Second-line Treatments Tested in Patients with Non-Small Cell Lung Cancer

Docetaxel superior to erlotinib in wild-type EGFR setting, while maintenance pemetrexed prolongs survival in advanced disease

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Results of two late-breaking phase III trials presented at 2012 ASCO Annual Meeting add to the evolving understanding of how best to treat non–small cell lung cancer (NSCLC). The TAILOR trial suggested the benefit of chemotherapy over EGFR-targeted therapy as second-line treatment of patients with wild-type EGFR NSCLC.1 The PARAMOUNT trial found that maintenance pemetrexed (Alimta) plus best supportive care improved overall survival compared with placebo plus best supportive care following induction therapy with pemetrexed/cisplatin in patients with advanced nonsquamous NSCLC.2

TAILOR Results

Docetaxel was superior to erlotinib (Tarceva) in prolonging progression-free survival as second-line treatment of NSCLC patients with wild-type EGFR, according to results of the phase III TAILOR trial. The primary endpoint of this trial is overall survival, but survival data are not yet mature. At the ASCO Annual Meeting, Marina Chiara Garassino, MD, U.O. Oncologia Medica, A.O. Fatebenefratelli e Oftalmico, Milan, Italy, presented progression-free survival, overall response, and safety data from TAILOR.

“TAILOR is the only prospective head-to-head trial comparing erlotinib vs docetaxel in wild-type EGFR NSCLC. Docetaxel significantly improved progression-free survival, response rates, and disease control rates. The reported toxicity with both drugs was as expected. KRAS was not predictive of response or progression-free survival. TAILOR preliminary results do not support the use of erlotinib in wild-type EGFR patients with NSCLC, and survival data are awaited,” concluded Dr. Garassino.

Patients enrolled in TAILOR had histologically confirmed wild-type EGFR and assessment of KRAS status, and results were cross-validated in two independent labs. All patients received previous platinum-based chemotherapy, but previous chemotherapy with taxanes and other anti-EGFR agents was excluded. The investigators randomly assigned 222 patients 1:1 to docetaxel or erlotinib. Third-line treatment was allowed at progression, but crossover to the other treatment arm was not allowed. Patients were stratified according to treatment center, recurrent NSCLC, or progressive NSCLC, and type of first-line chemotherapy.

Key Data

In an intent-to-treat analysis of 219 patients at 6 months, 28.9% were free of progression in the docetaxel arm vs 16.9% in the erlotinib arm. These results held up in a multivariate analysis. No significant interaction was seen between treatment arm and KRAS status.

“KRAS mutations do not seem to be predictive or prognostic in second-line therapy of NSCLC,” Dr. Garassino commented.

The rate of disease control was double in the docetaxel arm, but as expected, more hematologic toxicities were reported with the chemotherapy. The rate of patients with one or more serious adverse events was similar in both arms: 14.4% in the docetaxel arm and 13.1% in the erlotinib arm.


The phase III PARAMOUNT trial found that continuous maintenance therapy with pemetrexed prolonged overall survival compared with placebo in patients with advanced nonsquamous NSCLC who first received induction therapy with four cycles of pemetrexed/cisplatin. Previous results showed improved progression-free survival with maintenance pemetrexed, and the new survival data confirm a persistent benefit with maintenance pemetrexed.

“This study shows that maintenance therapy with pemetrexed offers superior overall survival compared with placebo. These final results confirm that pemetrexed/cisplatin induction followed by continuous pemetrexed further benefits patients compared with induction therapy alone, offering a change in the treatment paradigm for advanced nonsquamous NSCLC,” stated presenting author Luis Paz-Ares, MD, University Hospital–Virgen del Rocio, Seville, Spain.

In the overall trial, 939 received induction therapy; 539 patients without disease progression were randomized 2:1 to pemetrexed plus best supportive care or placebo plus best supportive care.

Major Results

At 12 months, overall survival was 58% in the pemetrexed arm vs 45% in the placebo arm; at 24 months, overall survival rates were 32% vs 21%, respectively. Median overall survival from the time of induction therapy was 16.9 vs 14 months (P = .019), respectively, representing a 22% increase in survival among those who received maintenance pemetrexed.

The rate of complete or partial response was 45% at baseline. Survival did not differ for those with a complete or partial response or stable disease after induction, Dr. Paz-Ares said. ■

Disclosure: Dr. Garassino is an advisor for Eli Lilly. Dr. Paz-Ares has been a consultant or advisor for and received honoraria from Bayer, Lilly, Pfizer, and Roche.


1. Garassino MC, Martelli O, Bettini A, at al: TAILOR: A phase III trial comparing erlotinib with docetaxel as the second-line treatment of NSCLC patients with wild-type (wt) EGFR. 2012 ASCO Annual Meeting. Abstract LBA7501. Presented June 4, 2012.

2. Paz-Ares L, De Marinis F, Dediu M, et al: PARAMOUNT: Final overall survival (OS) results of the phase III study of maintenance pemetrexed plus best supportive care versus placebo plus BSC immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer (NSCLC). 2012 ASCO Annual Meeting. Abstract LBA7507. Presented June 4, 2012.

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