Afatinib

An open-label, randomized, phase III study (LUX-Lung 3 [NCT00949650]) included 345 Asian (72%) and White (26%) patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other [38 of 345 patients had other less-common EGFR variants]). Patients were screened, and 340 patients received at least one dose of study medication, which was either 40 mg of oral afatinib, an irreversible EGFR/human epidermal receptor TKI, daily or up to six cycles of cisplatin and pemetrexed for first-line treatment.[60]

An open-label, randomized, phase III study (LUX-Lung 3 [NCT00949650]) included 345 Asian (72%) and White (26%) patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other [38 of 345 patients had other less-common EGFR variants]). Patients were screened, and 340 patients received at least one dose of study medication, which was either 40 mg of oral afatinib, an irreversible EGFR/human epidermal receptor TKI, daily or up to six cycles of cisplatin and pemetrexed for first-line treatment.[60]

The primary end point was PFS. In this study, the afatinib group had significantly longer PFS than the cisplatin-plus-pemetrexed group, with a median PFS of 11.1 months for afatinib and 6.9 months for chemotherapy (HR, 0.58; 95% CI, 0.43–0.78; P = .001).[60][Level of evidence B1]

An open-label, randomized, phase III study (LUX-Lung 3 [NCT00949650]) included 345 Asian (72%) and White (26%) patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other [38 of 345 patients had other less-common EGFR variants]). Patients were screened, and 340 patients received at least one dose of study medication, which was either 40 mg of oral afatinib, an irreversible EGFR/human epidermal receptor TKI, daily or up to six cycles of cisplatin and pemetrexed for first-line treatment.[60]

Assessment of OS was a secondary end point and was reported separately.[61] Similar to the PFS analysis, OS was stratified based on EGFR variant type and the patient's ethnic origin.

An open-label, randomized, phase III study (LUX-Lung 3 [NCT00949650]) included 345 Asian (72%) and White (26%) patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other [38 of 345 patients had other less-common EGFR variants]). Patients were screened, and 340 patients received at least one dose of study medication, which was either 40 mg of oral afatinib, an irreversible EGFR/human epidermal receptor TKI, daily or up to six cycles of cisplatin and pemetrexed for first-line treatment.[60] › Assessment of OS was a secondary end point and was reported separately.[61] Similar to the PFS analysis, OS was stratified based on EGFR variant type and the patient's ethnic origin.

With a median follow-up of 41 months, median OS was 28.2 months in patients in both arms (HR, 0.88; 95% CI, 0.66–1.17; P = .39).

An open-label, randomized, phase III study (LUX-Lung 3 [NCT00949650]) included 345 Asian (72%) and White (26%) patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other [38 of 345 patients had other less-common EGFR variants]). Patients were screened, and 340 patients received at least one dose of study medication, which was either 40 mg of oral afatinib, an irreversible EGFR/human epidermal receptor TKI, daily or up to six cycles of cisplatin and pemetrexed for first-line treatment.[60] › Assessment of OS was a secondary end point and was reported separately.[61] Similar to the PFS analysis, OS was stratified based on EGFR variant type and the patient's ethnic origin.

In patients with common EGFR variants (i.e., EGFR exon 19 deletion or EGFR L858R variant), survival did not differ significantly between treatment arms (HR, 0.78; 95% CI, 0.58–1.06; P = .11). However, prespecified subgroup analyses demonstrated a survival advantage with afatinib compared with chemotherapy in patients with EGFR del19 variants (median OS, 33.3 months vs. 21.1 months; HR, 0.54; 95% CI, 0.36–0.79; P = .0015) but no significant difference between treatment arms in patients with EGFR L858R variants (median OS, 27.6 months vs. 40.3 months; HR, 1.30; 95% CI, 0.80–2.11; P = .29).

An open-label, randomized, phase III study (LUX-Lung 3 [NCT00949650]) included 345 Asian (72%) and White (26%) patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other [38 of 345 patients had other less-common EGFR variants]). Patients were screened, and 340 patients received at least one dose of study medication, which was either 40 mg of oral afatinib, an irreversible EGFR/human epidermal receptor TKI, daily or up to six cycles of cisplatin and pemetrexed for first-line treatment.[60] › Assessment of OS was a secondary end point and was reported separately.[61] Similar to the PFS analysis, OS was stratified based on EGFR variant type and the patient's ethnic origin.

First-line afatinib was associated with a significant survival advantage compared with chemotherapy in patients with NSCLC and EGFR del19 variants, but not in patients with EGFR L858R variants or in the overall EGFR-positive patient population.[61][Level of evidence A1]

An open-label phase III study (LUX-Lung 6 [NCT01121393]) included 364 East Asian patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other EGFR variants). Patients were randomly assigned in a 2:1 ratio to receive 40 mg of afatinib daily or gemcitabine and cisplatin for up to six cycles for first-line treatment.[62]

An open-label phase III study (LUX-Lung 6 [NCT01121393]) included 364 East Asian patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other EGFR variants). Patients were randomly assigned in a 2:1 ratio to receive 40 mg of afatinib daily or gemcitabine and cisplatin for up to six cycles for first-line treatment.[62]

The primary end point was PFS. Median PFS was significantly longer in the afatinib group (11.0 months; 95% CI, 9.7–13.7) than in the gemcitabine and cisplatin group (5.6 months, [range, 5.1–6.7 months]; HR, 0.28; 95% CI, 0.20–0.39; P < .0001).[62][Level of evidence B1]

An open-label phase III study (LUX-Lung 6 [NCT01121393]) included 364 East Asian patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other EGFR variants). Patients were randomly assigned in a 2:1 ratio to receive 40 mg of afatinib daily or gemcitabine and cisplatin for up to six cycles for first-line treatment.[62]

Assessment of OS was a prespecified secondary end point and was reported separately.[61] Similar to the PFS analysis, OS was stratified on the basis of EGFR variant type and the patient's ethnic origin.

An open-label phase III study (LUX-Lung 6 [NCT01121393]) included 364 East Asian patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other EGFR variants). Patients were randomly assigned in a 2:1 ratio to receive 40 mg of afatinib daily or gemcitabine and cisplatin for up to six cycles for first-line treatment.[62] › Assessment of OS was a prespecified secondary end point and was reported separately.[61] Similar to the PFS analysis, OS was stratified on the basis of EGFR variant type and the patient's ethnic origin.

With a median follow-up of 33 months, median OS was 23.1 months in patients in the afatinib arm and 23.5 months in patients in the chemotherapy arm (HR, 0.93; 95% CI, 0.72–1.22; P = .61).

An open-label phase III study (LUX-Lung 6 [NCT01121393]) included 364 East Asian patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other EGFR variants). Patients were randomly assigned in a 2:1 ratio to receive 40 mg of afatinib daily or gemcitabine and cisplatin for up to six cycles for first-line treatment.[62] › Assessment of OS was a prespecified secondary end point and was reported separately.[61] Similar to the PFS analysis, OS was stratified on the basis of EGFR variant type and the patient's ethnic origin.

In patients with common EGFR variants (i.e., EGFR exon 19 deletion or EGFR L858R variant), survival did not differ significantly between treatment arms (HR, 0.83; 95% CI, 0.62–1.09; P = .18). However, prespecified subgroup analyses demonstrated a survival advantage with afatinib compared with chemotherapy in patients with EGFR del19 variants (median OS, 31.4 months vs. 18.4 months; HR, 0.64; 95% CI, 0.44–0.94; P = .023), but no significant difference between treatment arms was seen in patients with EGFR L858R variants (median OS, 19.6 months vs. 24.3 months; HR, 1.22; 95% CI, 0.81–1.83; P = .34).

An open-label phase III study (LUX-Lung 6 [NCT01121393]) included 364 East Asian patients with stage IIIB/IV NSCLC and confirmed EGFR variants (i.e., EGFR exon 19 deletion, EGFR L858R variant, or other EGFR variants). Patients were randomly assigned in a 2:1 ratio to receive 40 mg of afatinib daily or gemcitabine and cisplatin for up to six cycles for first-line treatment.[62] › Assessment of OS was a prespecified secondary end point and was reported separately.[61] Similar to the PFS analysis, OS was stratified on the basis of EGFR variant type and the patient's ethnic origin.

First-line afatinib was associated with a significant survival advantage compared with chemotherapy in patients with NSCLC and EGFR del19 variants but not in patients with EGFR L858R variants or in the overall EGFR-positive patient population.[61][Level of evidence A1]