ASCO Preview Highlights Study Of Alimta For First-Line NSCLC

Maintenance therapy with Lilly’s pemetrexed shows increase in progression-free survival in the only drug-related abstract in ASCO’s press call.

Kicking off the early release of abstracts from the American Society of Clinical Oncology annual meeting, ASCO highlighted results of a Phase III study of Eli Lilly's Alimta in advanced first-line non-small cell lung cancer showing that maintenance therapy with pemetrexed delayed progression by 50 percent.

Until now, maintenance therapy has not been proven valuable and is not part of the standard of care.

The Phase III trial analyzed progression-free survival and overall survival in 663 patients with advanced NSCLC whose cancer was stable following induction therapy with a platinum-containing drug.

Progression-free survival was significantly longer in patients who received pemetrexed (n=441) compared to those who received placebo (n=222): 4.3 months versus 2.6 months. The side effect profile was similar in the two groups.

ASCO President-elect Richard L. Schilsky pointed out that the results seem particularly prominent in patients with the adenocarcinoma histology, with mean PFS of 4.7 months. Since pemetrexed is a drug that works best in tumors that are rapidly proliferating, he hypothesized that "it may well be that that is a reason that the effects are more prominent" in the adenocarcinoma histology.

The treatment-by-histology findings were that there was a consistent improvement with pemetrexed treatment in non-squamous histologies. However," in the squamous population there was little change in PFS with pemetrexed therapy," lead investigator Tudor Ciuleanu, University of Medicine and Pharmacy, Romania, noted during the ASCO press call. The result was "consistent with previous Phase III trials," he said.

Preliminary overall survival results were also presented, based on the first 300 events of a planned 475. The initial finding was an additional 13 months of survival for pemetrexed patients compared to 10.2 months with placebo, a 20 percent reduction in the risk of death with pemetrexed therapy.

However, Ciuleanu cautioned that the findings for overall survival are still preliminary and are not statistically significant. The final survival analysis is expected to occur in the next six to 12 months.

"It's too soon to say yet whether [the improvement in PFS] will result in improvement in overall survival," Schilsky said on the call. "I think one of the questions that the study raises is, in fact, whether if one simply used pemetrexed in its current indication, that is, at the time of progression, whether or not one would get a similar overall survival." He added that it will be important to know to what extent the patients in the control group eventually received pemetrexed as part of their second-line chemotherapy.

Alimta is currently marketed as a second-line treatment for NSCLC after progression on first-line chemotherapy, based on response rate data, and for first-line treatment of malignant pleural mesothelioma ¹ (Also see "Lilly Alimta To Be Available In Two Weeks Following Five-Month Review" - Pink Sheet, 5 Feb, 2004.).

Schilsky raised a number of other questions in response to the study: "Is this finding unique to pemetrexed? Would one find similar results by giving another active anti-cancer drug after the initial period of chemotherapy? Or would one find similar results simply by continuing with the first-round of chemotherapy in patients who had stable or responding disease?"

Lilly has no other studies underway in first-line NSCLC. The firm told "The Pink Sheet" DAILY it is in talks with FDA about seeking such an indication.

The Alimta study was the only drug-related abstract to be included in ASCO's press preview for the annual meeting, to be held in Chicago May 30 - June 2. The call was part of ASCO's new abstract policy: In an attempt to get ahead of the typical leaks of abstracts before the meeting - which result in market fluctuations - the organization released the majority of the abstracts at 9 p.m. on May 15.

-Lauren Smith ([email protected])

[Editor's note: Check back with "The Pink Sheet" DAILY for additional coverage of the newly released ASCO abstracts.]