggesting that TILs may be useful in selecting patients for immunotherapy.
BACKGROUND: The established role of morphological evaluation of tumour-infiltrating lymphocytes (TILs) with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) is unknown. We aimed to determine TIL association with the outcome for ICIs and for chemotherapy in advanced NSCLC. METHODS: This is a multicenter retrospective study of a nivolumab cohort of 221 patients treated between November 2012 and February 2017 and a chemotherapy cohort of 189 patients treated between June 2009 and October 2016. Patients with available tissue for stromal TIL evaluation were analysed. The presence of a high TIL count (high-TIL) was defined as ≥10% density. The primary end-point was overall survival (OS). RESULTS: Among the nivolumab cohort, 64% were male, with median age of 63 years, 82.3% were smokers, 77% had performance status ≤1 and 63% had adenocarcinoma histology. High-TIL was observed in 22% patients and associated with OS (hazard ratio [HR] 0.48; 95% confidence interval [95% CI]: 0.28-0.81) and progression-free survival [PFS] (HR = 0.40; 95% CI: 0.25-0.64). Median PFS was 13.0 months (95% CI: 5.0-not reached) with high-TIL versus 2.2 months (95% CI: 1.7-3.0) with the presence of a low TIL count (low-TIL). Median OS for high-TIL was not reached (95% CI: 12.2-not reached) versus 8.4 months (95% CI: 5.0-11.6) in the low-TIL group. High-TIL was associated with the overall response rate (ORR) and disease control rate (DCR) (both, P < .0001). Among the chemotherapy cohort, 69% were male, 89% were smokers, 86% had performance status ≤1 and 90% had adenocarcinoma histology. High-TIL was seen in 37%. Median PFS and OS were 5.7 months (95% CI: 4.9-6.7) and 11.7 months (95% CI: 9.3-13.0), respectively, with no association with TILs. CONCLUSIONS: High-TIL was associated with favourable outcomes in a real-world immunotherapy cohort of patients with NSCLC, but not with chemotherapy, suggesting that TILs may be useful in selecting patients for immunotherapy.
Authors: Richard J Straker; Katharine Krupp; Cimarron E Sharon; Alexandra S Thaler; Nicholas J Kelly; Emily Y Chu; David E Elder; Xiaowei Xu; John T Miura; Giorgos C Karakousis Journal: Ann Surg Oncol Date: 2022-03-17 Impact factor: 4.339