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Relative dose intensity of first-line chemotherapy and overall survival in patients with advanced non-small-cell lung cancer.

ABSTRACT: PURPOSE:The effects of chemotherapy dose intensity on survival in patients with advanced non-small-cell lung cancer (NSCLC) are poorly understood. We retrospectively analyzed dose delays/reduction, relative dose intensity (RDI), and the association between chemotherapy intensity and survival in advanced NSCLC. METHODS:This retrospective cohort study included adults with advanced lung cancer who received first-line myelosuppressive platinum-based chemotherapy (January 2007-December 2010) in ~?230 US Oncology Network community practices. Dose delays ??7 days, dose reductions ??15%, and RDI relative to standard regimens were described. Overall survival (OS) was measured using Kaplan-Meier and Cox proportional hazard (PH) models. RESULTS:Among 3866 patients with advanced NSCLC, 32.4% experienced dose delays ??7 days, 50.1% experienced dose reductions ??15%, and 40.4% had RDI

SUBMITTER: Crawford J

PROVIDER: S-EPMC6954126 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Relative dose intensity of first-line chemotherapy and overall survival in patients with advanced non-small-cell lung cancer.

Crawford Jeffrey J Denduluri Neelima N Patt Debra D Jiao Xiaolong X Morrow Phuong Khanh PK Garcia Jacob J Barron Richard R Lyman Gary H GH

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 20190607 2

<h4>Purpose</h4>The effects of chemotherapy dose intensity on survival in patients with advanced non-small-cell lung cancer (NSCLC) are poorly understood. We retrospectively analyzed dose delays/reduction, relative dose intensity (RDI), and the association between chemotherapy intensity and survival in advanced NSCLC.<h4>Methods</h4>This retrospective cohort study included adults with advanced lung cancer who received first-line myelosuppressive platinum-based chemotherapy (January 2007-December ...[more]

PMID: 31172284

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Project description:BackgroundChemotherapy-induced toxicities lead to therapy dose reduction or delay, affecting patient outcomes. This systematic review and meta-analysis evaluated the impact of relative dose intensity (RDI) on survival in adult patients with solid tumor cancer on nonadjuvant-based chemotherapy regimens.MethodsPubMed, Embase, and Web of Science databases were searched for peer-reviewed English journal articles or congress abstracts evaluating association between RDI and survival; observational studies, case series of ≥20 patients, and clinical trials published between 2013 and 2020 were eligible. Meta-analyses were conducted to quantify the association between RDI levels and overall survival (OS) among studies reporting a hazard ratio (HR) for OS by similar tumor types, regimens, and RDI. Forest plots represented summary HR and 95% confidence interval (CI); Cochran's Q and I2 tests evaluated study heterogeneity.ResultsOverall, 919 articles were reviewed and 22 included; seven were eligible for meta-analysis. Significantly shorter OS at RDI <80% versus ≥80% and <85% versus ≥85% was observed upon meta-analysis of four carboplatin-based studies for breast, non-small cell lung, or ovarian cancer (HR 1.17; 95% CI: 1.07-1.27) and three FOLFOX-, FOLFIRI-, or FOLFIRINOX-based studies for colorectal or pancreatic cancer (HR 1.39; 95% CI: 1.03-1.89). Grade 3 or higher hematologic toxicities were higher for carboplatin-based regimens (thrombocytopenia: 14%-22%; anemia: 15%-19%; neutropenia: 24%-58%) than FOLFOX-, FOLFIRI-, or FOLFIRINOX-based regimens (thrombocytopenia: 1%-4%; anemia: 5%-19%; neutropenia: 19%-47%).ConclusionThe results suggested longer OS with RDI ≥80% or ≥85% for both regimens, indicating that management of toxicities across treatment modalities may contribute to maintenance of higher RDI and benefit survival for patients with advanced solid tumors.Implications for practiceChemotherapy-induced toxicities lead to dose reduction and/or treatment delay, thus affecting patient outcomes. Results of this systematic review and meta-analysis, evaluating the impact of relative dose intensity (RDI) on survival of patients with solid tumors on nonadjuvant-based chemotherapy regimens, demonstrate a longer overall survival with RDI levels of at least 80% for patients with solid tumors on carboplatin-based and FOLFOX-, FOLFIRI-, or FOLFIRINOX-based chemotherapy regimens, suggesting a protective effect of maintaining RDI ≥80% or ≥ -85%. Although grade 3 or higher hematologic toxicities occurred more in carboplatin-based studies, managing toxicities across treatment regimens may contribute to maintenance of higher RDI and ultimately benefit overall survival.

Project description:ImportanceThere is a need to tailor treatments to patients who are most likely to derive the greatest benefit from them to improve patient outcomes and enhance cost-effectiveness of cancer therapies.ObjectiveTo compare overall survival (OS) between patients with a current or former history of smoking with patients who never smoked and initiated pembrolizumab monotherapy as first-line (1L) treatment for advanced non-small lung cancer (NSCLC).Design, setting, and participantsThis retrospective cohort study compared patients diagnosed with advanced NSCLC aged 18 or higher selected from a nationwide real-world database originating from more than 280 US cancer clinics. The study inclusion period was from January 1, 2011, to October 1, 2019.ExposuresSmoking status at the time of NSCLC diagnosis.Main outcomes and measuresOS measured from initiation of 1L pembrolizumab monotherapy.ResultsIn this retrospective cohort study, a total of 1166 patients (median [IQR] age, 72.9 [15.3] years; 581 [49.8%] men and 585 [50.2%] women) were assessed in the primary analysis, including 91 patients [7.8%] with no history of smoking (ie, never-smokers) and 1075 patients [92.2%] who currently or formerly smoked (ie, ever-smokers). Compared with ever-smokers, never-smokers were older (median age [IQR] of 78.2 [12.0] vs 72.7 [15.5] years), more likely to be female (61 [67.0%] vs 524 [48.7%]) and to have been diagnosed with nonsquamous tumor histology (70 [76.9%] vs 738 [68.7%]). After adjustment for baseline covariates, ever-smokers who initiated 1L pembrolizumab had significantly prolonged OS compared to never-smokers (median OS: 12.8 [10.9-14.6] vs 6.5 [3.3-13.8] months; hazard ratio (HR): 0.69 [95% CI, 0.50-0.95]). This trend was observed across all sensitivity analyses for the 1L pembrolizumab cohort, but not for initiators of 1L platinum chemotherapy, for which ever-smokers showed significantly shorter OS compared with never-smokers (HR, 1.2 [95% CI, 1.07-1.33]).Conclusions and relevanceIn patients with advanced NSCLC who received 1L pembrolizumab monotherapy in routine clinical practices in the US, patients who reported a current or former history of smoking at the time of diagnosis had consistently longer OS than never-smokers. This finding suggests that in never-smoking advanced NSCLC, 1L pembrolizumab monotherapy may not be the optimal therapy selection, and genomic testing for potential genomically matched therapies should be prioritized over pembrolizumab in never-smokers.

Project description:Recently, it has been reported that the relative dose intensity (RDI) of adjuvant chemotherapy (AC) influences survival in various cancers, but there are very few reports about RDI in pancreatic ductal adenocarcinoma (PDAC). The optimal timing for initiation of AC for PDAC also remains unknown. The aim of this study was to identify the significance of RDI and the time interval between surgery and initiation of AC on survival of patients with PDAC. Clinicopathological factors that affect RDI were also investigated.A total of 311 consecutive PDAC patients who underwent curative resection between May 2005 and January 2015 were enrolled. Patients who underwent neoadjuvant chemoradiation, had UICC stage IV disease, or had early recurrences within 6 months were excluded, and the remaining 168 cases were analyzed.Patients with RDIs ≥80% (n = 79) showed significantly better overall survival (OS) compared to patients with RDIs <80% (n = 55) (median survival time (MST): 45.6 months, 26.0 months, P < 0.001). Patients with no AC (n = 34) showed the worst OS (MST: 20.8 months). Whether the AC was initiated earlier or later than 8 weeks after surgery did not influence survival, either in patients with RDIs ≥80% (P = 0.79) or in those with <80% (P = 0.73). Patients in the S-1 monotherapy group (n = 49) showed significantly better OS than patients in the gemcitabine monotherapy group (n = 51) (MST: 95.0 months, 26.0 months, respectively; P = 0.001). Univariate analysis conducted after adjusting for the chemotherapeutic drug used identified several prognostic factors; male gender (P = 0.01), intraoperative blood transfusion (P = 0.005), lymph node metastasis (P = 0.03), and postoperative WBC count (P = 0.03). Multivariate analysis identified intra-plus postoperative blood transfusion (P = 0.002) and high postoperative platelet-to-lymphocyte ratios (PLR) (P = 0.04) as independent predictors of poor RDI.Efforts to maintain RDI had a greater impact on survival than the struggle to start AC early after surgery. Intra-plus postoperative blood transfusion and a high postoperative PLR could be predictive markers of reduced RDI in AC of PDAC patients. Avoidance of perioperative blood transfusions where possible and nutritional support during the perioperative period could maintain adequate RDI and may lead to improved long-term outcome.

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Relative dose intensity of first-line chemotherapy and overall survival in patients with advanced non-small-cell lung cancer.

Publications

Relative dose intensity of first-line chemotherapy and overall survival in patients with advanced non-small-cell lung cancer.

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