Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial

Shitara, Kohei; Takashima, Atsuo; Fujitani, Kazumasa; Koeda, Keisuke; Hara, Hiroki; Nakayama, Norisuke; Hironaka, Shuichi; Nishikawa, Kazuhiro; Makari, Yoichi; Amagai, Kenji; Ueda, Shinya; Yoshida, Kazuhiro; Shimodaira, Hideki; Nishina, Tomohiro; Tsuda, Masahiro; Kurokawa, Yukinori; Tamura, Takao; Sasaki, Yasutsuna; Morita, Satoshi; Koizumi, Wasaburo

doi:10.1016/s2468-1253(16)30219-9

Cited by 151 publications

(137 citation statements)

References 21 publications

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“…A subgroup analysis of the ABSOLUTE trial suggested that w-nab-PTX showed more favorable efficacy than w-sb-PTX in patients with peritoneal metastasis. Furthermore, the effect of w-nab-PTX was correlated with the amount of ascites [1]. W-nab-PTX is speculated to have advantages over w-sb-PTX depending on the severity of peritoneal metastasis.…”

Section: Introductionmentioning

confidence: 98%

Peritoneal metastasis as a predictive factor for nab-paclitaxel in patients with pretreated advanced gastric cancer: an exploratory analysis of the phase III ABSOLUTE trial

et al. 2018

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Background In the ABSOLUTE trial, weekly nanoparticle albumin-bound paclitaxel (w-nab-PTX) showed non-inferiority to weekly solvent-based paclitaxel (w-sb-PTX) for overall survival (OS). Thus, w-nab-PTX might be an option for secondline chemotherapy in advanced gastric cancer (AGC). However, predictive factors for efficacies of these agents have not been evaluated. Methods Patients previously enrolled in the ABSOLUTE trial were divided into apparent peritoneal metastasis group (PM group) and no apparent peritoneal metastasis group (no PM group) based on baseline imaging evaluated by RECIST ver. 1.1 criteria and amount of ascites. OS, progression-free survival, and overall response rate were compared between two arms in each group. Results This study included 240 and 243 patients in the w-nab-PTX and w-sb-PTX arms, respectively. In the PM group, the w-nab-PTX arm (n = 88) had longer OS than the w-sb-PTX arm (n = 103), and median survival time (MST) of 9.9 and 8.7 months [hazard ratio (HR) 0.63; 95% CI 0.45-0.88; P = 0.0060], respectively. In the no PM group, the w-nab-PTX arm (n = 140) had shorter OS than the w-sb-PTX arm (n = 152), and MST of 11.6 and 15.7 months (HR 1.40; 95% CI 1.06-1.86; P = 0.0180), respectively. After adjusting for prognostic factors, the HR for OS in the w-nab-PTX arm versus the w-sb-PTX arm was 0.59 (95% CI 0.42-0.83; P = 0.0023; PM group) and 1.34 (95% CI 1.01-1.78; P = 0.0414; no PM group), with significant interaction between treatment efficacy and presence of peritoneal metastasis (P = 0.0003). Conclusions The presence of apparent peritoneal metastasis might be a predictive factor for selecting w-nab-PTX for pretreated AGC patients. Trial registration number JapicCTI-132059.

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Section: Introductionmentioning

confidence: 98%

Peritoneal metastasis as a predictive factor for nab-paclitaxel in patients with pretreated advanced gastric cancer: an exploratory analysis of the phase III ABSOLUTE trial

et al. 2018

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“…There seemed to be a correlation between the dose schedule and rate of grade 3 to 4 peripheral neuropathy. The three‐weekly Nab‐PTX (260 mg/m 2 ) dose yielded 7%‐23.6% grade 3 to 4 peripheral neuropathy, significantly higher than paclitaxel . Weekly Nab‐PTX (100 mg/m 2 ) yielded 3%, significantly lower than paclitaxel, 3/4 weekly Nab‐PTX (125 mg/m 2 on d1, d8, and d15, q4w) yielded 17%, significantly higher than paclitaxel, whereas 3/4 weekly Nab‐PTX (100 mg/m 2 on d1, d8, and d15, q4w) yielded 2%, non‐inferior to paclitaxel .…”

Section: Discussionmentioning

confidence: 97%

“…Dose schedules of Nab‐PTX varied across phase I to III trials, and three‐weekly 260 mg/m 2 doses were used in breast and gastric cancers . The ABSOLUTE trial that explored 3/4 weekly Nab‐PTX (100 mg/m 2 on d1, d8, and d15, q4w) was non‐inferior to weekly solvent‐based paclitaxel as second‐line treatment of gastric cancer, which added evidence for divided doses of Nab‐PTX . Based on the dose‐escalation of Nab‐PTX with divided doses in combination with standard S‐1, in the present study, we use the recommended dose for Nab‐PTX 120 mg/m 2 on d1 and d8, q3w, achieving an efficacy/toxicity balance.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, Nab‐PTX has been approved as a second‐line option for AGC in Japan . A randomized phase III ABSOLUTE trial showed that 3/4 weekly Nab‐PTX (100 mg/m 2 , on days 1, 8, and 15, q4w) was non‐inferior to weekly solvent‐based paclitaxel in terms of overall survival, with a similar safety profile and a lower incidence of hypersensitivity reactions, and the advantages of the Nab‐PTX formulation make it a potential regimen for second‐line treatment of gastric cancer . The safety of S‐1 plus Nab‐PTX was confirmed in a phase I study of metastatic breast cancer .…”

Section: Introductionmentioning

confidence: 99%

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Phase II clinical trial of S‐1 plus nanoparticle albumin‐bound paclitaxel in untreated patients with metastatic gastric cancer

Wang

Jin

et al. 2018

Cancer Science

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The present study is the first phase II clinical trial aimed to evaluate the efficacy and safety of S‐1 plus nanoparticle albumin‐bound paclitaxel (Nab‐PTX) as first‐line chemotherapy for advanced gastric cancer (AGC). Previously untreated patients with metastatic gastric adenocarcinoma received S‐1 in oral doses of 40 mg (BSA <1.25 m2), 50 mg (1.25 ≤ BSA < 1.50 m2) and 60 mg (BSA ≥1.50 m2) b.i.d. on days 1‐14 in combination with Nab‐PTX (120 mg/m2, on days 1 and 8) for each 21‐day cycle. Primary endpoint was progression‐free survival (PFS), and secondary endpoints were overall response rate (ORR), overall survival (OS), disease control rate (DCR), and toxicity. A total of 73 gastric cancer patients with metastatic and measurable lesions were enrolled in the first‐line setting. Median PFS and OS were 9.63 months and 14.60 months, respectively. Four (5.5%) patients had complete responses, 39 (53.4%) had partial responses (PRs), 21 (28.8%) had stable disease, four (5.5%) progressed and five (6.8%) were not evaluable. ORR and DCR were 58.9% and 87.7%, respectively. Most toxicities were mild, and no treatment‐related deaths occurred. Grade 3 to 4 toxicities occurred in 22 patients (30.1%) as follows: leukopenia (13.7%), neutropenia (12.3%), anemia (5.5%), thrombocytopenia (1.4%), diarrhea (6.8%), vomiting (2.7%), stomatitis (1.4%), peripheral neuropathy (1.4%), and hand‐foot syndrome (1.4%). Seven patients achieved good responses and underwent gastrectomy plus metastasectomy. Thirty (41.1%) patients had S‐1 maintenance with a median of four cycles. S‐1 plus Nab‐PTX is an efficient and safe regimen as first‐line treatment for patients with AGC.

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“…In the ABSOLUTE phase III trial, nab-paclitaxel was non-inferior to paclitaxel in terms of OS (60), but due to the additional cost, the former will not replace the latter. TAS-102 is a novel oral nucleoside antitumor agent containing trifluridine and tipiracil hydrochloride, which prevents the degradation of trifluridine.…”

Section: Chemotherapymentioning

confidence: 99%

Current therapeutic landscape for advanced gastroesophageal cancers

et al. 2018

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Treatment of advanced gastroesophageal cancers remains challenging for clinicians, patients, and caregivers alike. Despite considerable research, the therapeutic armamentarium is restricted and hardly personalized. In the first-line setting, trastuzumab with a fluoropyrimidine and platinum agent is the standard-of-care in patients with HER2-positive tumor. For the others, a platinum-based doublet (preferably with oxaliplatin) is recommended. Three-drug cytotoxic regimens should be reserved for exceptional cases where patients have good performance status. Triple combinations produce higher toxicity and provide marginal advantage. In the second line setting, the combination of paclitaxel and ramucirumab is preferred over all others. Currently, nothing is approved in the 3 rd or later line. Nivolumab has resulted in an improved benefit in an Asian trial. Early trials of TAS-102, STAT3 inhibitors, anti-claudin 18.2 and other immune checkpoint inhibitors (alone or in combination) are ongoing. However, development of reproducible biomarkers for patient enrichment is critical for future progress.

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Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial

Cited by 151 publications

References 21 publications

Peritoneal metastasis as a predictive factor for nab-paclitaxel in patients with pretreated advanced gastric cancer: an exploratory analysis of the phase III ABSOLUTE trial

Peritoneal metastasis as a predictive factor for nab-paclitaxel in patients with pretreated advanced gastric cancer: an exploratory analysis of the phase III ABSOLUTE trial

Phase II clinical trial of S‐1 plus nanoparticle albumin‐bound paclitaxel in untreated patients with metastatic gastric cancer

Current therapeutic landscape for advanced gastroesophageal cancers

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