Investigation of poor predictive factors in extensive stage small cell lung cancer under etoposide‐platinum‐atezolizumab treatment

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Abstract

Background

The phase III trial IMpower133 showed that platinum and etoposide plus atezolizumab was associated with improved overall survival (OS) and progression free‐survival (PFS) when compared to the placebo group in treatment‐naïve extensive stage (ES) small cell lung cancer (SCLC). Due to superiority in clinical outcomes, combination immunotherapy plus chemotherapy have become mainstay treatment modalities as first‐line treatment in ES‐SCLC. Nevertheless, real‐world data are still lacking and the search for potential biomarkers is essential. This study aimed to evaluate potential predictive biomarkers applicable in ES‐SCLC under combination therapy.

Methods

Patients with ES‐SCLC under etoposide‐platinum‐atezolizumab enrolled from seven university hospitals affiliated to the Catholic University of Korea were evaluated. Pretreatment clinical parameters were evaluated for association with OS and PFS. Adverse events (AEs) during induction and maintenance phases were also evaluated. p‐values below 0.05 were considered statistically significant.

Results

A total of 41 patients were evaluated. Six‐month survival was 68.6%. As best response to treatment, 26 (63.4%) showed partial response, nine (22.0%) showed stable disease, and four (9.8%) showed progressive disease. During the induction phase, grade I–II AEs occurred in 22 (53.7%) patients, and grade III–IV AEs occurred in 26 (63.4%) patients. During the maintenance phase, nine out of 25 (36.0%) patients experienced any grade AEs. In multivariate analysis for OS, lactate dehydrogenase (LDH), c‐reactive protein (CRP), and forced vital capacity (%) were significant factors. In multivariate analysis for PFS, sex, and LDH were significant.

Conclusion

In ES‐SCLC under etoposide‐platinum‐atezolizumab, pretreatment CRP, LDH and FVC (%) were independent predictive factors.

Abstract

In ES‐SCLC under etoposide‐platinum‐atezolizumab, 6‐month survival was 68.6%. In survival analysis for OS, lactate dehydrogenase (LDH), c‐reactive protein (CRP), and forced vital capacity (%) were significant factors. In multivariate analysis for PFS, sex, and LDH were significant.

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Most cited references 32

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Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)

This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.

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New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

E A Eisenhauer, P Therasse, J. Bogaerts … (2009)

Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.

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First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

Leora Horn, Aaron Mansfield, Aleksandra Szczęsna … (2018)

Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy.

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Author and article information

Contributors

Hye Seon Kang:

ORCID: https://orcid.org/0000-0002-2096-7679

beyer_kr@catholic.ac.kr

Journal

Journal ID (nlm-ta): Thorac Cancer

Journal ID (iso-abbrev): Thorac Cancer

Journal ID (doi): 10.1111/(ISSN)1759-7714

Journal ID (publisher-id): TCA

Title: Thoracic Cancer

Publisher: John Wiley & Sons Australia, Ltd (Melbourne )

ISSN (Print): 1759-7706

ISSN (Electronic): 1759-7714

Publication date (Electronic): 23 October 2022

Publication date (Print): December 2022

Volume: 13

Issue: 23 ( doiID: 10.1111/tca.v13.23 )

Pages: 3384-3392

Affiliations

[ ¹ ] Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul Republic of Korea

[ ² ] Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul Republic of Korea

[ ³ ] Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul Republic of Korea

[ ⁴ ] Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul Republic of Korea

[ ⁵ ] Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine St. Vincent's Hospital, College of Medicine, The Catholic University of Korea Seoul Republic of Korea

[ ⁶ ] Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul Republic of Korea

[ ⁷ ] Division of Pulmonology, Department of Internal Medicine Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul Republic of Korea

[ ⁸ ] Postech‐Catholic Biomedical Engineering Institute Songeui Multiplex Hall, College of Medicine, The Catholic University of Korea Seoul Republic of Korea

Author notes

[*] [* ] Correspondence

Hye Seon Kang, Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 327, Sosa‐ro, Bucheon‐si, Gyeonggi‐do 14647, Republic of Korea.

Email: beyer_kr@ 123456catholic.ac.kr

Author information

Hye Seon Kang https://orcid.org/0000-0002-2096-7679

Chang Dong Yeo https://orcid.org/0000-0002-4103-7921

Seung Joon Kim https://orcid.org/0000-0003-4836-8958

Article

Publisher ID: TCA14697

DOI: 10.1111/1759-7714.14697

PMC ID: 9715810

PubMed ID: 36274214

SO-VID: ffd62b9e-6ce9-49d7-81dd-44d9a74768b3

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

History

Date revision received : 02 October 2022

Date received : 08 August 2022

Date accepted : 03 October 2022

Page count

Figures: 4, Tables: 5, Pages: 9, Words: 5442

Funding

Funded by: National Research Foundation of Korea , doi 10.13039/501100003725;

Award ID: NRF‐2021R1A2C2009932

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cover-date December 2022

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.1 mode:remove_FC converted:01.12.2022

Investigation of poor predictive factors in extensive stage small cell lung cancer under etoposide‐platinum‐atezolizumab treatment

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Abstract

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Cancer Immunotherapy

Most cited references 32

Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

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