Survival in Advanced Esophagogastric Adenocarcinoma Improves With Use of Multiple Lines of Therapy: Results From an Analysis of More Than 500 Patients

Davidson, Michael; Cafferkey, Catherine; Goode, E.; Kouvelakis, Kyriakos; Hughes, D.J.; Reguera, Pablo; Kalaitzaki, Eleftheria; Peckitt, Clare; S, Rao; Watkins, David; Chau, Ian; Cunningham, David; Starling, Naureen

doi:10.1016/j.clcc.2018.05.014

Cited by 31 publications

(44 citation statements)

References 35 publications

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“…19 More recently, an observational analysis of data from a single center in the United Kingdom (2009-2015) reported that only 39% of patients who received 1L chemotherapy for advanced GC/GEJC/ esophageal cancer subsequently received 2L therapy, and only 14% received 3L therapy. 20 The observation that only approximately 50% of patients with advanced/metastatic GC/GEJC progressed from 1L therapy to subsequent 2L therapy are similar to real-world findings in patients receiving treatment for other solid tumors. 21 Our analysis supports these previous observations, but also includes data until April 2018, reflecting ongoing research and consequent updates to clinical guidelines in recent years.…”

Section: Discussionmentioning

confidence: 62%

Real-world Treatment Patterns and Clinical Outcomes Across Lines of Therapy in Patients With Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer

Ott

Korytowsky

et al. 2020

Clinical Colorectal Cancer

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We explored treatment patterns and outcomes in 3291 real-world patients with advanced/metastatic gastric cancer and gastroesophageal junction cancer. Of these, 75% received first-line therapy, 32% received secondline therapy, 14% received third-line therapy, and 6% received at least 4 lines of therapy (median overall survival: 10.7, 7.6, 6.1, and 2.8 months, respectively). One-quarter of patients received no active treatment after diagnosis. Background: First-line (1L) and second-line (2L) therapies for advanced/metastatic gastric cancer (GC) and gastroesophageal junction cancer (GEJC) have modest efficacy, and therapeutic options in subsequent lines are limited as disease progresses. We assessed real-world treatment patterns and outcomes for advanced/metastatic GC/GEJC. Patients and Methods: Adult patients diagnosed with advanced/metastatic GC/GEJC between January 1, 2011 and April 30, 2018 were identified using the Flatiron Health database. Median overall survival (OS) from start of each line of therapy until death was estimated by the Kaplan-Meier method. Duration of therapy (DoT) was time from start date until end date of each line. Results: We identified 3291 patients with advanced/metastatic GC/GEJC adenocarcinoma. At diagnosis, the median age was 68 years, 60% were white, 53% had initial stage IV disease, and 57% had GC. Of these 3291 patients, most (75%) received at least 1 therapy; 32% received 2L, 14% received third-line (3L) therapy, and 6% received at least 4 lines of therapy (4Lþ). The median OS from start of 1L was 10.7 months (2L, 7.6 months; 3L, 6.1 months; 4Lþ, 2.8 months). The median DoT in 1L was 2.2 months (2L, 2.1 months; 3L, 1.7 months; 4Lþ, 3.0 months). Use of targeted and immunotherapies generally increased progressively with each subsequent line of therapy. Conclusion: One-quarter of patients with advanced/metastatic GC/GEJC remained untreated, and only approximately one-half of patients receiving 1L therapy received subsequent treatment. In all lines of therapy, OS was generally poor and DoT was short. More effective treatment options are needed across all lines of therapy for this highly burdensome disease.

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Section: Discussionmentioning

confidence: 62%

Real-world Treatment Patterns and Clinical Outcomes Across Lines of Therapy in Patients With Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer

Ott

Korytowsky

et al. 2020

Clinical Colorectal Cancer

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“… 10 The above prospective randomized clinical trials have confirmed the survival advantages of second-line or third-line chemotherapy compared with their respective control groups. In Western countries, the proportion of AGC patients receiving second-line and third-line chemotherapy is 39–42% and 14–19%, respectively, 15 , 16 , 25 while in Japan, the proportion is even higher, 69–85% and 23–35%, respectively. 26 , 27 This difference has important implications for the survival of AGC patients.…”

Section: Discussionmentioning

confidence: 99%

“…The authors found that the median OS from diagnosis was 8.32, 13.95, 20.01, and 33.03 months for patients receiving 1, 2, 3 or >3 lines of chemotherapy, respectively (P<0.001). 25 As the number of chemotherapy lines increased, OS was gradually prolonged. In this study, we increased the survival data of AGC patients who did not receive chemotherapy, and found that the OS of patients with chemotherapy lines of 0,1,2 and ≥3 were 3.3, 8.6, 15.6, and 21.0 months, respectively (P<0.001).…”

Section: Discussionmentioning

confidence: 99%

<p>Outcomes of 596 Advanced Gastric Cancer Patients with Different Numbers of Chemotherapy Lines: The More Chemotherapy Lines, the Better Survival</p>

Sun

Wang

Liu

et al. 2020

CMAR

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Objective Many large-sample prospective randomized clinical trials investigating advanced gastric cancer (AGC) have confirmed the survival advantages of first-line, second-line, or third-line chemotherapy compared with their respective control groups. However, due to the ethical concerns of prospective clinical trials, it is impossible to conduct a randomized comparative study of patients who do not receive chemotherapy and those who receive a second-line or above chemotherapy. Few research reports have addressed the relationship between the number of chemotherapy lines and overall survival (OS) in patients with AGC. In the present study, we analyzed the impact of the number of chemotherapy lines on OS in AGC patients using real-world data. Patients and Methods This study collected the medical records of patients with AGC diagnosed at Shandong Cancer Hospital from December 2007 to December 2017. According to the treatment received, AGC patients were divided into groups that did not receive chemotherapy, those who received only 1 line, 2 lines, or 3 lines and above. Kaplan–Meier analysis was used to assess patient survival. Results A total of 596 AGC patients were included in this study. The following patients were enrolled: 0 lines (did not receive chemotherapy), 77 (12.9%); 1 line, 235 (39.4%) patients; 2 lines, 185 (31.1%) patients; and ≥3 lines 99 (16.6%) patients. OS was significantly correlated with the number of chemotherapy lines (P<0.001), with a median OS from diagnosis of 3.3, 8.6, 15.6, and 21.0 months for patients receiving 0, 1, 2, ≥3 lines of chemotherapy, respectively. Conclusion This study showed that the more chemotherapy lines AGC patients received, the longer the OS. This study not only confirmed the impact of chemotherapy lines on OS but it also supplements the results of prospective clinical trials that cannot be completed due to the ethical implications.

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“…Because of the poor prognosis of GEA with first-line therapy, the majority of patients do not receive third-line and later therapies. 4 , 36 - 38 The monotherapy activity of bemarituzumab and its lack of significant overlapping toxicities with standard platinum and fluoropyrimidine chemotherapeutic agents suggest that combining bemarituzumab with chemotherapy may potentially benefit more patients in the front-line setting of FGFR2b-overexpressing GEA. Early safety data suggest that bemarituzumab combined with oxaliplatin, fluorouracil, and leucovorin (mFOLFOX6) is tolerable in patients with advanced-stage GI cancers, 39 and a randomized, placebo-controlled, phase III study of mFOLFOX6 with bemarituzumab in patients with newly diagnosed advanced-stage GEA, the FIGHT trial (ClinicalTrials.gov identifier: NCT03694522 ), initiated enrollment in September 2018.…”

Section: Discussionmentioning

confidence: 99%

Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients With Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma

Catenacci

Rasco

Lee

et al. 2020

JCO

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PURPOSE To evaluate the safety, pharmacokinetics, and preliminary activity of bemarituzumab in patients with FGFR2b-overexpressing gastric and gastroesophageal junction adenocarcinoma (GEA). PATIENTS AND METHODS FPA144-001 was a phase I, open-label, multicenter trial consisting of the following 3 parts: part 1a involved dose escalation in patients with recurrent solid tumors at doses ranging from 0.3 to 15 mg/kg; part 1b involved dose escalation in patients with advanced-stage GEA; and part 2 involved dose expansion in patients with advanced-stage GEA that overexpressed FGFR2b at various levels (4 cohorts; high, medium, low, and no FGFR2b overexpression) and 1 cohort of patients with FGFR2b-overexpressing advanced-stage bladder cancer. RESULTS Seventy-nine patients were enrolled; 19 were enrolled in part 1a, 8 in part 1b, and 52 in part 2. No dose-limiting toxicities were reported, and the recommended dose was identified as 15 mg/kg every 2 weeks based on safety, tolerability, pharmacokinetic parameters, and clinical activity. The most frequent treatment-related adverse events (TRAEs) were fatigue (17.7%), nausea (11.4%), and dry eye (10.1%). Grade 3 TRAEs included nausea (2 patients) and anemia, neutropenia, increased AST, increased alkaline phosphatase, vomiting, and an infusion reaction (1 patient each). Three (10.7%) of 28 patients assigned to a cohort receiving a dose of ≥ 10 mg/kg every 2 weeks for ≥ 70 days reported reversible grade 2 corneal TRAEs. No TRAEs of grade ≥ 4 were reported. Five (17.9%; 95% CI, 6.1% to 36.9%) of 28 patients with high FGFR2b-overexpressing GEA had a confirmed partial response. CONCLUSION Overall, bemarituzumab seems to be well tolerated and demonstrated single-agent activity as late-line therapy in patients with advanced-stage GEA. Bemarituzumab is currently being evaluated in combination with chemotherapy in a phase III trial as front-line therapy for patients with high FGFR2b-overexpressing advanced-stage GEA.

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Survival in Advanced Esophagogastric Adenocarcinoma Improves With Use of Multiple Lines of Therapy: Results From an Analysis of More Than 500 Patients

Cited by 31 publications

References 35 publications

Real-world Treatment Patterns and Clinical Outcomes Across Lines of Therapy in Patients With Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer

Real-world Treatment Patterns and Clinical Outcomes Across Lines of Therapy in Patients With Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer

<p>Outcomes of 596 Advanced Gastric Cancer Patients with Different Numbers of Chemotherapy Lines: The More Chemotherapy Lines, the Better Survival</p>

Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients With Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma

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