Phase III Non-inferiority Study Evaluating Efficacy and Safety of Low Dose Gemcitabine Compared to Standard Dose Gemcitabine With Platinum in Advanced Squamous Lung Cancer

Vijay Patil; Vanita Noronha; Amit Joshi; Anuradha Chougule; Sadhana Kannan; Atanu Bhattacharjee; Supriya Goud; Sucheta More; Arun Chandrasekharan; Nandini Menon; Sujay Srinivas; Dilip Harindran Vallathol; Hollis Dsouza; Swaratika Majumdar; Sudeep Das; Abhinav Zawar; Satvik Khaddar; Amit Kumar; Gunjesh Singh; Kanteti Aditya Pavan Kumar; Rahul Ravind; Vaishakhi Trivedi; Vichitra Behel; Abhishek Mahajan; Amit Janu; Nilendu Purandare; Kumar Prabhash

doi:10.1016/j.eclinm.2019.03.011

Phase III Non-inferiority Study Evaluating Efficacy and Safety of Low Dose Gemcitabine Compared to Standard Dose Gemcitabine With Platinum in Advanced Squamous Lung Cancer

EClinicalMedicine. 2019 Apr 9:9:19-25. doi: 10.1016/j.eclinm.2019.03.011. eCollection 2019 Mar.

Authors

Vijay Patil^{1

2}, Vanita Noronha^{1

2}, Amit Joshi^{1

2}, Anuradha Chougule^{1

2}, Sadhana Kannan^{3

2}, Atanu Bhattacharjee^{3

2}, Supriya Goud^{1

2}, Sucheta More^{1

2}, Arun Chandrasekharan^{1

2}, Nandini Menon^{1

2}, Sujay Srinivas^{1

2}, Dilip Harindran Vallathol^{1

2}, Hollis Dsouza^{1

2}, Swaratika Majumdar^{1

2}, Sudeep Das^{1

2}, Abhinav Zawar^{1

2}, Satvik Khaddar^{1

2}, Amit Kumar^{1

2}, Gunjesh Singh^{1

2}, Kanteti Aditya Pavan Kumar^{1

2}, Rahul Ravind^{1

2}, Vaishakhi Trivedi^{1

2}, Vichitra Behel^{1

2}, Abhishek Mahajan^{4

2}, Amit Janu^{4

2}, Nilendu Purandare^{5

2}, Kumar Prabhash^{1

2}

Affiliations

¹ Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.
² Homi Bhabha National Institute, Mumbai, India.
³ Department of Cancer Epidemiology and Biostatistics, Tata Memorial Hospital, Mumbai, India.
⁴ Department of Radiology, Tata Memorial Hospital, Mumbai, India.
⁵ Department of Nuclear Medicine, Tata Memorial Hospital, Mumbai, India.

Abstract

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/m² intravenous over 30 min, days 1 and 8) (STD-G arm) or carboplatin along with low dose gemcitabine (250 mg/m² 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.

Keywords: Gemcitabine; Low dose; NSCLC; Prolonged infusion; Squamous cell cancer.