There is ongoing debate regarding the significance of complete or near-complete response after neoadjuvant chemoradiotherapy (CRT) for rectal cancer. This study assessed the prognostic value of the Dworak tumor regression grade (TRG) following neoadjuvant CRT and surgery primarily in patients with pathological stage (ypStage) II and III rectal cancer. The records of 331 patients who underwent neoadjuvant CRT followed by total mesorectal excision between 2004 and 2015 were retrospectively reviewed. Patients were categorized as having a good response (GR, TRG 3/4, n = 122) or a poor response (PR, TRG 1/2, n = 209). At a median follow-up of 65 months, five-year disease-free survival (DFS) was higher in the GR group than in the PR group (91.3% vs. 66.6%, p < 0.001). Patients with a GR and ypStage II disease had a five-year DFS that was indistinguishable from that of patients with ypStage 0–I disease (92.3% vs. 90.7%, p = 0.885). Likewise, patients with a GR and ypStage III disease had a five-year DFS similar to those with ypStage II disease (76.0% vs. 75.9%, p = 0.789). A new modified staging system that incorporates grouped TRG (GR vs. PR) was developed. The prognostic performance of this modified stage and the ypStage was compared with the Harrell C statistic. C statistic of the modified stage was higher than that of the ypStage (0.784 vs. 0.757, p = 0.012). The results remained robust after multivariate Cox regression analyses. In conclusion, a GR to neoadjuvant CRT is an independent predictor of good DFS and overall survival and further stratifies patients so as to estimate the risk of recurrence and survival among patients with ypStage II and III rectal cancer.

Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Patients were randomized 1 : 1 to DHP107 (200 mg/m² orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m² day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7–4.0) months for DHP107 and 2.6 (95% CI 1.8–2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64–1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70–1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 − 11.5) months for DHP107 versus 8.9 (95% CI 7.1–12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76–1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. NCT01839773.

Background and Aims: Biliary tract cancers are rare, heterogeneous cancers with poor prognoses. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β “trap”) fused to a human IgG1 monoclonal antibody blocking programmed death ligand 1, was evaluated in patients with locally advanced/metastatic chemorefractory biliary tract cancers. Approach and Results: This multicenter, single-arm, open-label, phase 2 study (NCT03833661) enrolled adults with locally advanced or metastatic biliary tract cancer that was intolerant to or had failed first-line systemic platinum-based chemotherapy. Patients received 1200 mg bintrafusp alfa intravenously Q2W. The primary endpoint was confirmed objective response according to Response Evaluation Criteria in Solid Tumors 1.1 assessed by IRC. Secondary endpoints included duration of response, durable response rate, safety, progression-free survival, and overall survival. Between March 2019 and January 2020, 159 patients were enrolled. Median follow-up was 16.1 (range, 0.0–19.3) months; 17 patients (10.7%; 95% CI: 6.4%–16.6%) achieved an objective response. Median duration of response was 10.0 (range, 1.9–15.7) months; 10 patients (6.3%; 95% CI: 3.1%–11.3%) had a durable response (≥6 mo). Median progression-free survival was 1.8 months (95% CI: 1.7–1.8 mo); median overall survival was 7.6 months (95% CI: 5.8–9.7 mo). Overall survival rates were 57.9% (6 mo) and 38.8% (12 mo). Grade ≥3 adverse events occurred in 26.4% of patients, including one treatment-related death (hepatic failure). Frequent grade ≥3 adverse events included anemia (3.8%), pruritus (1.9%), and increased alanine aminotransferase (1.9%). Conclusions: Although this study did not meet its prespecified primary endpoint, bintrafusp alfa demonstrated clinical activity as second-line treatment in this hard-to-treat cancer, with durable responses and a manageable safety profile.

Lee JO, et al. J Korean Med Sci. 2014 Feb;29(2):224-229. http://dx.doi.org/10.3346/jkms.2014.29.2.224