No abstract

PurposeNivolumab is recommended for patients with advanced esophageal squamous cell carcinoma (aESCC) who are refractory or intolerant to fluoropyrimidine-based and platinum-based chemotherapy regardless of tumor proportion score (TPS). However, the predictive role of combined positive score (CPS) to predict nivolumab efficacy is unclear.MethodsWe retrospectively collected data from patients with aESCC, who were previously treated with fluoropyrimidines and platinum, and subsequently received nivolumab monotherapy between January 1, 2014 and September 15, 2020. Next, we examined the impact of CPS and TPS on clinical response to nivolumab. The inclusion criteria were refraction or intolerance to fluoropyrimidines and platinum, absence of comorbid malignancies, availability of tissue specimen for immunohistochemistry and programmed cell death-1 analysis results before initiating nivolumab.ResultsFifty patients were included (CPS, ≥ 10/1–10/< 1, n = 23/18/9; TPS, ≥ 10/1–10/< 1%, n = 17/8/25). The median progression-free survival were 4.1, 2.5, and 1.4 months in CPS ≥ 10, 1–10 (hazard ratio [HR] vs. CPS ≥ 10, 1.05; p = 0.90), and < 1 (HR vs. CPS ≥ 10, 3.75; p = 0.003) groups, respectively. Furthermore, among the patients with CPS ≥ 10/1–10/< 1, and TPS ≥ 10/1–10/< 1%, objective response rate were 32/25/0% and 36/0/19%. In addition, disease control rate were 63/50/11% (p = 0.04) and 65/40/38% (p = 0.30).ConclusionsThis study proposes that CPS can predict responses to nivolumab in patients with aESCC better than TPS, making it especially useful for predicting negative outcomes for those with CPS < 1.

Herein, we report a fully remote clinical trial of an oral anticancer drug, which is the first of its kind in Japan. This framework is a breakthrough that allows patients to participate in clinical trials for investigational new drugs without having to visit distant trial sites.

133 Background: Since the results of the ReDOS study were published, starting regorafenib (REG) at a reduced dose is now considered a treatment option for patients with metastatic colorectal cancer (mCRC). However, the impact of starting REG at a reduced dose on treatment outcomes in the real-world setting has not been fully investigated. Methods: We retrospectively analyzed patients who received REG for mCRC at 4 institutions between May 2013 and December 2020. These patients were divided into two groups: those who started REG before (Period A) and after (Period B) the ReDOS study publication (May 2018). The treatment outcomes between Period A and B were compared in this analysis. Results: A total of 573 patients were evaluated (385 in Period A and 188 in Period B, respectively). In Period B, significantly more patients started REG with reduced dose (34.3% vs. 75.5%, p< 0.001). The median time to first dose reduction was 32.0 days [95% CI: 29.1-34.9] in Period A and 61.0 days [95% CI: 33.7-88.9] in Period B, which was significantly longer in Period B (HR = 0.685, p= 0.003). Both any grades and ≥grade3 hand foot skin reaction (HFSR) were significantly less frequent in Period B than in Period A (any grades: 65.5% vs 54.8%, p= 0.017, ≥grade3: 21.3% vs 14.4%, p= 0.054). The median time to onset of any grades HFSR was 16.0 days [95% CI: 13.6-18.4] in Period A and 28.0 days [95% CI: 15.6-40.4] in Period B, which was significantly longer in Period B (HR = 0.738, p= 0.007). The median overall survival was 6.7 months [95% CI: 5.9-7.4] in Period A, and 5.4 month [95% CI: 4.3-6.5] in Period, respectively (HR = 1.105, p= 0.281). The median progression free survival was 2.0 months [95% CI: 1.9-2.1] in Period A and 2.1 months [95% CI: 1.8-2.4] in Period B, respectively (HR = 1.064, p= 0.498). Conclusions: Our results suggest that starting REG at a reduced dose may contribute to reducing the frequency and delaying the onset of HFSR, whereas it may not affect efficacy.

331 Background: Anamorelin is a highly selective ghrelin receptor agonist that improves appetite and increases lean body mass in patients (pts) with cachexia. We aimed to investigate the predictors of therapeutic efficacy of anamorelin in pts with gastrointestinal cancer. Methods: This retrospective study included pts with gastric cancer (GC), pancreatic cancer (PC), and colorectal cancer (CRC) treated with anamorelin at our institution between May 2021 and July 2022. Glasgow Prognostic Score (GPS) was defined as follows: GPS 0: CRP≤1.0 (mg/dL) and Alb≥3.5 (g/dL), GPS 1: either CRP>1.0 or Alb<3.5, GPS 2: CRP>1.0 and Alb<3.5. The endpoints were the response rate (RR) of anamorelin and time to treatment failure (TTF). RR was defined as the proportion of appetite improvement within 3 weeks of anamorelin, and TTF was defined as the time from the start of anamorelin to discontinuation due to insufficient response. The observation period lasted 12 weeks. RR was analyzed by univariate and multivariate logistic regression analyses, and TTF by competing risk analysis. In the competing analysis, discontinuation of anamorelin due to worse symptoms, hospital transfer for poor condition, and adverse events (AEs) were considered as competing events. Results: A total of 103 pts were included; median age was 70 (range: 37–84) years, 61 pts (59%) were men, and 17 pts (17%) had an ECOG PS ≥2. The proportion of GC/PC/CRC were 43/42/16%; median body mass index (BMI) was 19.9 (range: 14.4–26.8) kg/m2. The treatment line for 1st/2nd/≥3rd/others was 51/13/14/22%, respectively. GPS was 0/1/2 in 21/30/49%, respectively. Except for treatment line, there were no significant differences in patient characteristics according to the cancer type. A total of 12 pts discontinued treatment owing to AEs (nausea, 3; epigastric distress, 2; fatigue, 2; poor physical condition, 2; staggering, 1; pulsation, 1; diarrhea, 1 pts). The RR was 42%. Pts with GPS 2 had less improvement in appetite than those with GPS 0 or 1 (26% vs. 56%, adjusted odds ratio [95% confidence interval (95%CI)]:0.22 [0.07–0.69], p=0.009). The RR of pts with GC, PC, and CRC were 44%, 42%, and 41%, respectively. The cumulative incidence of discontinuation of anamorelin after 12 weeks was higher in pts with GPS 2 than in those with GPS 0 or 1 (46% vs. 30%). The TTF in pts with GPS 2 was significantly shorter than that in pts with a GPS 0 or 1 (adjusted subdistributional hazard ratio [95%CI]:2.80 [1.37–5.72], p=0.005). There was no statistically significant difference in TTF by cancer type, although TTF was shorter in GC and PC than in CRC. Other factors, including age, sex, baseline BMI, ECOG PS, lines of therapy, and cancer type did not correlate with RR and TTF. Conclusions: In pts with a GPS of 0 or 1, anamorelin showed better appetite improvement and a longer treatment effect than in those with GPS 2. TTF was shorter in pts with GC and PC; therefore, the timing of use should be carefully considered.