Impact of frontline doublet versus triplet therapy on clinical outcomes: Exploratory analysis from the RAINBOW study.

Klempner, Samuel J.; Wainberg, Zev A.; Muro, Kei; Chao, Joseph; Catenacci, Daniel V.T.; Ajani, Jaffer A.; Al‐Batran, Salah‐Eddin; Toms, N.; Knoderer, Holly; Wei, Ran; Liepa, Astra M.; Chatterjee, Anindya; Ohtsu, Atsushi

doi:10.1200/jco.2020.38.15_suppl.4543

Cited by 3 publications

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“…For patients with advanced HER2‐negative G/GEA and a good performance status but who are not amenable to surgical resection, 1L recommended treatment options include FOLFOX or a combination of capecitabine plus oxaliplatin. The 2L RAINBOW study did not enroll patients with a prior docetaxel containing triplet therapy, and an exploratory analysis indicated increased toxicities with prior triplet compared with doublet therapies [88]. Given the improvements in OS in patients with favorable performance status using various 2L regimens, sequentially navigating patients to active 2L therapy as opposed to upfront triplets containing taxanes may provide survival benefits with less toxicity.…”

Section: Discussionmentioning

confidence: 99%

Toward a Treatment Sequencing Strategy: A Systematic Review of Treatment Regimens in Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

et al. 2021

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Background. Platinum and fluoropyrimidine combinations typically comprise first-line (1L) therapy in advanced gastric cancer or gastroesophageal junction adenocarcinoma (G/GEA), although controversy exists regarding the use of doublet versus triplet cytotoxic regimens. Historically, second-line (2L) and third-line or later (3L+) therapy has been fragmented. Recent trials have increased the need for optimal treatment sequencing in advanced G/GEA. Materials and Methods. We conducted a systematic search of peer-reviewed manuscripts of randomized clinical trials examining 1L, 2L, and 3L+ therapy for advanced G/GEA published from 2009 through November 19, 2019. When available, overall survival, progression-free survival, time to progression, overall response rate, and toxicity were extracted from each and compared descriptively.Results. In 1L therapy, chemotherapy triplets demonstrated variable efficacy improvements with invariable increased toxicity compared to platinum/fluoropyrimidine doublets. Currently, the only published report of positive outcomes using biologics in 1L is adding trastuzumab in HER2+ advanced G/GEA. In 2L, doublet chemotherapy regimens are not uniformly more efficacious than single-agent taxanes or irinotecan, and ramucirumab has demonstrated improved outcomes as both monotherapy or combination. Conclusion.For advanced G/GEA, review of trial results from 2009-2019 support 1L therapy with platinum and fluoropyrimidine and sequencing with taxanes or irinotecan in combination with biologics as effective 2L options. Escalating to a triplet may add some efficacy at the expense of added toxicity. The Oncologist 2021;9999:• • Implications for Practice: The rapidly changing treatment landscape for advanced gastric cancer includes increasing options for refractory disease. With multiple first-line platinum-based regimens, identification of those with the best benefit-to-risk ratio may provide guidance on treatment sequencing strategies. Herein, we present findings from the published literature of randomized controlled trials that included a first-line platinum/fluoropyrimidine combination and, for second-line trials, patients with platinum/fluoropyrimidine-refractory disease. This guiding summary could be a tool for clinicians to identify the optimal first-line regimen(s) followed by a strategy for subsequent regimens.

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Section: Discussionmentioning

confidence: 99%

Toward a Treatment Sequencing Strategy: A Systematic Review of Treatment Regimens in Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

et al. 2021

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“…Thus, it is surmised that not only the effect of elevated thyroid hormones on cancer cells themselves but that also the dysregulation of angiogenesis plays a major role in thyroid hormone-stimulated cancer progression. Particularly for gastroesophageal cancer, inhibition of angiogenesis in resectable as well as palliative settings is intensively studied and demonstrates promising outcomes [21,22]. However, it is suggested that not all patients obtain benefit from these treatment strategies and hence, an appropriate selection based on biomarkers would be helpful.…”

Section: Thyroid Hormone Statusmentioning

confidence: 99%

Thyroid Hormone Replacement Therapy Is Associated with Longer Overall Survival in Patients with Resectable Gastroesophageal Cancer: A Retrospective Single-Center Analysis

Puhr

Reiter

El-Mahrouk

et al. 2021

Cancers

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Introduction: As thyroid hormones modulate proliferative pathways it is surmised that they can be associated with cancer development. Since the potential association of gastroesophageal cancer and thyroid disorders has not been addressed so far, the aim of this study was to investigate the association of thyroid hormone parameters with the outcome of these patients, so novel prognostic and even potentially therapeutic markers can be defined. Material and Methods: Clinical and endocrinological parameters of patients with resectable gastroesophageal cancer treated between 1990 and 2018 at the Vienna General Hospital, Austria, including history of endocrinological disorders and laboratory analyses of thyroid hormones at first cancer diagnosis were investigated and correlated with the overall survival (OS). Results: In a total of 865 patients, a tendency towards prolonged OS in hypothyroid patients (euthyroid, n = 647: median OS 29.7 months; hyperthyroid, n = 50: 23.1 months; hypothyroid, n = 70: 47.9 months; p = 0.069) as well as a significant positive correlation of thyroid hormone replacement therapy with the OS was observed (without, n = 53: median OS 30.6 months; with, n = 67: 51.3 months; p = 0.017). Furthermore, triiodothyronine (T3) levels were also associated with the OS (median OS within the limit of normal: 23.4, above: 32.4, below: 9.6 months; p = 0.045). Conclusion: Thyroid disorders and their therapeutic interventions might be associated with the OS in patients with resectable gastroesophageal cancer. As data on the correlation of these parameters is scarce, this study proposes an important impulse for further analyses concerning the association of thyroid hormones with the outcome in patients with gastroesophageal tumors.

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“…Однако, согласно результатам эксплоративного анализа данных исследования RAINBOW, интенсивность режима 1-й линии лечения не оказывает влияния на эффективность 2-й линии лечения с рамуцирумабом [26].…”

Section: обсуждение полученных результатовunclassified

Analysis of prognostic factors for survival in the Russian population of patients with disseminated gastric cancer, who received ramucirumab as secondline therapy in the RAMSELGA trial

Бесова¹,

Титова²,

Артамонова

et al. 2020

Medicinskij sovet

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Background. Ramucirumab is a monoclonal antibody that inhibits the vascular endothelial growth factor receptor-2 (VEGFR2). The study is aimed to analyse prognostic factors for survival in patients with disseminated gastric cancer who received ramucirumab in the second-line therapy in ’real-life’ clinical setting of Russia (RAMSELGA). Methods. We retrospectively analysed the outcome of 163 patients aged 20–78 years from 11 oncological centres in Russia. Survival analysis was performed using the Kaplan – Meier model, and regression analysis was performed using the Cox model. Results. In a univariate analysis of overall survival, 5 factors were identified as independent factors of an unfavourable prognosis: 1) age <65 years (RR 0.542; 95% CI 0.302–0.971; p = 0.039); 2) time to tumour progression on the first-line therapy is not more than four months. (RR 0.161; 95% CI 0.105–0.246; p = 0.0000); 3) a low grade tumour or colloid cancer (RR 1,868; 95% CI 1,063–3,284; p = 0,030); 4) peritoneal metastasis (RR 1.549; 95% CI 1.026–2.339; p = 0.037); 5) ascites or pleurisy (RR 0.624; 95% CI 0.424–0.920; p = 0.017). In a multivariate analysis, favourable prognostic factors of overall survival of patients included age – 65 years or older (OS 2.288; 95% CI 1.240–4.220; p = 0.008) and time to tumour progression on the first-line therapy – more than 4 months (OS 6.650; 95% CI 4.221–10.477; p = 0.000). Conclusion. Despite an active search, prognostic factors for survival in patients that are universal for dGC have not yet been found. To build a universal prognostic model, a very thoughtful analysis considering not only clinical and laboratory, but also pathomorphological and molecular genetic characteristics is required.

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Impact of frontline doublet versus triplet therapy on clinical outcomes: Exploratory analysis from the RAINBOW study.

Cited by 3 publications

References 0 publications

Toward a Treatment Sequencing Strategy: A Systematic Review of Treatment Regimens in Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

Toward a Treatment Sequencing Strategy: A Systematic Review of Treatment Regimens in Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

Thyroid Hormone Replacement Therapy Is Associated with Longer Overall Survival in Patients with Resectable Gastroesophageal Cancer: A Retrospective Single-Center Analysis

Analysis of prognostic factors for survival in the Russian population of patients with disseminated gastric cancer, who received ramucirumab as secondline therapy in the RAMSELGA trial

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