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. 2023 Dec 25;5(4):100626.
doi: 10.1016/j.jtocrr.2023.100626. eCollection 2024 Apr.

Checkpoint Inhibitor Monotherapy in Potentially Trial-Eligible or Trial-Ineligible Patients With Metastatic NSCLC in the German Prospective CRISP Registry Real-World Cohort (AIO-TRK-0315)

Frank Griesinger  1 , Martin Sebastian  2 , Wolfgang M Brueckl  3 , Horst-Dieter Hummel  4 , Bastian Jaeschke  5 , Jens Kern  6 , Claas Wesseler  7 , Martina Jänicke  8 , Annette Fleitz  8 , Stefan Zacharias  9 , Annette Hipper  10 , Annika Groth  10 , Wilko Weichert  11 , Steffen Dörfel  12 , Volker Petersen  13 , Jan Schröder  14 , Jochen Wilke  15 , Wilfried E E Eberhardt  16   17 , Michael Thomas  18 ; CRISP Registry Group
Collaborators, Affiliations

Checkpoint Inhibitor Monotherapy in Potentially Trial-Eligible or Trial-Ineligible Patients With Metastatic NSCLC in the German Prospective CRISP Registry Real-World Cohort (AIO-TRK-0315)

Frank Griesinger et al. JTO Clin Res Rep. .

Abstract

Introduction: Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of "trial-ineligible" and "potentially trial-eligible" patients.

Methods: Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either "potentially trial-eligible" or "trial-ineligible" according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042).

Results: Of 746 patients included, 343 patients (46.0%) were classified as "trial-ineligible" and had significantly worse outcomes compared with "potentially trial-eligible" patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2-8.4) versus 10.3 (95% CI: 8.4-13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19-1.72), p less than 0.001; median overall survival: 15.9 (95% CI: 11.4-20.3) versus 25.3 (95% CI: 19.8-30.4) months, hazard ratio of 1.36 (95% CI: 1.10-1.67), p equals 0.004.

Conclusions: Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses.

Keywords: Immune checkpoint inhibitors; Non–small cell lung carcinoma; Pembrolizumab; Prospective studies.

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Conflict of interest statement

Dr. Griesinger has received support for the present manuscript (grants to the institution) from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda. Furthermore, he has received grants (to the institution) from Amgen and Siemens; personal fees for consulting from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda; payment for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda; support for attending meetings and/or travel from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda; and personal fees for participation on a data safety monitoring board or advisory board from Merck Sharp & Dohme. He declares an unpaid fiduciary role in the German Society of Hematology and Oncology (first author of Oncopedia recommendations) and in the German Cancer Society (S3 guidelines author). Dr. Sebastian has a consulting or advisory role and has received honoraria from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen-Cilag, Eli Lilly, Merck Sharp & Dohme, Merck-Serono, Novartis, Pfizer, Roche, Takeda, and Tesaro; he has also received research funding from AstraZeneca. Dr. Brueckl has received personal fees and fees for lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, and Roche and fees for educational events from AstraZeneca, Boehringer, Eli Lilly, Pfizer, and Roche. Furthermore, he has received congress fees and personal fees from AstraZeneca, Boehringer, and Roche Pharma and has received personal fees and support for participation on advisory boards from AstraZeneca, Boehringer, Bristol-Myers Squibb, Eli Lilly Pharma, Novartis, Merck Sharp & Dohme and Roche. He declares a patent planned (EP21183549). Dr. Hummel has received personal fees as steering board member and fees for consulting from Amgen; has received personal fees for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, Bristol-Myers Squibb, and Boehringer Ingelheim; payment for expert testimony from Amgen and Boehringer Ingelheim; support for attending meetings and/or travel from Amgen and Bristol-Myers Squibb; and personal fees for participation on a data safety monitoring board or advisory board from Amgen and Boehringer Ingelheim. Dr. Kern has received support for attending meetings and/or travel from AstraZeneca, Merck Sharp & Dohme, Pfizer, and Roche and for participation on advisory boards from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck/Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda. Dr. Wesseler has received honoraria for lectures and travel from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and Takeda. Dr. Hipper and Mrs. Groth have received research funding (to their employer AIO-Studien-gGmbH) from Amgen Ltd., AstraZeneca GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Bristol-Myers Squibb GmbH & Co. KGaA, Celgene GmbH, GlaxoSmithKline Research & Development Limited, Janssen-Cilag GmbH, Eli Lilly Deutschland GmbH, Merck Sharp & Dohme GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, Roche Pharma AG, and Takeda Pharma Vertriebs GmbH & Co. KG. Dr. Weichert has received research support (to the institution) from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Roche; fees for consulting, travel support, fees for participation on advisory boards and lectures, and payment or honoraria for presentations, speakers bureaus, manuscript writing, or educational events from ADC, Agilent, Amgen, Astellas, AstraZeneca, Bayer, Boehringer, Bristol-Myers Squibb, Eisai, GlaxoSmithKline, Illumina, Janssen, Eli Lilly, Merck, Molecular Health, Merck Sharp & Dohme, Novartis, Pfizer, Siemens, Takeda, and Roche. Mr. Dörfel holds iOMEDICO shares. Dr. Schröder has received consulting fees from iOMEDICO, Celgene, Roche, Bristol-Myers Squibb, Clovis Oncology GmbH, GlaxoSmithKline, Boehringer Ingelheim, Amgen, Novartis, Merck Sharp & Dohme, AOP, Searchlight, Pharma Partner, Medixline GmbH, Eisai, HE Research GmbH, AbbVie, NIO, I+E Research, Octapharma and IPSEN. Further he declares honoraria from iOMEDICO, Celgene, Roche, Bristol-Myers Squibb, Clovis Oncology GmbH, GlaxoSmithKline, Boehringer Ingelheim, Amgen, Novartis, Merck Sharp & Dohme, AOP, Searchlight, Pharma Partner, Medixline GmbH, Eisai, HE Research GmbH, AbbVie, NIO, I+E Research, Octapharma, IPSEN, BeiGene, and Miltenyi. Dr. Eberhardt has received research funding (to the institution) from Eli Lilly, AstraZeneca, and Bristol-Myers Squibb; honoraria for advisory boards from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Janssen-Cilag, Merck/Merck Sharp & Dohme, Roche, Pfizer, Novartis, Takeda, Boehringer Ingelheim, and AbbVie; and honoraria for lectures from Amgen, Baumgart Consult, Bristol-Myers Squibb, Merck/Merck Sharp & Dohme, Roche, Pfizer, Novartis, Takeda, Boehringer Ingelheim, and AbbVie. Dr. Thomas has received research funding (to the institution) from AstraZeneca, Bristol-Myers Squibb, Merck, Roche, and Takeda; personal fees for speakers bureaus and advisory boards from Amgen, AstraZeneca, Beigene, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Daiichi Sankyo, GlaxoSmithKline, Janssen Oncology, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and Takeda; and support for attending meetings and/or travel from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Janssen Oncology, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and Takeda. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart. Patient flow chart of all patients with metastatic stage IV NSCLC included in this analysis, starting from the total number of patients recruited into the CRISP registry from December 2015 to June 2022. Patients with TPS greater than or equal to 50% and first-line pembrolizumab monotherapy who had been followed-up for at least 12 months were classified as potentially trial-eligible when all the following criteria were met: ECOG performance status = 0 or 1, no brain metastases at inclusion, no HIV or second tumor, no prior (neo-)adjuvant therapies less than 6 months before diagnosis of first metastasis. Otherwise, patients were classified as trial-ineligible. ECOG, Eastern Cooperative Oncology Group; HIV, human immunodeficiency virus; TPS, tumor proportion score.
Figure 2
Figure 2
Survival analysis. (A) First-line registry-PFS and (B) first-line OS in all patients with metastatic NSCLC with TPS greater than or equal to 50% and first-line pembrolizumab monotherapy who had been followed-up for at least 12 months (total) and classified by trial-eligibility status. OS, overall survival; PFS, progression-free survival; Pot., potentially; TPS, tumor proportion score.
Figure 3
Figure 3
Regression analysis. Cox proportional hazards model for (A) PFS and (B) OS, respectively. OS, overall survival; PFS, progression-free survival.
Figure 4
Figure 4
Change in health-related quality of life and reported anxiety/depression from baseline to month 15. Mean change from baseline plots (mean ± 95% CI) for the FACT-G subscales (A) physical well-being, (B) social well-being, (C) emotional well-being, (D) functional well-being, and the (E) lung cancer subscale LCS, and for the (F) FACT-L total scale. For better readability, a line graph format was chosen; however, individual data points are found and not a change over time. Proportion of probable cases of (G) depression and (H) anxiety for potentially trial-eligible and ineligible patients. Change from baseline is calculated as mean of the individual difference between baseline and respective time point for all patients with data available at baseline and the respective time points. Probable cases of depression (PHQ-2) or anxiety (GAD-2) are defined as a score greater than or equal to 3 on the respective scale at the respective time point. CI, confidence interval; FACT-G/-L Functional Assessment of Cancer Therapy-General/-Lung; GAD-2, Generalized Anxiety Disorder Scale-2; LCS, lung cancer subscale; PHQ-2, Patient Health Questionnaire-2; pot., potentially.
See this image and copyright information in PMC

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