Lead Investigator: Marco Tagliamento, IRCCS Ospedale Policlinico San Martino
Title of Proposal Research: Clinical Effect of Chemotherapy-Immunotherapy Combination in the First-Line Treatment of Older Patients with Non-Small Cell Lung Cancer
Vivli Data Request: 7840
Funding Source: None
Potential Conflicts of Interest: Dr. Tagliamento reports: travel grants from Roche, Bristol-Myers Squibb, AstraZeneca, Takeda, Eli Lilly and Honoraria as medical writer from Novartis, Amgen, MSD. Some of these disclosures refer to more that 2 years ago, and all of them have no connection with the submitted research project.
Benjamin Besse reports: Sponsored Research at Gustave Roussy Cancer Center: Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. None related to the current project.
Matteo Lambertini acted as adviser for Roche, AstraZeneca, Eli Lilly, and Novartis; and received honoraria from Takeda, Roche, AstraZeneca, Eli Lilly, Pfizer, Novartis, and Sandoz. None of these conflicts of interest is related to the current project.
Summary of the Proposed Research:
Lung cancer is one of the most frequently occurring cancer worldwide and is responsible for the greatest burden in terms of cancer-related deaths. Based on the Surveillance, Epidemiology, and End Results (SEER) database, it has been estimated that 47% of lung cancer diagnoses performed before 2003 in the U.S. occurred in patients aged 70 or above, with 14% of the cases diagnosed in patients aged 80 years and older (i.e., “oldest old” patients). In the context of a remarkable aging of the population worldwide, the fastest-growing proportion is represented by people older than 65 years. The treatment of lung cancer among older patients may be challenging due to several reasons. While by itself advanced age does not represent an exclusion criterion in most clinical trials, the increased vulnerability of older patients participates to explain their underrepresentation in clinical trials. Such poor representation of older patients in randomized clinical trial makes so that truly evidence-based decisions on the best type of treatment for geriatric patients can sometimes difficultly be made. Cancer trials with drugs blocking immune checkpoints (i.e., immune checkpoint blockers, ICBs) are no exception to this phenomenon. Immune checkpoints are regulators of the immune system and are crucial to controlling immune responses. The median age of patients with lung cancer treated in pivotal trials involving immunotherapy ranged between 61 and 65 years, which is lower than the median age at diagnosis. While immunotherapy alone has a better toxicity profile than chemotherapy, combination regimens may have more significant adverse events and are currently proposed to patients with lung cancer aged 70 years or older only if fit, and on a case-by-case evaluation. We therefore aim to define if the standard upfront systemic therapy for patients with non-small cell lung cancer (NSCLC) could be considered effective and safe in older patients. We will therefore aim to provide evidence about efficacy and safety of the standard upfront treatment for the metastatic disease, that is a combination of chemotherapy with platinum and agents that inhibit checkpoints of the immune system like the programmed death protein 1 (PD-1) and its ligand PD-L1, in older patients with lung cancer.
Our objective is to use the results of the clinical trials to compare clinical effects of upfront chemotherapy with platinum combined or not with the immunotherapeutic drug atezolizumab (i.e., data from IMpower studies) in patients with NSCLC older than 70 years vs. under the age of 70. More precisely, we will compare outcomes of survival and disease response to treatment, as well as data about adverse events (AEs) and treatment discontinuation rates between these two subgroups of patients.
This research project can generate results that may improve the curative treatment of older patients with advances stage NSCLC, by reducing the attitude to undertreat them.
Requested Studies:
A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel With or Without Bevacizumab Compared With Carboplatin + Paclitaxel + Bevacizumab in Chemotherapy-Naïve Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02366143
Sponsor ID: GO29436
A Phase III Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Nab-Paclitaxel for Chemotherapy-Naive Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02367781
Sponsor ID: GO29537
A Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel or Atezolizumab in Combination With Carboplatin+Nab-Paclitaxel Versus Carboplatin+Nab-Paclitaxel in Chemotherapy-Naive Patients With Stage IV Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02367794
Sponsor ID: GO29437
A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-Pd-L1 Antibody) in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Patients Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02657434
Sponsor ID: GO29438