COMBINATION CHEMOTHERAPY BETTER FOR PS-2 NSCLC PATIENTS 

NEW YORK (Reuters Health) Jun 21 - Carboplatin plus pemetrexed improves survival over pemetrexed alone in ambulatory patients with advanced non-small-cell lung cancer (NSCLC), randomized trial data show.

The phase III trial "establishes combination chemotherapy as the standard of care" for patients with advanced NSCLC and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2, Dr. Rogerio C. Lilenbaum from Yale Cancer Center, New Haven, Connecticut, told Reuters Health.

The lack of agreement on optimal therapy for these patients, who account for a significant percentage of those with advanced NSCLC, led Dr. Lilenbaum and colleagues to test pemetrexed monotherapy against pemetrexed plus carboplatin for first-line management.

As reported June 17 online in the Journal of Clinical Oncology, the researchers assigned 102 patients to pemetrexed (P) and 103 to the combination (CP), at eight centers in Brazil and one in the U.S.

During a median follow-up of 27.5 months, objective response rates among evaluable patients were significantly higher in the CP arm (19/79, 24%) than in the P arm (7/67, 10.5%; p=0.032).

Results were similar among all randomly assigned patients (18.4% vs 6.9%, respectively).

Median progression-free survival was 2.8 months with monotherapy and 5.8 months with CP (p<0 .001="" 12="" 17="" 2="" also="" and="" cp="" higher="" monotherapy="" months="" p="" progression-free="" rates="" six="" survival="" than="" were="" with="">

These differences translated into superior median survival times for CP (9.3 vs 5.3 months), as well as superior survival at six months (66.8% vs 44.9%) and at 12 months (40.1% vs 21.9%).

The superiority of the combination regimen persisted after excluding patients with squamous cell carcinoma and unknown histology (i.e., a pure pemetrexed-eligible population).

Results were similar among separately analyzed subsets of elderly patients and active/former smokers, whereas median survival times were not significantly different between CP and P for never-smokers.

An exploratory analysis found no significant difference in median survival in groups with no comorbidities, one comorbidity, and one or more comorbidities.

As might be expected, hematologic toxicity, albeit mild, was more common in the combination arm than in the pemetrexed arm of the study. Febrile neutropenia occurred with similar frequency in the two arms, however.

"To our knowledge," the researchers say, "our study is the first to demonstrate that combination chemotherapy conclusively improves survival compared with single-agent therapy in patients with ECOG PS of 2."

"Because this trial used pemetrexed (Alimta), the vast majority of patients had a non-squamous histology," Dr. Lilenbaum said. "However, our results can be extended to patients with squamous histology, who can benefit from a different combination regimen (carboplatin + a taxane for example)."

"In PS 2 patients whose tumors harbor actionable mutations (primarily EGFR and ALK), targeted agents are the treatment of choice," Dr. Lilenbaum said.

"Patients with advanced NSCLC and a PS of 2 benefit from more aggressive therapy and should not be denied a combination regimen on the basis of their PS alone," Dr. Lilenbaum concluded. "These patients are quite prevalent in clinical practice (approximately 30-40% of advanced NSCLC patients)."

SOURCE: http://bit.ly/19o4vYP

J Clin Oncol 2013.