Predictive ability of a drug-based score in patients with advanced non–small-cell lung cancer receiving first-line immunotherapy
| Autor: | Giampiero Porzio, Luigi Della Gravara, Carlo Genova, Danilo Rocco, Luca Cantini, Sebastiano Buti, Sergio Bracarda, Marco Filetti, Alessandro Tuzi, R. Bisonni, Giulio Metro, Claudia Bareggi, Francesco Grossi, Francesca Mazzoni, Alfredo Addeo, David J. Pinato, Emilio Bria, Giovanni Mansueto, Vincenzo Adamo, Joachim G.J.V. Aerts, Raffaele Giusti, Diego Signorelli, Alessio Cortellini, Miriam Grazia Ferrara, Giorgia Guaitoli, Lorenza Landi, Corrado Ficorella, Gabriele Minuti, Fabiana Perrone, Fabrizio Citarella, Melissa Bersanelli, Giuseppe Luigi Banna, Emanuela Olmetto, Marina Chiara Garassino, Marco Siringo, Alain Gelibter, Michele De Tursi, Marco Russano, Giulia Mazzaschi, Gian Paolo Spinelli, Vincenzo Sforza, Luca Carmisciano, Rita Chiari, Katia Cannita, Fabrizio Tabbò, Diego Cortinovis, Alessandro De Toma, Serena Ricciardi, Stefania Gori, Olga Nigro, Mariangela Torniai, Rossana Berardi, Marcello Tiseo, Maria Rita Migliorino, Fausto Barbieri, Alessandro Follador, Alessandro Russo, Massimo Di Maio, Pietro Di Marino, Alex Friedlaender, Federica Zoratto |
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| Přispěvatelé: | Pulmonary Medicine |
| Rok vydání: | 2021 |
| Předmět: |
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0301 basic medicine Oncology Cancer Research Lung Neoplasms medicine.medical_treatment Pembrolizumab Predictive score 0302 clinical medicine Adrenal Cortex Hormones Risk Factors Carcinoma Non-Small-Cell Lung Monoclonal Drug Interactions Concomitant medications First-line Immunotherapy Non–small-cell lung cancer Non-Small-Cell Lung Aged Anti-Bacterial Agents Antibodies Monoclonal Humanized Clinical Decision-Making Female Humans Immune Checkpoint Inhibitors Italy Patient Selection Polypharmacy Predictive Value of Tests Progression-Free Survival Proton Pump Inhibitors Reproducibility of Results Retrospective Studies Risk Assessment Decision Support Techniques Humanized 030220 oncology & carcinogenesis Cohort Cohort study medicine.medical_specialty Antibodies 03 medical and health sciences SDG 3 - Good Health and Well-being Internal medicine medicine Progression-free survival Lung cancer Chemotherapy business.industry Carcinoma Case-control study medicine.disease 030104 developmental biology Concomitant business |
| Zdroj: | European Journal of Cancer, 150, 224-231. Elsevier Ltd. |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/j.ejca.2021.03.041 |
| Popis: | Background: We previously demonstrated the cumulative poor prognostic role of concomitant medications on the clinical outcome of patients with advanced cancer treated with immune checkpoint inhibitors, creating and validating a drug-based prognostic score to be calculated before immunotherapy initiation in patients with advanced solid tumours. This ‘drug score’ was calculated assigning score 1 for each between proton-pump inhibitor and antibiotic administration until a month before cancer therapy initiation and score 2 in case of corticosteroid intake. The good risk group included patients with score 0, intermediate risk with score 1–2 and poor risk with score 3–4. Methods: Aiming at validating the prognostic and putative predictive ability depending on the anticancer therapy, we performed the present comparative analysis in two cohorts of advanced non–small-cell lung cancer (NSCLC), respectively, receiving first-line pembrolizumab or chemotherapy through a random case-control matching and through a pooled multivariable analysis including the interaction between the computed score and the therapeutic modality (pembrolizumab vs chemotherapy). Results: Nine hundred fifty and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. After the case-control random matching, 589 patients from the pembrolizumab cohort and 589 from the chemotherapy cohort were paired, with no statistically significant differences between the characteristics of the matched subjects. Among the pembrolizumab-treated group, good, intermediate and poor risk evaluable patients achieved an objective response rate (ORR) of 50.0%, 37.7% and 23.4%, respectively, (p < 0.0001), whereas among the chemotherapy-treated group, patients achieved an ORR of 37.0%, 40.0% and 32.4%, respectively (p = 0.4346). The median progression-free survival (PFS) of good, intermediate and poor risk groups was 13.9 months, 6.3 months and 2.8 months, respectively, within the pembrolizumab cohort (p < 0.0001), and 6.2 months, 6.2 months and 4.3 months, respectively, within the chemotherapy cohort (p = 0.0280). Among the pembrolizumab-treated patients, the median overall survival (OS) for good, intermediate and poor risk patients was 31.4 months, 14.5 months and 5.8 months, respectively, (p < 0.0001), whereas among the chemotherapy-treated patients, it was 18.3 months, 16.8 months and 10.6 months, respectively (p = 0.0003). A similar trend was reported considering the two entire populations. At the pooled analysis, the interaction term between the score and the therapeutic modality was statistically significant with respect to ORR (p = 0.0052), PFS (p = 0.0003) and OS (p < 0.0001), confirming the significantly different effect of the score within the two cohorts. Conclusion: Our ‘drug score’ showed a predictive ability with respect to ORR in the immunotherapy cohort only, suggesting it might be a useful tool for identifying patients unlikely to benefit from first-line single-agent pembrolizumab. In addition, the prognostic stratification in terms of PFS and OS was significantly more pronounced among the pembrolizumab-treated patients. |
| Databáze: | OpenAIRE |
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