Gefitinib

A phase III, multicenter, randomized trial compared gefitinib with carboplatin plus paclitaxel as first-line treatment in clinically selected patients in East Asia who had advanced adenocarcinoma of the lung and had never smoked or were former light smokers.[54]

A phase III, multicenter, randomized trial compared gefitinib with carboplatin plus paclitaxel as first-line treatment in clinically selected patients in East Asia who had advanced adenocarcinoma of the lung and had never smoked or were former light smokers.[54]

The study met its primary objective of demonstrating the superiority of gefitinib compared with the carboplatin-paclitaxel combination for PFS (HRprogression or death, 0.74; 95% CI, 0.65–0.85; P < .001).

A phase III, multicenter, randomized trial compared gefitinib with carboplatin plus paclitaxel as first-line treatment in clinically selected patients in East Asia who had advanced adenocarcinoma of the lung and had never smoked or were former light smokers.[54]

The median PFS was 5.7 months in the gefitinib group and 5.8 months in the carboplatin-paclitaxel group.[54][Level of evidence B1]

A phase III, multicenter, randomized trial compared gefitinib with carboplatin plus paclitaxel as first-line treatment in clinically selected patients in East Asia who had advanced adenocarcinoma of the lung and had never smoked or were former light smokers.[54]

Following the time that chemotherapy was discontinued and while gefitinib was continued, the PFS curves clearly separated and favored gefitinib.

A phase III, multicenter, randomized trial compared gefitinib with carboplatin plus paclitaxel as first-line treatment in clinically selected patients in East Asia who had advanced adenocarcinoma of the lung and had never smoked or were former light smokers.[54]

The 12-month PFS rates were 24.9% with the gefitinib group and 6.7% with the carboplatin-paclitaxel group.

A phase III, multicenter, randomized trial compared gefitinib with carboplatin plus paclitaxel as first-line treatment in clinically selected patients in East Asia who had advanced adenocarcinoma of the lung and had never smoked or were former light smokers.[54]

More than 90% of the patients in the trial with variants had either EGFR del19 or L858R variants, which have been shown to be sensitive to EGFR inhibitors. In the subgroup of patients with these variants, PFS was significantly longer among those who received gefitinib (HR, 0.48; 95% CI, 0.36–0.64; P < .001); however, in the subgroup of patients who were negative for EGFR variants, PFS was significantly longer in those who received the carboplatin-paclitaxel combination (HR with gefitinib, 2.85; 95% CI, 2.05–3.98; P < .001). There was a significant interaction between treatment and EGFR variants with respect to PFS (P < .001).[54]

A phase III, multicenter, randomized trial compared gefitinib with carboplatin plus paclitaxel as first-line treatment in clinically selected patients in East Asia who had advanced adenocarcinoma of the lung and had never smoked or were former light smokers.[54]

OS was similar for patients who received gefitinib and carboplatin-paclitaxel, with no significant difference in treatments (HR, 0.90; 95% CI, 0.79–1.02; P = .109) or in EGFR variant–positive (HR, 1.00; 95% CI, 0.76–1.33; P = .990) or EGFR variant–negative (HR, 1.18; 95% CI, 0.86–1.63; P = .309; treatment by EGFR variant interaction P = .480) subgroups. A high proportion (64.3%) of EGFR variant–positive patients randomly assigned to the carboplatin-paclitaxel regimen received subsequent EGFR TKIs. PFS was significantly longer with gefitinib for patients who had both high EGFR gene copy number and EGFR variants (HR, 0.48; 95% CI, 0.34–0.67) but significantly shorter when high EGFR gene copy number was not accompanied by an EGFR variant (HR, 3.85; 95% CI, 2.09–7.09).

A phase III trial from Japan prospectively confirmed that patients with NSCLC and EGFR variants have improved PFS but not OS when treated with gefitinib. The trial included 230 chemotherapy-naïve patients with metastatic NSCLC and EGFR variants who were randomly assigned to receive gefitinib or carboplatin-paclitaxel.[55]

A phase III trial from Japan prospectively confirmed that patients with NSCLC and EGFR variants have improved PFS but not OS when treated with gefitinib. The trial included 230 chemotherapy-naïve patients with metastatic NSCLC and EGFR variants who were randomly assigned to receive gefitinib or carboplatin-paclitaxel.[55]

In the planned interim analysis of data for the first 200 patients, PFS was significantly longer in the gefitinib group than in the standard-chemotherapy group (HRdeath or disease progression with gefitinib, 0.36; P < .001), resulting in early termination of the study.

A phase III trial from Japan prospectively confirmed that patients with NSCLC and EGFR variants have improved PFS but not OS when treated with gefitinib. The trial included 230 chemotherapy-naïve patients with metastatic NSCLC and EGFR variants who were randomly assigned to receive gefitinib or carboplatin-paclitaxel.[55]

The gefitinib group had a significantly longer median PFS (10.8 months vs. 5.4 months in the chemotherapy group; HR, 0.30; 95% CI, 0.22–0.41; P < .001).[55][Level of evidence B1] The median OS was 30.5 months in the gefitinib group and 23.6 months in the standard chemotherapy group (P = .31).

Another phase III trial from Japan also prospectively confirmed that patients with NSCLC and EGFR variants have improved PFS but not OS when treated with gefitinib. In the second trial, the West Japanese Oncology Group conducted a phase III study (WJTOG3405) in 177 chemotherapy-naïve patients aged 75 years or younger and diagnosed with stage IIIB/IV NSCLC or postoperative recurrence and EGFR variants (either the EGFR exon 19 deletion or EGFR L858R single nucleotide variant). Patients were randomly assigned to receive either gefitinib or cisplatin plus docetaxel (given every 21 days for three to six cycles). The primary end point was PFS.[56]

Another phase III trial from Japan also prospectively confirmed that patients with NSCLC and EGFR variants have improved PFS but not OS when treated with gefitinib. In the second trial, the West Japanese Oncology Group conducted a phase III study (WJTOG3405) in 177 chemotherapy-naïve patients aged 75 years or younger and diagnosed with stage IIIB/IV NSCLC or postoperative recurrence and EGFR variants (either the EGFR exon 19 deletion or EGFR L858R single nucleotide variant). Patients were randomly assigned to receive either gefitinib or cisplatin plus docetaxel (given every 21 days for three to six cycles). The primary end point was PFS.[56]

The gefitinib group had significantly longer PFS than the cisplatin-plus-docetaxel group, with a median PFS of 9.2 months (95% CI, 8.0–13.9) versus 6.3 months (range, 5.8–7.8 months; HR, 0.489; 95% CI, 0.336–0.710; log-rank P < .0001).[56][Level of evidence B1]