The label update is based on data from PARAMOUNT, a Phase III trial presented in June at the American Society of Clinical Oncology (ASCO) 2012 annual meeting[i] that showed ALIMTA improved overall survival as continuous maintenance therapy in patients with advanced, nonsquamous NSCLC. In October 2011, in Europe, the continuation maintenance label for ALIMTA was approved on progression-free survival and interim overall survival data from the same trial. The label has now been updated to include final survival results.
In Europe, ALIMTA is a chemotherapy agent currently approved for first-line treatment of patients with locally advanced or metastatic NSCLC other than predominantly squamous cell histology in combination with cisplatin; as a single agent in the second-line setting for advanced, other than predominantly squamous NSCLC patients with recurrent disease; and as a monotherapy for maintenance treatment of patients following platinum-based chemotherapy with other than predominantly squamous cell histology in locally advanced or metastatic NSCLC. ALIMTA is not indicated for patients with squamous cell NSCLC. ALIMTA is also approved, in combination with cisplatin for the treatment of chemotherapy naive patients with unresectable malignant pleural mesothelioma.
“This is the first treatment option that provides patients and physicians with a regimen that has demonstrated an improvement in overall survival in continuation maintenance,” said Richard Gaynor, M.D., vice president of product development and medical affairs for Lilly Oncology. “ALIMTA is now proven to extend lives for patients with this type of lung cancer beginning in first-line treatment and continuing through maintenance therapy.”
“Continuation maintenance” involves continuing one of the same medicines prescribed in first-line treatment as maintenance therapy, in an effort to extend survival. It is the most recent addition to a new paradigm of maintenance treatment for advanced, nonsquamous non-small cell lung cancer. Prior to the use of maintenance therapy, physicians typically treated a patient with four to six cycles of chemotherapy and then waited until the disease returned or worsened before resuming treatment.
This latest approval for ALIMTA follows the recent approval by the U.S. Food and Drug Administration (FDA) of ALIMTA as a continuation maintenance therapy for locally advanced or metastatic nonsquamous NSCLC, following first-line therapy with ALIMTA-cisplatin in patients with a nonsquamous histology.
A total of 939 patients with advanced, nonsquamous NSCLC were enrolled in the study and received ALIMTA (500 mg/m2 on day one of a 21-day cycle) in combination with cisplatin (75 mg/m2) induction therapy. All patients received vitamin B12, folic acid and dexamethasone. Patients whose disease had not progressed during the ALIMTA-cisplatin induction and who had an ECOG performance status of 0-1 (n=539) were randomized two-to-one to receive ALIMTA maintenance (500 mg/m2 on day one of a 21-day cycle) plus best supportive care (n=359) or placebo plus best supportive care (n=180) until disease progression. Of the patients whose disease had not progressed during ALIMTA-cisplatin induction therapy and who were randomized to receive maintenance therapy, 44 percent versus 42 percent achieved a complete response or partial response to induction therapy and 53 percent versus 53 percent had stable disease after induction treatment in the ALIMTA and placebo arms, respectively.
Final PARAMOUNT results demonstrated a statistically significant 22 percent reduction in the risk of death (HR=0.78; 95% CI: 0.64–0.96; p=0.0195), with ALIMTA compared to placebo. This reduction in the risk of death resulted in an improved median overall survival, from the time patients were randomized, of 13.9 months median for patients receiving ALIMTA, compared to 11.0 months median for patients on the placebo arm.
Median, independently reviewed, progression-free survival measured from randomization was 3.9 months on the ALIMTA arm as compared to 2.6 months on the placebo arm with a hazard ratio of 0.64. Stated another way, the study showed that patients on the ALIMTA continuation maintenance arm had a 36 percent improvement of survival without disease worsening, compared to the placebo arm.
The most frequently observed adverse reactions (all grades) across both maintenance trials with ALIMTA as a single agent versus placebo, respectively, were anemia (18.0 percent versus 5.2 percent); leucopenia (5.8 percent versus 0.7 percent); neutropenia (8.4 percent versus 0.2 percent); fatigue (24.1 percent versus 10.9 percent); neuropathy-sensory (7.4 percent versus 5.0 percent); nausea (17.3 percent versus 4.0 percent); vomiting (8.4 percent versus 1.5 percent); anorexia ( 12.8 percent versus 3.2 percent); mucositis/stomatitis (6.8 percent versus 1.7 percent); rash/desquamation (8.1 percent versus 3.7 percent); ALT elevation (6.5 percent versus 2.2 percent); AST elevation (5.9 percent versus 1.7 percent); renal disorders (7.6 percent versus 1.7 percent); pain (7.6 percent and 4.5 percent) and edema (5.6 percent versus 1.5 percent).
Lung cancer has long been the most common cancer in the world, representing nearly 13 percent of all new cancers and causing nearly 1.4 million deaths annually.[ii] About 85 – 90 percent of all lung cancers are NSCLC.[iii] The liver, bones and brain are potential targets if the cancerous cells spread to other areas in the body.
NSCLC comprises a group of histologies or tumor types differentiated by cellular structure. Nonsquamous histology includes adenocarcinoma and large cell carcinoma, which account for more than half of all NSCLC diagnoses,[iv] as well histologies classified as “other.”
About Lilly Oncology
For more than four decades, Lilly Oncology, a division of Eli Lilly and Company, has been dedicated to delivering innovative solutions that improve the care of people living with cancer. Because no two cancer patients are alike, Lilly Oncology is committed to developing novel treatment approaches. To learn more about Lilly’s commitment to cancer, please visit www.LillyOncology.com.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers – through medicines and information – for some of the world’s most urgent medical needs.
This press release contains forward-looking statements about the potential of ALIMTA for the treatment of non-small cell lung cancer and reflects Lilly’s current beliefs. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development, commercialization, and regulatory review. There is no guarantee that the product will continue to be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly’s filings with the United States Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.[i] Paz-Ares L. G., et al. PARAMOUNT: Phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo plus BSC immediately following induction treatment with pem plus cisplatin for advanced nonsquamous non-small cell lung cancer (NSCLC).J Clin Oncol 29: 2011 (suppl; abstr CRA7510). [ii] World Health Organization International Agency for Research in Cancer, GLOBOCAN 2008, Section of Cancer Information, http://globocan.iarc.fr/