Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer: a multicenter, randomized, open-label Phase II study

K Govind Babu, Kumar Prabhash, Ashok K Vaid, Bhawna Sirohi, Ravi B Diwakar, Raghunadha Rao, Madhuchanda Kar, Hemant Malhotra, Shona Nag, Chanchal Goswami, Vinod Raina, Ravi Mohan, K Govind Babu, Kumar Prabhash, Ashok K Vaid, Bhawna Sirohi, Ravi B Diwakar, Raghunadha Rao, Madhuchanda Kar, Hemant Malhotra, Shona Nag, Chanchal Goswami, Vinod Raina, Ravi Mohan

Abstract

Background: The purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin) versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer.

Methods: This multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group) or chemotherapy alone (control group), and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m(2) and carboplatin (area under the curve 5 mg/mL*min) every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response). Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan-Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data.

Results: The objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04). A complete response and partial response were achieved in 3.6% and 50% of patients, respectively, in the nimotuzumab group, and in 4% and 30.9% of patients, respectively, in the control group. No significant differences in median progression-free survival and overall survival were observed. Safety profiles were comparable between the two groups.

Conclusion: Nimotuzumab plus chemotherapy significantly improved the objective response rate as compared with chemotherapy alone. The combination was safe and well tolerated in patients with stage IIIB/IV non-small-cell lung cancer.

Keywords: carboplatin; docetaxel; epidermal growth factor receptor; nimotuzumab; non-small cell lung cancer.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Patient disposition.
Figure 3
Figure 3
ORRs of the (A) intent-to-treat and (B) efficacy-evaluable populations. Notes: Patients with non-small-cell lung cancer were treated with nimotuzumab plus chemotherapy (nimotuzumab) or chemotherapy alone (control). The ORR was measured during tumor evaluation visits and is the sum of the CR and PR. Abbreviations: CR, complete response; PR, partial response; ORR, objective response rate.
Figure 4
Figure 4
(A) Overall survival and (B) progression-free survival in the intent-to-treat population. Notes: Overall survival and progression-free survival were estimated during the median follow-up period of 26.17 months. The Kaplan–Meier method was used to estimate median overall survival and progression-free survival of patients with non-small-cell lung cancer in the nimotuzumab (blue) or control (red) groups. The survival distribution of the two treatment groups was compared using a log-rank test.

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