Eli Lilly to present results of two Phase II trials evaluating ALIMTA in combination with chemotherapy, radiation

Results of two Phase II trials evaluating ALIMTA® (pemetrexed for injection) in combination with a platinum chemotherapy and radiation for patients with locally advanced non-small cell lung cancer (NSCLC) will be presented by Eli Lilly and Company at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill., on June 6, 2010.

The standard of care for many patients with unresectable stage IIIA/B NSCLC is a concurrent treatment of chemotherapy and radiation, but the chosen chemotherapy varies by oncologist.  Previous study results for an ALIMTA-based regimen in this therapeutic area warranted further study.

The Phase II study (ASCO Abstract #7087) evaluated 39 patients with unresectable stage IIIA/B NSCLC who were treated with full doses of ALIMTA and cisplatin and a full dose of concurrent radiation. Patients on the ALIMTA regimen achieved a median overall survival of 19.7 months and median progression-free survival of 11.8 months.  Eighty percent of patients continued to live one year following initial treatment and 47 percent of patients were living for one year without tumor progression.  The single-arm trial accrued patients across five centers in Canada.  

Ten patients experienced grade 3/4 hematologic toxicity, particularly neutropenia (low white blood cell count).  Non-hematologic toxicities were also observed, including grade 3 nausea/vomiting, espohagitis (inflammation of the esophagus), serum sodium and potassium alterations, fatigue, and pneumonitis (inflammation of lung tissue) and grade 4 hypotension (low blood pressure).

"Early results from this Phase II study supported continuing to evaluate both of these agents at full dose," said Richard Gaynor, M.D., vice president of oncology product development and medical affairs at Lilly. "Likewise, this final Phase II evidence supports the rationale for our ongoing Phase III trial, PROCLAIM, where we are evaluating ALIMTA+cisplatin+radiation followed by ALIMTA alone as maintenance therapy in locally advanced stage III NSCLC in nonsquamous cell histology."

Another Phase II study (ASCO Abstract #7082) evaluated patients with inoperable stage IIIA/B NSCLC with a treatment regimen of ALIMTA plus either carboplatin or cisplatin along with concurrent radiation therapy.  Results from those treated on the ALIMTA+carboplatin+radiation arm found 6.7% achieving a complete response, 40% with a partial response, 46.7% with stabilized disease and 6.7% with progressive disease.  Results of those treated on the ALIMTA+cisplatin+radiation arm found 5% achieving a complete response, 55% with a partial response, 25% with stabilized disease and 15% with progressive disease.  

Grade 3/4 toxicities on the carboplatin arm included neutropenia, thrombocytopenia (low platelet count), esophogitis, fatigue, anemia (low red blood cell count) and dysphagia (difficulty in swallowing).  Grade 3 toxicities on the cisplatin arm were neutropenia, esophogitis, fatigue and anemia, while one instance of grade 4 esophogitis was observed.

PROCLAIM Trial

Further evaluation of ALIMTA in this therapeutic setting is currently ongoing with the Phase III PROCLAIM study.  The trial seeks to evaluate ALIMTA+cisplatin+radiation followed by ALIMTA alone as maintenance therapy versus etoposide+cisplatin+radiation followed by consolidation cytotoxic chemotherapy of choice in locally advanced stage III NSCLC in nonsquamous cell histology.  The primary outcome is overall survival, and secondary outcomes include progression-free survival, toxicities, and 1-, 2-, and 3-year survival rates. Radiation quality control is a key component of the trial.