PMID- 32951293 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20221213 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 26 IP - 3 DP - 2021 Mar TI - Expanding Beyond Maximum Grade: Chemotherapy Toxicity over Time by Age and Performance Status in Advanced Non-Small Cell Lung Cancer in CALGB 9730 (Alliance A151729). PG - e435-e444 LID - 10.1002/onco.13527 [doi] AB - BACKGROUND: Prior comparisons of chemotherapy adverse events (AEs) by age and performance status (PS) are limited by the traditional maximum grade approach, which ignores low-grade AEs and longitudinal changes. MATERIALS AND METHODS: To compare fatigue and neuropathy longitudinally by age (<65, >/=65 years) and PS (0-1, 2), we analyzed data from a large phase III trial of carboplatin and paclitaxel versus paclitaxel for advanced non-small cell lung cancer (CALGB 9730, n = 529). We performed multivariable (a) linear mixed models to estimate mean AE grade over time, (b) linear regression to estimate area under the curve (AUC), and (c) proportional hazards models to estimate the hazard ratio of developing grade >/=2 AE, as well as traditional maximum grade analyses. RESULTS: Older patients had on average a 0.17-point (95% confidence interval [CI], 0.00-0.34; p = .049) higher mean fatigue grade longitudinally compared with younger patients. PS 2 was associated with earlier development of grade >/=2 fatigue (hazard ratio [HR], 1.56; 95% CI, 1.07-2.27; p = .02). For neuropathy, older age was associated with earlier development of grade >/=2 neuropathy (HR, 1.41; 95% CI, 1.00-1.97; p = .049). Patients with PS 2 had a 1.30 point lower neuropathy AUC (95% CI, -2.36 to -0.25; p = .02) compared with PS 0-1. In contrast, maximum grade analyses only detected a higher percentage of older adults with grade >/=3 fatigue and neuropathy at some point during treatment. CONCLUSION: Our comparison of complementary but distinct aspects of chemotherapy toxicity identified important longitudinal differences in fatigue and neuropathy by age and PS that are missed by the traditional maximum grade approach. Clinical trial identification number: NCT00003117 (CALGB 9730) IMPLICATIONS FOR PRACTICE: The traditional maximum grade approach ignores persistent low-grade adverse events (AEs) and changes over time. This toxicity over time analysis of fatigue and neuropathy during chemotherapy for advanced non-small cell lung cancer demonstrates how to use longitudinal methods to comprehensively characterize AEs over time by age and performance status (PS). We identified important longitudinal differences in fatigue and neuropathy that are missed by the maximum grade approach. This new information about how older adults and patients with PS 2 experience these toxicities longitudinally may be used clinically to improve discussions about treatment options and what to expect to inform shared decision making and symptom management. CI - (c) AlphaMed Press 2020. FAU - Wong, Melisa L AU - Wong ML AUID- ORCID: 0000-0001-6390-6959 AD - Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA. AD - Division of Geriatrics, University of California, San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. FAU - Gao, Junheng AU - Gao J AD - Alliance Statistics and Data Center, Duke University, Durham, North Carolina, USA. FAU - Thanarajasingam, Gita AU - Thanarajasingam G AD - Department of Hematology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Sloan, Jeff A AU - Sloan JA AD - Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota, USA. FAU - Dueck, Amylou C AU - Dueck AC AD - Alliance Statistics and Data Center, Mayo Clinic, Scottsdale, Arizona, USA. FAU - Novotny, Paul J AU - Novotny PJ FAU - Jatoi, Aminah AU - Jatoi A AD - Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Hurria, Arti AU - Hurria A AD - Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA. FAU - Walter, Louise C AU - Walter LC AD - Division of Geriatrics, University of California, San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. FAU - Miaskowski, Christine AU - Miaskowski C AD - Department of Physiological Nursing, University of California, San Francisco, San Francisco, California, USA. FAU - Cohen, Harvey J AU - Cohen HJ AD - Center for the Study of Aging and Human Development, Duke University, Durham, North Carolina, USA. FAU - Wood, William A AU - Wood WA AD - Lineberger Comprehensive Cancer Center, Division of Hematology/Oncology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA. FAU - Feliciano, Josephine L AU - Feliciano JL AD - Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Center, Baltimore, Maryland, USA. FAU - Stinchcombe, Thomas E AU - Stinchcombe TE AD - Duke Cancer Institute, Duke University, Durham, North Carolina, USA. FAU - Wang, Xiaofei AU - Wang X AD - Alliance Statistics and Data Center, Duke University, Durham, North Carolina, USA. LA - eng GR - KL2 TR001870/TR/NCATS NIH HHS/United States GR - K76 AG064431/AG/NIA NIH HHS/United States GR - KL2 TR002379/TR/NCATS NIH HHS/United States GR - R03 AG056439/AG/NIA NIH HHS/United States GR - U10 CA180802/CA/NCI NIH HHS/United States GR - UG1 CA232760/CA/NCI NIH HHS/United States GR - UG1 CA233373/CA/NCI NIH HHS/United States GR - UG1 CA189823/CA/NCI NIH HHS/United States GR - UG1 CA233196/CA/NCI NIH HHS/United States GR - P30 CA033572/CA/NCI NIH HHS/United States GR - U10 CA180838/CA/NCI NIH HHS/United States GR - P30 AG044281/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20201001 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - BG3F62OND5 (Carboplatin) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Carboplatin/adverse effects MH - *Carcinoma, Non-Small-Cell Lung/drug therapy MH - Humans MH - *Lung Neoplasms/drug therapy MH - Paclitaxel/adverse effects PMC - PMC7930405 OTO - NOTNLM OT - Chemotherapy OT - Fatigue OT - Geriatric oncology OT - Lung cancer OT - Neuropathy COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2020/09/21 06:00 MHDA- 2021/06/22 06:00 PMCR- 2021/03/01 CRDT- 2020/09/20 20:42 PHST- 2020/05/06 00:00 [received] PHST- 2020/08/27 00:00 [accepted] PHST- 2020/09/21 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/09/20 20:42 [entrez] PHST- 2021/03/01 00:00 [pmc-release] AID - ONCO13527 [pii] AID - 10.1002/onco.13527 [doi] PST - ppublish SO - Oncologist. 2021 Mar;26(3):e435-e444. doi: 10.1002/onco.13527. Epub 2020 Oct 1.