Study reveals that patients with NSCLC who received maintenance therapy with ALIMTA showed survival benefit

Eli Lilly and CompanySep 21 2009

Data published today in The Lancet showed a survival benefit in nonsquamous patients with advanced non-small cell lung cancer (NSCLC) who received maintenance therapy with ALIMTA(R) (pemetrexed for injection) plus best supportive care as compared to placebo plus best supportive care.

This Phase III clinical trial supported previous studies looking at the use of histology to tailor treatment with ALIMTA for patients with advanced nonsquamous NSCLC. Advanced nonsquamous NSCLC patients on the ALIMTA plus best supportive care arm achieved more than five months increased median overall survival compared to nonsquamous NSCLC patients who received placebo plus best supportive care following initial chemotherapy.

The publication of The Lancet manuscript follows the July 2009 U.S. Food and Drug Administration (FDA) approval of ALIMTA as maintenance therapy for patients with locally advanced or metastatic nonsquamous NSCLC, whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. ALIMTA is not indicated for treatment in patients with squamous cell NSCLC. The European Commission also granted a similar approval in July 2009.

NSCLC is defined as a group of histologies, that is, tumor types differentiated by cellular structure. Nonsquamous histology includes adenocarcinoma and large cell carcinoma - which account for about 70 percent of all NSCLC diagnoses(1) - as well as histologies classified as "other." About 30 percent of all NSCLC cases are squamous.(2)

Maintenance therapy is a relatively new concept in NSCLC treatment, according to study lead author Chandra P. Belani, M.D., Miriam Beckner distinguished professor of medicine and deputy director of Penn State Cancer Institute at Penn State Milton S. Hershey Medical Center in Hershey, Pa.

"Previously, we would treat patients with advanced non-small cell lung cancer with four cycles of a platinum-based therapy, and then wait for a recurrence before treating again," said Dr. Belani. "The results of this study are provocative and introduce the concept of maintenance therapy for patients with non-small cell lung cancer."

"What makes these findings more compelling is a survival advantage exceeding five months with ALIMTA for patients with nonsquamous cell histologies. The degree of patient benefit is substantial," added Dr. Belani.

"This study is very encouraging for our fight against this deadly disease," added Richard Gaynor, M.D., Lilly's vice president of cancer research and global oncology platform leader. "First, it makes a case for maintenance therapy in advanced, nonsquamous NSCLC. Secondly, it showcases the importance of histology in tailoring a treatment to the nonsquamous NSCLC patient."

The Lancet manuscript of ALIMTA as a maintenance therapy for advanced nonsquamous NSCLC summarized findings from a global, multicenter, double-blind Phase III trial that was presented by Dr. Belani in an oral presentation at the American Society of Clinical Oncology (ASCO) annual meeting in Orlando, Fla. on May 31, 2009.(3)

The trial compared the efficacy of ALIMTA plus best supportive care versus placebo plus best supportive care in 663 patients with stage IIIB/IV NSCLC whose disease had not progressed after four cycles of platinum-based induction chemotherapy.

According to the results, patients treated with ALIMTA demonstrated statistically superior overall survival compared to those treated with placebo (13.4 months vs. 10.6 months). But when breaking down the data by histology, researchers found nonsquamous patients on the ALIMTA arm achieved 15.5 months median overall survival compared to 10.3 months for nonsquamous patients on the placebo arm. Patients with squamous cell carcinoma who were treated with ALIMTA did not see an improvement in overall survival as compared to placebo (9.9 vs. 10.8 months, respectively).

Patients in the trial were treated with ALIMTA (500 mg/m2 on day one of each 21-day cycle) or placebo. All patients were supplemented with vitamin B12, folic acid and dexamethasone.

Drug-related grade 3/4 toxicities were higher for those treated with ALIMTA vs. placebo (16% vs. 4%); specifically, anemia (3% vs. 1%), neutropenia (3% vs. 0%), leucopenia (2% vs. 1%), fatigue (5% vs. 1%), anorexia (2% vs. 0%), mucositis/stomatitis (1% vs. 0%), diarrhea (1% vs. 0%), infection (2% vs. 0%), and neuropathy-sensory (1% vs. 0%). Increases in adverse reactions (all grades) were observed with longer exposure. Grade 3/4 toxicities did not increase significantly in patients who received greater than or equal to six cycles and greater than or equal to ten cycles of ALIMTA.

ALIMTA is also approved for: first-line treatment of advanced, nonsquamous NSCLC in combination with a platinum-based chemotherapy; as a single agent in the second-line setting for advanced, nonsquamous NSCLC patients with recurrent disease; and in combination with cisplatin as a treatment for patients with malignant pleural mesothelioma, whose disease is unresectable or who are otherwise not candidates for curative surgery.

For full prescribing and safety information about ALIMTA, visit www.ALIMTA.com.