PURPOSE This study evaluated the continuous use of trastuzumab beyond progression (TBP) in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. PATIENTS AND METHODS Patients with HER2-positive advanced G/GEJ cancer refractory to first-line chemotherapy with trastuzumab in combination with fluoropyrimidine and platinum were eligible. Patients were randomly assigned to the paclitaxel (80 mg/m2, days 1, 8, and 15, every 4 weeks) or paclitaxel with trastuzumab (PT; initially 8 mg/kg followed by 6 mg/kg, every 3 weeks) arms. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate, and safety. Biomarkers such as HER2 expression status in tumor tissue after first-line treatment, HER2 amplification evaluated in serum cell-free DNA, and soluble HER2 levels were analyzed. RESULTS Overall, 91 patients were allocated to the paclitaxel (n = 46) and PT (n = 45) arms. The median PFS in the paclitaxel and PT arms was 3.2 and 3.7 months, respectively (hazard ratio [HR], 0.91; 80% CI, 0.67 to 1.22; P = .33), and the median OS in both arms was 10 months (HR, 1.2; 95% CI, 0.75 to 2.0; P = .20). The overall response rates in the paclitaxel and PT arms were 32% and 33%, respectively ( P = 1.00), and safety was comparable between the 2 arms. On exploratory analyses, HER2 positivity of tumor tissues was lost after first-line chemotherapy in 11 (69%) of 16 patients whose tumor tissues were available, and circulating HER2 DNA amplification was detected in 41 (60%) of 68 patients. However, no biomarkers associated with efficacy of TBP were found. CONCLUSION The TBP strategy failed to improve PFS in patients with HER2-positive advanced G/GEJ cancer, and no beneficial biomarkers were found.
The International Union Against Cancer (UICC) does not define the number of sections required from each regional lymph node to record pTNM classification. This study was designed to clarify the incidence of occult metastasis and to assess the pN upgrading of patients with oral cancer. Ultimately, this study led to a proposal for appropriate semiserial sectioning guidelines. Five hundred fifty-four nonmetastatic cervical lymph nodes taken from 73 patients with oral cancer were subjected to hematoxylin-eosin (HE) staining and keratin immunohistochemistry. Micrometastases, defined as foci ≤3 mm, were detected in 29 sites of 23 lymph nodes (4.2%) of 16 patients (21.9%). In 9 patients (12.3%) pN upgrading was needed: in 6 from pN0 to pN1, in 1 from pN0 to pN2b, and in 2 from pN1 to pN2b. The remaining 13 lymph nodes with occult metastasis were found in 5 pN2b and 2 pN2c patients, resulting in no pN upgrading. Occult metastasis was also detected in 6 small lymph nodes ≤5 mm in diameter. The average minor axis of the micrometastasis was 1.36±0.85 mm. We propose that the lymph nodes should be cut and examined at 1-mm intervals to detect micrometastatic foci and to evaluate the pN classification accurately.
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