Bleeding negatively impacts quality of life in patients with unresectable advanced gastric cancer and has the potential to be lethal. When blood transfusion and endoscopic hemostasis are unsuccessful to stop bleeding, radiation to stomach is selected in patients with unsuitable condition for surgery. We performed a retrospective cohort study to clarify the utility of radiotherapy in treating gastric bleeding, particularly for patients with limited life expectancy. We evaluated the efficacy and safety of palliative radiotherapy in patients with advanced gastric cancer between January 2007 and December 2012 in Aichi Cancer Center Hospital. All patients had gastric bleeding requiring blood transfusion. We defined hemostasis as an increase in hemoglobin level to more than 7.0 g/dL together with the cessation of melena or hematemesis for at least 1 week. During the study period, 313 advanced gastric cancer patients treated in our institution. Of these 17 patients received gastric radiotherapy to stop bleeding. Two patients were excluded from analysis due to combined treatment of intravascular embolization. Eleven out of 15 patients (73 %) had undergone two or more previous chemotherapy regimens. Ten patients (67 %) had an Eastern Cooperative Oncology Group performance status of 3 and 14 patients (93 %) were in palliative prognostic index group B or C. The median total planned radiation dose was 30 Gy in 10 fractions. At a median interval of 2 days after initiation of radiotherapy, 11 patients (73 %) achieved hemostasis; rebleeding was observed in four patients (36 %). The median hemoglobin level before radiotherapy was significantly increased from 6.0 to 9.0 g/dL (p < 0.0001). The median volume of red blood cell transfusion was significantly decreased from 1120 to 280 mL (p = 0.007). The median rebleeding-free survival interval was 27 days, with a median overall survival of 63 days. The cause of death was bleeding in 1 patient (7 %) and cancer progression without bleeding in 12 patients (80 %). There were no severe adverse events attributable to radiotherapy. Palliative radiotherapy for gastric bleeding achieves hemostasis within a short time frame. This appears to be a useful treatment option, especially for patients with end-stage, unresectable advanced gastric cancer.

Background/Objectives: BRAF mutations occur in 5–10% of metastatic colorectal cancer (mCRC) cases, but their implications for prognosis and optimal treatment remain unclear. Methods: This multicenter, prospective observational study analyzed 377 RAS wild-type cases from 511 patients across 32 centers, using PCR-based methods. Results: BRAF mutations were identified in 21% (79/377) of cases, predominantly V600E (89.9%) with a minority of non-V600E (10.1%). Microsatellite instability (MSI) testing revealed MSI-high in 11.3%, exclusively among V600E cases. V600E mutations were linked to right-sided tumors, poor differentiation, and elevated CA19-9 levels. Median survival was significantly lower in V600E cases compared to BRAF wild-type (12.4 vs. 37.5 months, HR 3.25, p < 0.001) and marginally lower non-V600E cases (12.4 vs. 34.7 months, HR 0.61, p = 0.057). Chemotherapy regimens (doublet vs. triplet) and targeted treatments (bevacizumab vs. anti-EGFR) showed no significant survival differences in V600E patients. Similarly, RAS/BRAF wild-type patients had comparable survival with bevacizumab versus anti-EGFR, even for left-sided tumors. Conclusions: These findings highlight distinct clinical and prognostic profiles for BRAF V600E and non-V600E mutations, while treatment choice appears to have limited impact on survival in these subgroups or RAS/BRAF wild-type cases.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are the standard treatment for advanced hormone receptor-positive breast cancer. Although interstitial lung disease is a rare (1–3.3%) but serious adverse event associated with CDK4/6 inhibitors, the incidence of interstitial lung disease in Japanese patients in the real world and the risk factors of interstitial lung disease are not clear. We retrospectively investigated the incidence of interstitial lung disease in 224 patients with advanced breast cancer who received CDK4/6 inhibitors at our hospital between 31 January 2017 and 31 January 2021. The correlation of age (>50 vs ≤50 years), presence or absence of previous history of interstitial lung disease, lung metastasis, smoking history and chest radiation with the development of interstitial lung disease was evaluated. In total, 177 cases received palbociclib, 39 cases received abemaciclib and 8 cases received both palbociclib and abemaciclib, constituting a palbociclib group (n = 185) and an abemaciclib group (n = 47). At a median observation period of 607 days, 8.0% (18/224) cases (13 definite and 5 probable cases) had interstitial lung disease; 6.5% (12/185) of palbociclib-treated and 13% (6/47) of abemaciclib-treated cases. The median time to interstitial lung disease onset was 178 (range, 14–750) days. There was no significant correlation between the background factors studied and the development of interstitial lung disease. The frequency of CDK4/6 inhibitor-induced interstitial lung disease was higher than that reported in clinical trials. We did not identify any risk factors for the development of interstitial lung disease in this study, and thus, larger studies that include patient predisposition are required.

Background: The phase 3 open-label KEYNOTE-426 study demonstrated that first-line pembrolizumab plus axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC) in a global population. This subgroup analysis investigated the efficacy and safety of pembrolizumab-axitinib versus sunitinib in patients enrolled in KEYNOTE-426 in East Asia (Japan, South Korea, and Taiwan). Methods: Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks with oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off). Dual primary endpoints were OS and PFS, assessed by blinded independent central review. Secondary endpoints were objective response rate (ORR) and safety. Results: The East Asian subgroup comprised 130 patients (pembrolizumab-axitinib, n = 62; sunitinib, n = 68; 15.1% of the global intention-to-treat population). Compared with sunitinib, pembrolizumab-axitinib OS hazard ratio (HR) was 0.85 [95% confidence interval (CI) 0.50–1.44; 36-month rates, 62.9% and 58.8%, respectively] and PFS HR was 0.59 (95% CI 0.38–0.92) in favor of pembrolizumab-axitinib. ORR favored pembrolizumab-axitinib (64.5% vs 44.1% for sunitinib). The results were generally consistent with the intention-to-treat population. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 69.4% of patients on pembrolizumab-axitinib and 74.6% on sunitinib; 16 (25.8%) patients on pembrolizumab-axitinib and 17 (25.4%) patients on sunitinib discontinued due to adverse events. No deaths from TRAEs occurred. Conclusion: Pembrolizumab-axitinib improved efficacy for East Asian patients with untreated clear cell mRCC, consistent with results from the global population. Safety was manageable. ClinicalTrials.gov identifier: NCT02853331.

In the CARMENA (Cancer du Rein Metastatique Nephrectomie et Antiangiogéniques) trial, Méjean et al. (Aug. 2 issue)¹ determine the noninferiority of sunitinib alone, as compared with nephrectomy followed by sunitinib, on the basis of the observation that the 95% confidence interval for the hazard ratio of death did not exceed 1.20 (the noninferiority margin for the trial). This conclusion was derived from the second interim analysis, in which a criterion for statistical significance was defined according to the O’Brien–Fleming boundary; this boundary was not met, but the trial was terminated early because of slow enrollment. The confidence limits of the confidence interval should have accordingly corresponded to the O’Brien–Fleming boundary, instead of the usual 95% confidence interval, and the resulting confidence interval did exceed 1.20. It is sometimes necessary to end clinical trials at an interim analysis regardless of whether they have satisfied a rigorous statistical criterion, and we believe that this is the case with the CARMENA trial. It is therefore important to clarify whether the result at the interim analysis was significant at a type I error with adjustment for multiple comparisons or was premature but sufficient to meet the objectives of the trial.