Final overall survival analysis from the phase III J-ALEX study of alectinib versus crizotinib in ALK inhibitor-naïve Japanese patients with ALK-positive non-small-cell lung cancer.

BACKGROUND: Mature progression-free survival (PFS) data from the phase III J-ALEX study showed superiority for alectinib versus crizotinib [hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.26-0.52; median PFS 34.1 versus 10.2 months, respectively] in advanced ALK (anaplastic lymphoma kinase)-positive non-small-cell lung cancer (NSCLC). Overall survival (OS) data were immature (HR 0.80, 99.8799% CI 0.35-1.82) at the time of data cut-off (30 June 2018). We report final OS data after ≥5 years of follow-up. PATIENTS AND METHODS: ALK inhibitor naive Japanese patients who were chemotherapy naive or had received one prior chemotherapy regimen were enrolled. Patients were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was independent review facility-assessed PFS, with OS (not fully powered) as a secondary endpoint. RESULTS: Median duration of OS follow-up was 68.6 months with alectinib and 68.0 months with crizotinib. Treatment with alectinib did not prolong OS relative to crizotinib (HR 1.03, 95.0405% CI 0.67-1.58; P = 0.9105). Five-year OS rates were 60.9% (95% CI 51.4-70.3) with alectinib and 64.1% (95% CI 54.9-73.4) with crizotinib. In total, 91.3% (n = 95/104) of crizotinib-treated patients and 46.6% (n = 48/103) of alectinib-treated patients received at least one subsequent anticancer therapy. After study drug discontinuation, 78.8% of patients in the crizotinib arm switched to alectinib, while 10.7% of patients in the alectinib arm switched to crizotinib as a first subsequent anticancer therapy. Patients randomized to crizotinib tended to switch treatment earlier than those randomized to alectinib. CONCLUSION: Final OS analysis from J-ALEX did not show superiority of alectinib to crizotinib; this result was most likely confounded by treatment crossover. Alectinib remains a standard of care for the treatment of patients with advanced ALK-positive NSCLC.

A multicenter cohort study of osimertinib compared with afatinib as first-line treatment for EGFR-mutated non-small-cell lung cancer from practical dataset: CJLSG1903.

BACKGROUND: FLAURA, the prospective trial of osimertinib as a first-line therapy compared with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), did not show superior survival benefit for osimertinib in either the subgroup of Asians or the subgroup with the L858R mutation. In addition, the superiority of osimertinib compared with second-generation EGFR-TKI is thus far unclear. PATIENTS AND METHODS: We reviewed the clinical data of all consecutive patients who were treated with osimertinib or afatinib as first-line therapy between May 2016 and October 2019 from 15 institutions in Japan. We defined the groups based on first-line EGFR-TKI as the afatinib group and the osimertinib group. Outcomes included time to discontinuation of any EGFR-TKI (TD-TKI), overall survival (OS), and time to treatment failure, with propensity score analysis carried out as an exploratory analysis in the survival and subgroup analyses. RESULTS: A total of 554 patients were enrolled. Data on 326 patients in the osimertinib group, and 224 patients in the afatinib group were analyzed. TD-TKI adjusted by propensity score in the afatinib and osimertinib groups was 18.6 months (95% confidence interval 15.8 to 22.0) and 20.5 months (95% confidence interval 13.8 to not reached), respectively, without significant difference (P = 0.204). OS adjusted by propensity score favored the afatinib group with a significant difference (P = 0.018). Subgroup analysis with propensity score showed that patients with L858R and without brain metastasis had superior survival benefit with afatinib compared with osimertinib (P < 0.001). CONCLUSIONS: TD-TKI in the afatinib group was not significantly prolonged compared with the osimertinib group in the practical data. In the exploratory analysis of patients with L858R-mutated non-small-cell lung cancer without brain metastasis, afatinib showed more benefit in OS over osimertinib.

Gastric cancer with metastases to the distant peritoneum: a 20-year surgical experience.

BACKGROUND/AIMS: The efficacy of palliative gastrectomy in gastric cancer with peritoneal metastases remains uncertain. The aim of the present study was to evaluate the benefits of gastrectomy on the postoperative course of patients with gastric cancer and simultaneous metastases to the distant peritoneum. METHODOLOGY: A total of 122 patients who had gastric cancer and metastases to the distant peritoneum were studied with respect to survival. RESULTS: The extent of peritoneal metastases did not significantly affect the prognosis. Moreover, multivariate analysis indicated that surgery without gastrectomy was the only significant prognostic factor (relative risk, 2.587). CONCLUSIONS: Our results suggest that the decision to perform gastrectomy does not depend on the extent of peritoneal metastasis in gastric cancer. Furthermore, palliative gastrectomy, if feasible, seems to have a beneficial effect on the postoperative course and is indicated for patients regardless of metastasis to the peritoneum, if the primary tumor is surgically resectable and there is no evidence of liver metastasis.

Clinical effects of proteinase, sfericase (AI-794), on chronic bronchitis and similar diseases.

The clinical effect and utility of sfericase was compared with an inactive placebo by a double-blind method in three groups of a total 109 patients suffering from chronic respiratory diseases who had complained of difficult expectoration of sputum. A significantly greater improvement of expectoration was obtained in Group A-1 (6 tablets/day). Also in group A-1, more cases showed subjective and objective improvement, i.e., improvement in expectoration, reduction in coughs, decrease in the amount of sputum, and disappearance of râles. However, the sputum and its degree of purulency remained unchanged in most cases in all three groups. Side effects were few. The clinical efficacy of sfericase in the group with 2 tablets, 3X/day (total daily dose of 6 tablets) was shown to be significantly superior to the other two groups. This dosage was established as the optimal dose for treating difficulty in expectoration.

[Clinical studies of cefoxitin for the treatment of respiratory tract infections (author's transl)].

A total of 42 patients who were suffering from respiratory tract infections were treated with cefoxitin, and the following results were obtained. 1. Out of 32 patients clinically evaluated, excellent or good responses were observed in 30 patients (94%). 2. Presumed causative organisms were isolated in 14 patients. The organisms were eradicated in 11 patients and the eradication rate was 79% (11/14). The number of the organisms decreased or unchanged in 1 patient each. In other 1 patient the pathogenic agent was replaced with other agents during the course of treatment. 3. As for the side effects, skin eruption was observed in 3 patients. One patient received drugs other than cefoxitin concomitantly that might have caused the eruption. Another patient had an allergic history to many antibiotics. In 4 patients slight elevations of S-GOT and S-GPT were observed but improved soon after the completion of cefoxitin treatment. In 1 patient an elevation of serum creatinine was observed but this was not attributed to the administration of cefoxitin. 4. From the results stated above, cefoxitin is considered to be a safe and effective antibiotic which can be one of the first-choice antibiotics for the treatment of respiratory tract infections.