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Lung Cancer Drug Alimta (Pemetrexed) Stumbles in Phase III Trial

No significant difference between pemetrexed/cisplatin regimen and etoposide/cisplatin

Eli Lilly and Company has announced that final results from the phase III PROCLAIM trial will be presented at the upcoming American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

PROCLAIM was a randomized superiority study of patients with locally advanced, nonsquamous non–small-cell lung cancer (NSCLC) in which a regimen consisting of Alimta (pemetrexed for injection) in combination with cisplatin with concurrent radiation, followed by maintenance Alimta, was compared with etoposide and cisplatin plus concurrent radiation, followed by consolidation chemotherapy of the oncologist’s choice.

Lilly announced in 2012 that enrollment into the PROCLAIM trial was halted because an independent data monitoring committee projected that the experimental arm of the study would not meet its primary endpoint of superior overall survival. As no new safety issues were identified, all of the patients who received treatment with the pemetrexed regimen were allowed to continue their assigned therapy at the discretion of the investigator and were followed for survival. The results from this investigation are being presented at the ASCO meeting.

In the PROCLAIM trial, patients with nonsquamous NSCLC were treated in the first-line setting with pemetrexed plus cisplatin and concurrent thoracic radiation therapy (n = 283) or with etoposide plus cisplatin and concurrent radiation (n = 272). Patients in the pemetrexed arm received subsequent treatment with additional doses of single-agent pemetrexed, and patients in the etoposide arm received consolidated chemotherapy (either more etoposide/cisplatin or new treatment with vinorelbine/cisplatin or paclitaxel/carboplatin), as selected by the treating oncologist.

The patients treated in the pemetrexed arm achieved a median overall survival of 26.8 months compared with 25.0 months for those treated in the etoposide arm (hazard ratio [HR], 0.98; P = 0.831). Median progression-free survival was 11.4 months in the pemetrexed arm compared with 9.8 months in the etoposide arm (HR, 0.86; P = 0.130), and the overall response rates were 35.9% and 33.0% in the two treatment arms, respectively.

Grade 3/4 adverse events occurred in 64.0% of patients in the pemetrexed arm and in 76.8% of those in the etoposide arm. The rate of grade 3/4 neutropenia/granulocytopenia was lower in the pemetrexed arm compared with the etoposide arm (24.4% vs. 44.5%, respectively; P < 0.0001), as were the rates of pneumonitis/pulmonary infiltrates (1.8% vs. 2.6%) and esophagitis (15.5% vs. 20.6%).

In 2004, Alimta received consecutive approvals: it was the first agent to be approved in combination with cisplatin as a treatment for patients with malignant pleural mesothelioma whose disease was unresectable or who were otherwise not candidates for curative surgery, and then as a single agent for the second-line treatment of patients with locally advanced or metastatic NSCLC after prior chemotherapy.

In 2008, Alimta, in combination with cisplatin, was approved as a first-line treatment for locally advanced or metastatic NSCLC in patients with nonsquamous histology. At the time of this first-line approval, the FDA also approved a change to the drug’s second-line indication. Alimta is now indicated as a single agent for the treatment of patients with locally advanced or metastatic, nonsquamous NSCLC after prior chemotherapy.

In 2009, Alimta was approved as maintenance therapy for locally advanced or metastatic NSCLC, specifically for patients with a nonsquamous histology whose disease had not progressed after four cycles of platinum-based first-line chemotherapy. In 2012, Alimta received further approval as “continuation” maintenance therapy after first-line Alimta plus cisplatin for locally advanced or metastatic nonsquamous NSCLC.

Alimta is not indicated for the treatment of patients with squamous-cell NSCLC. Myelosuppression is usually the dose-limiting toxicity with Alimta therapy.

Source: Eli Lilly; May 28, 2015.


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