Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial.

BACKGROUND: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented. PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population. RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage). CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.

Long-term Survival Outcomes of 'Low Risk' Ductal Carcinoma in situ from a Territory-wide Cancer Registry.

AIMS: The LORIS trial is an ongoing phase III clinical trial on low risk ductal carcinoma in situ (DCIS). DCIS patients aged ≥46 years with screen-detected low/intermediate nuclear grade were considered low risk and were randomised into surveillance or standard surgery. Here we review the 10-year territory-wide breast cancer registry database and evaluate the clinical outcomes of low versus high risk DCIS patients. MATERIALS AND METHODS: This was a retrospective study of a prospectively maintained territory-wide breast cancer registry in Hong Kong. RESULTS: Between 1997 and 2006, 1391 DCIS patients were identified from the Hong Kong cancer registry breast cancer database. The mean age at diagnosis was 49.2 years (range 30-70). In total, 372 patients were classified as 'low risk', whereas the remaining 777 patients were classified as 'high risk'. After a median follow-up of 11.6 years, the 10-year overall breast cancer-specific survival of the entire DCIS cohort was 1136/1149 (98.9%). Overall breast cancer-specific survival of low risk DCIS was 99.5%, whereas that in high risk DCIS was 98.6% (Log-rank test, P = 0.208). Forty-six (12.4%) patients in the LORIS low risk group did not receive surgery, whereas 93 (12%) patients in the LORIS high risk group did not receive surgery. The 10-year breast cancer-specific survival in the non-operated low risk DCIS group was 97.8%; that in the non-operated high risk DCIS group was 96.7% (P = 1). CONCLUSION: Long-term survival of DCIS was excellent, especially in low risk DCIS, regardless of surgical treatment.

Clinical outcomes of patients with ductal carcinoma in situ in Hong Kong: 10-year territory-wide cancer registry study.

BACKGROUND: Incidence of ductal carcinoma in situ (DCIS) has increased in recent decades because of breast cancer screening. This study comprised a long-term survival analysis of DCIS using 10-year territory-wide data from the Hong Kong Cancer Registry. METHODS: This study included all patients diagnosed with DCIS in Hong Kong from 1997 to 2006. Exclusion criteria were age <30 years or ≥70 years, lobular carcinoma in situ, Paget's disease, and co-existing invasive carcinoma. Patients were stratified into those diagnosed from 1997 to 2001 and those diagnosed from 2002 to 2006. The 5- and 10-year breast cancer-specific survival rates were evaluated; standardised mortality ratios were calculated. RESULTS: Among the 1391 patients in this study, 449 were diagnosed from 1997 to 2001, and 942 were diagnosed from 2002 to 2006. The mean age at diagnosis was 49.2±9.2 years. Overall, 51.2% of patients underwent mastectomy and 29.5% received adjuvant radiotherapy. The median follow-up interval was 11.6 years; overall breast cancer-specific mortality rates were 0.3% and 0.9% after 5 and 10 years of follow-up, respectively. In total, 109 patients (7.8%) developed invasive breast cancer after a considerable delay. Invasive breast cancer rates were comparable between patients diagnosed from 1997 to 2001 (n=37, 8.2%) and those diagnosed from 2002 to 2006 (n=72, 7.6%). CONCLUSION: Despite excellent long-term survival among patients with DCIS, these patients were more likely to die of breast cancer, compared with the general population of women in Hong Kong.

Prognostic factors associated with clear cell sarcoma in 14 Chinese patients.

PURPOSE. To identify prognostic factors associated with clear cell sarcomas in 14 Chinese patients. METHODS. Medical records of 7 men and 7 women (mean age, 36 years) with histologically confirmed clear cell sarcoma of tendons and aponeuroses were reviewed. Patient demographics, tumour characteristics, and treatment modalities were retrieved. Prognostic factors associated with favourable 5-year survival were determined. RESULTS. The most affected sites were the thigh (n=5) and the foot (n=4); the mean time from symptom onset to diagnosis was 9.5 months. The tumour stage at diagnosis was IIA in 8 patients, IIB in 2, and III in 4. The mean tumour size was 4.5 cm in diameter. One patient was lost to follow-up. For the remaining 13 patients, the mean time to disease-related mortality was 2.5 years. Nine patients had distant metastases; the most common sites were lungs and pleura (n=7), followed by distant lymph nodes (n=4), bone (n=2), pericardium (n=2), and brain (n=1). All patients underwent surgical excision. Three women and one man (mean age, 27 years) attained 5-year disease-free survival. All had stage IIA tumours at diagnosis. Their mean tumour size was 1.75 cm in diameter, which was significantly smaller than that of all patients (4.5 cm). Tumour size of ≤ 2.5 cm in diameter (p=0.004) and stage IIA tumour at diagnosis (p=0.04) were significant prognostic factors for 5-year survival. CONCLUSION. Tumour size of ≤ 2.5 cm and early stage tumour are associated with 5-year disease-free survival. Early detection is crucial for the prognosis of clear cell sarcomas.

Curative radiotherapy for early cancers of the lip, buccal mucosa, and nose--a simple interstitial brachytherapy technique employing angiocatheters as carriers for Iridium-192 wire implants.

OBJECTIVES: To evaluate treatment outcomes following interstitial brachytherapy for cancers of the lip, buccal mucosa, or nose. DESIGN: Retrospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: A cohort of 13 patients treated uniformly by a simple interstitial brachytherapy technique employing plastic angiocatheters as carriers for Iridium-192 wires: all but one patient had T1 or T2 tumours and all but one had N0 disease. MAIN OUTCOME MEASURES: Local and loco-regional control rates. RESULTS: Six of the 13 patients received external radiotherapy prior to interstitial brachytherapy. A median brachytherapy dose of 70 Gy was delivered to those treated with brachytherapy alone, while 35 Gy was delivered after a median external radiotherapy dose of 50 Gy to those receiving combined treatment. The 3-year actuarial local control rate was 75%. No significant late complications were observed. CONCLUSIONS: Employing a simple brachytherapy technique using angiocatheters and Iridium-192 wires, in conjunction with external radiotherapy when appropriate, produces good outcomes for patients with early lip, nasal vestibule, and buccal mucosa cancers.

Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study.

BACKGROUND: To evaluate the efficacy and toxicity of combination gemcitabine plus cisplatin (GC) chemotherapy in metastatic or recurrent nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Forty-four patients of Chinese ethnicity with metastatic or recurrent NPC received ambulatory GC chemotherapy every 28 days (gemcitabine 1000 mg/m(2) days 1, 8 and 15; cisplatin 50 mg/m(2) days 1 and 8). There were 40 male and four female patients with a mean age of 47.4 years. More than half (54.5%) of the patients had received either prior platinum-based chemotherapy and/or radiotherapy to target lesions. RESULTS: There were nine complete responses and 23 partial responses in the 44 patients, achieving an overall response rate of 73% (78% for the 41 assessable patients). The mean duration of response was 5.3 months. Improved subjective symptom-control scores were found in 78% of patients with pre-existing symptoms, while 64% of patients experienced improved general well-being scores. Toxicity was mainly hematological: grade III/IV anemia, granulocytopenia and thrombocytopenia were found in 11, 37 and 16% of cycles, respectively. With a median follow-up of 17.2 months, 62% survived 1 year while 36% were alive and progression free. CONCLUSIONS: Gemcitabine plus cisplatin chemotherapy offers a satisfactory overall response rate, subjective patient improvement and safety profile for metastatic and recurrent NPC.