From Mass General: Pemetrexed-based chemotherapy in patients with advanced, ALK-positive lung cancer

http://www.ncbi.nlm.nih.gov/pubmed/22887466

Ann Oncol. 2012 Aug 10. [Epub ahead of print]

Pemetrexed-based chemotherapy in patients with advanced, ALK-positive non-small cell lung cancer.

Shaw AT, Varghese AM, Solomon BJ, Costa DB, Novello S, Mino-Kenudson M, Awad MM, Engelman JA, Riely GJ, Monica V, Yeap BY, Scagliotti GV.

Source

Department of Medicine Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston.

Abstract

Background  

Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib. To determine whether ALK-positive NSCLC is also sensitive to pemetrexed, we retrospectively evaluated progression-free survival (PFS) of ALK-positive versus ALK-negative patients who had been treated with pemetrexed-based chemotherapy for advanced NSCLC.

Patients and methods

We identified 121 patients with advanced, ALK-positive NSCLC in the USA, Australia, and Italy. For comparison, we evaluated 266 patients with advanced, ALK-negative, epidermal growth factor receptor (EGFR)-wild-type NSCLC, including 79 with KRAS mutations and 187 with wild-type KRAS (WT/WT/WT). We determined PFS on different pemetrexed regimens.

Results

Among 70 ALK-positive patients treated with a platinum/pemetrexed regimen, the median PFS (mPFS) was 7.3 months (95% confidence interval (CI) 5.5-9.5). The mPFS of 51 ALK-positive patients treated with single-agent pemetrexed or nonplatinum/pemetrexed combinations was 5.5 months (2.8-9.0). For ALK-negative patients, PFS on all pemetrexed-based regimens was similar to that of ALK-positive patients, except in the specific setting of first-line platinum/pemetrexed where the mPFS was only 4.2 and 5.4 months in KRAS and WT/WT/WT patients, respectively. However, among patients with a never/light-smoking history (0-10 pack-year smoking history) treated with first-line platinum/pemetrexed, there was no difference in PFS between ALK-positive and ALK-negative patients.  

Conclusions

PFS on pemetrexed or nonplatinum/pemetrexed combinations was similar in ALK-positive and ALK-negative patients. PFS on first-line platinum/pemetrexed may be prolonged in never/light-smoking patients regardless of ALK status.