First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study

Author(s): Prof Siow Ming Lee, FRCP1;Prof Christian Schulz, MD2;Kumar Prabhash, MD3; Prof Dariusz Kowalski, MD, PhD4;Aleksandra Szczesna, MD, PhD5;Prof Baohui Han, MD6;Achim Rittmeyer, MD7;Toby Talbot, MBBS8;David Vicente, MD9;Prof Raffaele Califano, MD10;Diego Cortinovis, MD11;Anh Tuan Le, MD, PhD12;Dingzhi Huang, MD13;Prof Geoffrey Liu, MD14;Federico Cappuzzo, MD15;Jessica Reyes Contreras, MD16;Prof Martin Reck, MD, PhD17;Ramon Palmero, MD18;Milena Perez Mak, PhD19;Youyou Hu, MSc20;Stefanie Morris, PhD20;Elen Höglander, PhD20;Mary Connors, BSN21;Alice M Biggane, PhD20,22;Hans Kristian Vollan, MD, PhD20;Prof Solange Peters, MD PhD23;
Source: DOI:https://doi.org/10.1016/S0140-6736(23)00774-2
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Patients with poor performance status do better on atezolizumab monotherapy vs. single agent chemotherapy.

BACKGROUND

Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy.

METHODS

This trial was a phase 3, open-label, randomised controlled study conducted at 91 sites in 23 countries across Asia, Europe, North America, and South America. Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0–1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy. Patients were randomised 2:1 by permuted-block randomisation (block size of six) to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or gemcitabine [intravenous]; dosing per local label) at 3-weekly or 4-weekly cycles. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety analyses were conducted in the safety-evaluable population, which included all randomised patients who received any amount of atezolizumab or chemotherapy. This trial is registered with ClinicalTrials.gov, NCT03191786.

FINDINGS

Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). Atezolizumab improved overall survival compared with chemotherapy (median overall survival 10·3 months [95% CI 9·4–11·9] vs 9·2 months [5·9–11·2]; stratified hazard ratio 0·78 [0·63–0·97], p=0·028), with a 2-year survival rate of 24% (95% CI 19·3–29·4) with atezolizumab compared with 12% (6·7–18·0) with chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilisation or improvement of patient-reported health-related quality-of-life functioning scales and symptoms and fewer grade 3–4 treatment-related adverse events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three [1%] vs four [3%]).

INTERPRETATION

First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy.

FUNDING

F Hoffmann-La Roche and Genentech Inc, a member of the Roche group.

Author Affiliations

1Department of Oncology, University College London Hospitals NHS Foundation Trust, CRUK Lung Cancer Centre of Excellence and UCL Cancer Institute, London, UK;2Bereich Pneumologie Klinik und Poliklinik für Innere Medizin II, University Hospital Regensburg, Regensburg, Germany;3Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India;4Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland;5Department of Lung Diseases, Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy, Otwock, Poland;6Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China;7Department of Thoracic Oncology, LKI Lungenfachklinik Immenhausen, Immenhausen, Germany;8Department of Oncology, Royal Cornwall Hospitals NHS Trust, Truro, UK;9Medical Oncology Department, Hospital Universitario Virgen Macarena, Seville, Spain;10Department of Medical Oncology, The Christie NHS Foundation Trust and Division of Cancer Sciences, University of Manchester, Manchester, UK;11Department of Medical Oncology, AAST H S Gerardo Monza, Monza, Italy;12Cho Ray Cancer Centre, Cho Ray Hospital, Ho Chi Minh City, Viet Nam;13Department of Thoracic Oncology, National Clinical Research Centre for Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China;14Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada;15Department of Oncology, National Cancer Institute IRCCS Regina Elena, Rome, Italy;16Oncologico Potosino, San Luis Potosí, Mexico;17Department of Thoracic Oncology, Lungen Clinic Grosshansdorf, Airway Research Centre North, German Centre for Lung Research, Grosshansdorf, Germany;18Department of Medical Oncology, Catalan Institute of Oncology, Hospital Duran i Reynals, L’Hospitalet, Barcelona, Spain;19Department of Medical Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil;20F Hoffmann-La Roche, Basel, Switzerland;21Genentech, San Francisco, CA, USA;22Pfizer, Kent, UK;23Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Perioperative Nivolumab in Resectable Lung Cancer

Perioperative nivolumab (Nivo) showed a 20% 18-month EFPS improvement. This is another option to consider for your patients with stage IIA-IIIB NSCLC. Of note, the study arm received chemo + Nivo x 4 cycles preoperatively, then 12 months of Nivo therapy, and toxicities were as expected.

Read More »

Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer

FCS medical oncologist and hematologist Ernesto Bustinza-Linares, MD has co-authored an abstract published in the American Society of Clinical Oncology Journal, JCO Precision Oncology, that uncovers a new testing method to determine personalized care options for patients with metastatic non-small cell lung cancer (NSCLC). The abstract’s authors address the limitations of existing guidelines that recommend checkpoint immunotherapy, sometimes in combination with chemotherapy, for treating NSCLC, which often discounts patient variability and immune factors. The findings from the study show that by incorporating additional plasma proteome-based testing, combined with the standard protein inhibitor testing, clear differences in patient outcomes were observed after applying targeted treatments based on the testing results.

Read More »

Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04)

Adding VEGF inhibitor to PD-1 blocker in addition to chemotherapy is better than a chemotherapy-alone regimen as a second-line therapy after TKI failure. This is true especially in patients with tumors with high PD-L1 expression, with not much besides chemotherapy as second-line therapy for those patients (or other clinical trials) that may be a better option that includes immunotherapy.

Read More »

Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor–Mutated Metastatic Non–Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722

This is the same issue as the Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04) article, this one was negative though. A question for the previous trial would be: do we need PDL-1 inhibitor, or just VEGF inhibitor, recall the pts with tumors with high PDL-1 expression did better though, so most likely we need both with chemotherapy.

Read More »