Background Regimens for palliation in patients with head and neck cancer recommended by the US National Comprehensive Cancer Network (NCCN) have low applicability (less than 1-3%) in low-income and middle-income countries (LMICs) because of their cost. In a previous phase 2 study, patients with head and neck cancer who received metronomic chemotherapy had better outcomes when compared with those who received intravenous cisplatin, which is commonly used as the standard of care in LMICs. We aimed to do a phase 3 study to substantiate these findings. MethodsWe did an open-label, parallel-group, non-inferiority, randomised, phase 3 trial at the Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India. We enrolled adult patients (aged 18-70 years) who planned to receive palliative systemic treatment for relapsed, recurrent, or newly diagnosed squamous cell carcinoma of the head and neck, and who had an Eastern Cooperative Oncology Group performance status score of 0-1 and measurable disease, as defined by the Response Evaluation Criteria In Solid Tumors. We randomly assigned (1:1) participants to receive either oral metronomic chemotherapy, consisting of 15 mg/m² methotrexate once per week plus 200 mg celecoxib twice per day until disease progression or until the development of intolerable side-effects, or 75 mg/m² intravenous cisplatin once every 3 weeks for six cycles. Randomisation was done by use of a computer-generated randomisation sequence, with a block size of four, and patients were stratified by primary tumour site and previous cancer-directed treatment. The primary endpoint was median overall survival. Assuming that 6-month overall survival in the intravenous cisplatin group would be 40%, a non-inferiority margin of 13% was defined. Both intention-to-treat and per-protocol analyses were done. All patients who completed at least one cycle of the assigned treatment were included in the safety analysis. This trial is registered with the Clinical Trials Registry-India, CTRI/2015/11/006388, and is completed. Findings Between May 16, 2016, and Jan 17, 2020, 422 patients were randomly assigned: 213 to the oral metronomic chemotherapy group and 209 to the intravenous cisplatin group. All 422 patients were included in the intention-totreat analysis, and 418 patients (211 in the oral metronomic chemotherapy group and 207 in the intravenous cisplatin group) were included in the per-protocol analysis. At a median follow-up of 15•73 months, median overall survival in the intention-to-treat analysis population was 7•5 months (IQR 4•6-12•6) in the oral metronomic chemotherapy group compared with 6•1 months (3•2-9•6) in the intravenous cisplatin group (unadjusted HR for death 0•773 [95% CI 0•615-0•97, p=0•026]). In the per-protocol analysis population, median overall survival was 7•5 months (4•7-12•8) in the oral metronomic chemotherapy group and 6•1 months (3•4-9•6) in the intravenous cisplatin group (unadjusted HR for death 0•775 [95% CI 0•616-0•974, p=0•029]). Grade 3 or highe...

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Background Prolonged infusion of low dose gemcitabine (PLDG) in combination with platinum has shown promising activity in terms of improved response rate and progression free survival (PFS); especially in squamous non-small cell lung cancer (NSCLC). Hence, we conducted a phase 3 randomized non-inferiority study with the primary objective of comparing the overall survival (OS) between PLDG and standard dose of gemcitabine with platinum. Methodology Adult subjects (age ≥ 18 years), with stages IIIB–IV, NSCLC (squamous) and ECOG performance status of ≤ 2 were randomized 1:1 into either carboplatin with standard dose gemcitabine (1000 mg/m 2 intravenous over 30 min, days 1 and 8) (STD-G arm) or carboplatin along with low dose gemcitabine (250 mg/m 2 intravenous over 6 h, days 1 and 8) (LOW-G arm) for a maximum of 6 cycles. Tumor response was assessed by RECIST criteria version 1.1 every 2 cycles till 6th cycle and thereafter at 2 monthly intervals till progression. The primary endpoint was overall survival. 308 patients were randomized, 155 in STD-G arm and 153 in LOW-G arm, respectively. Results The median overall survival in STD-G arm was 6.8 months (95%CI 5.3–8.5) versus 8.4 months (95%CI 7–10.3) in the LOW-G arm (HR-0.890 (90%CI 0.725–1.092). The results with per protocol analysis were in line with these results. There was no statistical difference in progression free survival (HR-0.949; 90%CI 0.867–1.280) and adverse event rate between the 2 arms. Conclusion This study suggests that PLDG is an alternative to the standard gemcitabine schedule in squamous NSCLC, and either of these can be selected subject to patient convenience.

Introduction The prognosis of anaplastic lymphoma kinase (ALK) fusion-positive metastatic non-small cell lung cancer (mNSCLC) patients has improved drastically since the introduction of targeted therapies. Apart from age, performance status, and type of driver mutation in a mNSCLC, prognosis also depends on baseline metastatic sites number as well as location with liver metastases being a poor prognostic factor. However, the clinical and prognostic association of baseline liver metastases in ALK fusion-positive mNSCLC is not well known. Material and Methods We performed a retrospective analysis of ALK fusion-positive mNSCLC patients to assess prognostic impact of liver metastases. Records were obtained from lung cancer audit database and electronic medical records. Patients were started on either chemotherapy, ALK-directed tyrosine kinase inhibitors, or given best supportive care as per the clinical scenario. Radiological response was assessed every 2 to 3 months or earlier at clinical suspicion of progressive disease. Adverse events were evaluated as per Common Terminology Criteria for Adverse Events v4.02. Results A total of 441 patients were screened, out of which 76 had baseline liver metastases. Median age was 49 years with 64.5% males. Median progression-free survival (mPFS) was 14.2 months (95% confidence interval [CI] 8.9–19.4) in patients with baseline liver metastases. In patients who received first-line ALK inhibitor therapy versus who received first-line chemotherapy, mPFS was significantly better in the ALK-directed therapy subgroup, 15.3 months (95% CI 11.7–18.9) versus 5.9 months (95% CI 2.7–9.1), respectively (hazard ratio [HR] 0.3 [95% CI 0.17–0.54]; p < 0.001). Median overall survival (mOS) was 27.6 months (95% CI 17.4–37.7) in patients with baseline liver metastases which was not statistically significant from patients without baseline liver metastases which was 32.3 months (95% CI 28.8–35.7) (HR 1.32 [95% CI 0.91–1.9]; p = 0.22). Use of ALK-directed therapy in patients with baseline liver metastases resulted in better OS, mOS not reached versus 15.7 months (95% CI 2.7–28.8) in the chemotherapy group (HR 0.33 [95% CI 0.16—0.67]; p < 0.001). Conclusion In patients with ALK fusion-positive mNSCLC, baseline liver metastases was not found to be an independent prognostic factor. However, the use of ALK-directed therapy resulted in a significantly better PFS and OS as compared with chemotherapy in patients with baseline liver metastases. This underscores the importance of the use of ALK-directed therapy whenever feasible in this group of patients.