Ana Ortega-Franco1, Clare Hodgson2, Haseem Raja3, Mathew Carter4, Colin Lindsay4,5, Sarah Hughes4, Laura Cove-Smith4,5, Paul Taylor4, Yvonne Summers4,5, Fiona Blackhall4,5, Raffaele Califano6,7. 1. Experimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester, UK. 2. Digital Services, The Christie NHS Foundation Trust, Manchester, UK. 3. Department of ENT, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 4. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK. 5. Division of Cancer Sciences, University of Manchester, Manchester, UK. 6. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK. raffaele.califano@nhs.net. 7. Division of Cancer Sciences, University of Manchester, Manchester, UK. raffaele.califano@nhs.net.
Abstract
BACKGROUND: Pembrolizumab is licensed for the treatment of pre-treated and PD-L1 positive non-small cell lung cancer (NSCLC), but response is heterogeneous. In this context, the Lung Immune Prognostic Index (LIPI) has been proposed as tool to prognosticate outcome. OBJECTIVE: To investigate the real-world efficacy and safety of pembrolizumab in pre-treated NSCLC patients and the clinical utility of LIPI for patients' selection. PATIENTS AND METHODS: Patients with pre-treated NSCLC and PD-L1 ≥ 1% treated with pembrolizumab were included in this retrospective series. The LIPI was used to classify patients in 3 prognostics subgroups according to the pre-treatment dNLR (derived neutrophil to lymphocyte ratio) and LDH in blood. The prognostic impact of the LIPI on progression free survival (PFS) and overall survival (OS) was evaluated with Cox regression. The combined effect of LIPI and other relevant prognostic factors was explored with multivariate regression. RESULTS: In total, 113 consecutive patients were included. Median (mPFS) and mOS was 4.3 (2.6-6.7) and 13.5 (10.3-17.7) months, respectively. Good-, intermediate-, and poor-LIPI was found in 54 (47.8%), 45 (39.8%), and 8 (7.1%) patients, respectively. Median PFS was 5.1 (2.8-9.1), 3.0 (2.5-6.8), and 1.4 (0.5-18.7) months, and mOS was 17.2 (12.0-26.4), 11.8 (8.4-17.1), and 3.7 (0.5-not calculable) months for good-, intermediate-, and poor-LIPI group, respectively. Patients with intermediate-LIPI and poor-LIPI had worse PFS versus good-LIPI, and statistically significant worse OS (p = 0.030 and p = 0.013, respectively). In the multivariate analysis, intermediate- versus good-LIPI (p = 0.190) was not independently associated to PFS or OS. Patients with both good-LIPI and high (≥ 50%) PD-L1 had better OS than all other subgroups defined by LIPI and PD-L1. Immune-related adverse events (irAEs) occurred in 47 (41.6%) patients (12.4% grade ≥ 3). In a time-varying analysis, irAEs were statistically associated with longer OS (HR 0.51, 0.31-0.84; p = 0.008). CONCLUSION: In our series, the outcome of pembrolizumab in pre-treated NSCLC is consistent with the registration trial. Lung Immune Prognostic Index is a readily available tool able to prognosticate outcome, also in PD-L1-high patients. The positive association between irAEs and OS might aid decision making.
BACKGROUND: Pembrolizumab is licensed for the treatment of pre-treated and PD-L1 positive non-small cell lung cancer (NSCLC), but response is heterogeneous. In this context, the Lung Immune Prognostic Index (LIPI) has been proposed as tool to prognosticate outcome. OBJECTIVE: To investigate the real-world efficacy and safety of pembrolizumab in pre-treated NSCLC patients and the clinical utility of LIPI for patients' selection. PATIENTS AND METHODS: Patients with pre-treated NSCLC and PD-L1 ≥ 1% treated with pembrolizumab were included in this retrospective series. The LIPI was used to classify patients in 3 prognostics subgroups according to the pre-treatment dNLR (derived neutrophil to lymphocyte ratio) and LDH in blood. The prognostic impact of the LIPI on progression free survival (PFS) and overall survival (OS) was evaluated with Cox regression. The combined effect of LIPI and other relevant prognostic factors was explored with multivariate regression. RESULTS: In total, 113 consecutive patients were included. Median (mPFS) and mOS was 4.3 (2.6-6.7) and 13.5 (10.3-17.7) months, respectively. Good-, intermediate-, and poor-LIPI was found in 54 (47.8%), 45 (39.8%), and 8 (7.1%) patients, respectively. Median PFS was 5.1 (2.8-9.1), 3.0 (2.5-6.8), and 1.4 (0.5-18.7) months, and mOS was 17.2 (12.0-26.4), 11.8 (8.4-17.1), and 3.7 (0.5-not calculable) months for good-, intermediate-, and poor-LIPI group, respectively. Patients with intermediate-LIPI and poor-LIPI had worse PFS versus good-LIPI, and statistically significant worse OS (p = 0.030 and p = 0.013, respectively). In the multivariate analysis, intermediate- versus good-LIPI (p = 0.190) was not independently associated to PFS or OS. Patients with both good-LIPI and high (≥ 50%) PD-L1 had better OS than all other subgroups defined by LIPI and PD-L1. Immune-related adverse events (irAEs) occurred in 47 (41.6%) patients (12.4% grade ≥ 3). In a time-varying analysis, irAEs were statistically associated with longer OS (HR 0.51, 0.31-0.84; p = 0.008). CONCLUSION: In our series, the outcome of pembrolizumab in pre-treated NSCLC is consistent with the registration trial. Lung Immune Prognostic Index is a readily available tool able to prognosticate outcome, also in PD-L1-high patients. The positive association between irAEs and OS might aid decision making.
Authors: D Planchard; S Popat; K Kerr; S Novello; E F Smit; C Faivre-Finn; T S Mok; M Reck; P E Van Schil; M D Hellmann; S Peters Journal: Ann Oncol Date: 2018-10-01 Impact factor: 32.976
Authors: Achim Rittmeyer; Fabrice Barlesi; Daniel Waterkamp; Keunchil Park; Fortunato Ciardiello; Joachim von Pawel; Shirish M Gadgeel; Toyoaki Hida; Dariusz M Kowalski; Manuel Cobo Dols; Diego L Cortinovis; Joseph Leach; Jonathan Polikoff; Carlos Barrios; Fairooz Kabbinavar; Osvaldo Arén Frontera; Filippo De Marinis; Hande Turna; Jong-Seok Lee; Marcus Ballinger; Marcin Kowanetz; Pei He; Daniel S Chen; Alan Sandler; David R Gandara Journal: Lancet Date: 2016-12-13 Impact factor: 79.321
Authors: Julie Brahmer; Karen L Reckamp; Paul Baas; Lucio Crinò; Wilfried E E Eberhardt; Elena Poddubskaya; Scott Antonia; Adam Pluzanski; Everett E Vokes; Esther Holgado; David Waterhouse; Neal Ready; Justin Gainor; Osvaldo Arén Frontera; Libor Havel; Martin Steins; Marina C Garassino; Joachim G Aerts; Manuel Domine; Luis Paz-Ares; Martin Reck; Christine Baudelet; Christopher T Harbison; Brian Lestini; David R Spigel Journal: N Engl J Med Date: 2015-05-31 Impact factor: 91.245
Authors: F A Shepherd; J Dancey; R Ramlau; K Mattson; R Gralla; M O'Rourke; N Levitan; L Gressot; M Vincent; R Burkes; S Coughlin; Y Kim; J Berille Journal: J Clin Oncol Date: 2000-05 Impact factor: 44.544
Authors: Martin Reck; Delvys Rodríguez-Abreu; Andrew G Robinson; Rina Hui; Tibor Csőszi; Andrea Fülöp; Maya Gottfried; Nir Peled; Ali Tafreshi; Sinead Cuffe; Mary O'Brien; Suman Rao; Katsuyuki Hotta; Melanie A Leiby; Gregory M Lubiniecki; Yue Shentu; Reshma Rangwala; Julie R Brahmer Journal: N Engl J Med Date: 2016-10-08 Impact factor: 91.245
Authors: Edward B Garon; Tudor-Eliade Ciuleanu; Oscar Arrieta; Kumar Prabhash; Konstantinos N Syrigos; Tuncay Goksel; Keunchil Park; Vera Gorbunova; Ruben Dario Kowalyszyn; Joanna Pikiel; Grzegorz Czyzewicz; Sergey V Orlov; Conrad R Lewanski; Michael Thomas; Paolo Bidoli; Shaker Dakhil; Steven Gans; Joo-Hang Kim; Alexandru Grigorescu; Nina Karaseva; Martin Reck; Federico Cappuzzo; Ekaterine Alexandris; Andreas Sashegyi; Sergey Yurasov; Maurice Pérol Journal: Lancet Date: 2014-06-02 Impact factor: 79.321
Authors: Nasser Hanna; Frances A Shepherd; Frank V Fossella; Jose R Pereira; Filippo De Marinis; Joachim von Pawel; Ulrich Gatzemeier; Thomas Chang Yao Tsao; Miklos Pless; Thomas Muller; Hong-Liang Lim; Christopher Desch; Klara Szondy; Radj Gervais; Christian Manegold; Sofia Paul; Paolo Paoletti; Lawrence Einhorn; Paul A Bunn Journal: J Clin Oncol Date: 2004-05-01 Impact factor: 44.544
Authors: Hossein Borghaei; Luis Paz-Ares; Leora Horn; David R Spigel; Martin Steins; Neal E Ready; Laura Q Chow; Everett E Vokes; Enriqueta Felip; Esther Holgado; Fabrice Barlesi; Martin Kohlhäufl; Oscar Arrieta; Marco Angelo Burgio; Jérôme Fayette; Hervé Lena; Elena Poddubskaya; David E Gerber; Scott N Gettinger; Charles M Rudin; Naiyer Rizvi; Lucio Crinò; George R Blumenschein; Scott J Antonia; Cécile Dorange; Christopher T Harbison; Friedrich Graf Finckenstein; Julie R Brahmer Journal: N Engl J Med Date: 2015-09-27 Impact factor: 91.245