Naoki Haratake1,2, Mototsugu Shimokawa3, Takashi Seto4, Hiroshige Yoshioka5, Nobuyuki Yamamoto6, Kazuhiko Nakagawa7, Tetsuya Mitsudomi8. 1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. Department of Thoracic Oncology, National Hospital Organization, Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan. 3. Department of Biostatistics, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan. 4. Department of Thoracic Oncology, National Hospital Organization, Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan. setocruise@gmail.com. 5. Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata, Japan. 6. Internal Medicine III, Wakayama Medical University Hospital, Wakayama, Japan. 7. Department of Medical Oncology, Kindai University Hospital, Osaka-Sayama, Japan. 8. Division of Thoracic Surgery, Department of Surgery, Kindai University Hospital, Osaka-Sayama, Japan.
Abstract
BACKGROUND: Pemetrexed is common cytotoxic chemotherapy among non-squamous non-small cell lung cancer (non-Sq-NSCLC) patients; however, among epidermal growth factor receptor (EGFR)-positive lung cancer, there is no clear evidence to support the efficacy of sequential treatment with pemetrexed. MATERIAL AND METHODS: We performed a post-hoc analysis of subsequent chemotherapies among 144 patients who received the post-protocol treatment in the phase III trial WJTOG 3405 comparing gefitinib to cisplatin plus docetaxel, and analyzed the effect of pemetrexed on overall survival (OS). RESULTS: Patients with treatment including pemetrexed exhibited significantly longer OS in comparison to those without pemetrexed; the median OS in the pemetrexed + and pemetrexed- patients were 40.7 months and 28.0 months, respectively (0.55 of HR [95% CI: 0.38-0.80, p = 0.0020]). On the other hand, other treatments, including docetaxel, TS-1 and paclitaxel showed no significant impact on OS. The multivariate analysis with a time-dependent Cox proportional hazards model showed that treatment including pemetrexed, as well as PS 0 and post-operative recurrence, were independent predictors of a good prognosis. Moreover, among patients who received at least four lines of prior treatment, pemetrexed + treatment also significantly prolonged OS in comparison to pemetrexed- treatment (median OS pemetrexed + vs. pemetrexed-: 44.4 months vs. 32.6 months; HR: 0.55 [95% CI: 0.31-0.94, p = 0.0290]). CONCLUSIONS: Sequential treatment including pemetrexed against EGFR-mutated NSCLC might be associated with a better outcome. It was considered that pemetrexed should be administered without fail as a sequential treatment to improve the prognosis of EGFR-mutated NSCLC as well as like EGFR-tyrosine kinase inhibitors.
BACKGROUND: Pemetrexed is common cytotoxic chemotherapy among non-squamous non-small cell lung cancer (non-Sq-NSCLC) patients; however, among epidermal growth factor receptor (EGFR)-positive lung cancer, there is no clear evidence to support the efficacy of sequential treatment with pemetrexed. MATERIAL AND METHODS: We performed a post-hoc analysis of subsequent chemotherapies among 144 patients who received the post-protocol treatment in the phase III trial WJTOG 3405 comparing gefitinib to cisplatin plus docetaxel, and analyzed the effect of pemetrexed on overall survival (OS). RESULTS: Patients with treatment including pemetrexed exhibited significantly longer OS in comparison to those without pemetrexed; the median OS in the pemetrexed + and pemetrexed- patients were 40.7 months and 28.0 months, respectively (0.55 of HR [95% CI: 0.38-0.80, p = 0.0020]). On the other hand, other treatments, including docetaxel, TS-1 and paclitaxel showed no significant impact on OS. The multivariate analysis with a time-dependent Cox proportional hazards model showed that treatment including pemetrexed, as well as PS 0 and post-operative recurrence, were independent predictors of a good prognosis. Moreover, among patients who received at least four lines of prior treatment, pemetrexed + treatment also significantly prolonged OS in comparison to pemetrexed- treatment (median OS pemetrexed + vs. pemetrexed-: 44.4 months vs. 32.6 months; HR: 0.55 [95% CI: 0.31-0.94, p = 0.0290]). CONCLUSIONS: Sequential treatment including pemetrexed against EGFR-mutated NSCLC might be associated with a better outcome. It was considered that pemetrexed should be administered without fail as a sequential treatment to improve the prognosis of EGFR-mutated NSCLC as well as like EGFR-tyrosine kinase inhibitors.
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