Pharma Strategy Blog

This week, Lilly received approval from the U.S. Food and Drug Administration (FDA) for the use of Alimta (pemetrexed), in combination with cisplatin, in the first-line treatment of locally-advanced and metastatic non-small cell lung cancer (NSCLC), for patients with non squamous histology. Alimta is not indicated for treatment of patients with squamous cell non-small cell lung cancer.

According to the American Cancer Society, lung cancer (small cell and non-small cell) is the second most common cancer in both men (after prostate cancer) and women (after breast cancer).  It accounts for about 15% of all new cancers. During 2008, there will be about 215,020 new cases of lung cancer (114,690 among men and 100,330 among women).

Lung cancer is by far the leading cause of cancer death among both men and women. There will be an estimated 161,840 deaths from lung cancer (90,810 among men and 71,030 among women) in 2008, accounting for around 29% of all cancer deaths. More people die of lung cancer than of colon, breast, and prostate cancers combined.

Image courtesy of Upstate.edu

Approximately 80% to 85% of lung cancers are NSCLC rather than SCLC; there are 3 subtypes of NSCLC.  The cells in these subtypes differ in size, shape, and chemical makeup when looked at under a microscope.

Squamous cell carcinoma:

About 25% to 30% of all lung cancers are squamous cell carcinomas. They are often linked to a history of smoking and tend to be found in the middle of the lungs, near a bronchus.

Adenocarcinoma:

This subtype accounts for about 40% of lung cancers. It is usually found in the outer region of lung. People with one type of adenocarcinoma, also known as bronchioloalveolar carcinoma, tend to have a better outlook (prognosis) than
those with other types of lung cancer and tend to be non-smokers.

Large-cell (undifferentiated) carcinoma:

This subtype accounts for about 10% to 15% of lung cancers. It may appear in any part of the lung. It tends to grow and spread quickly, which can make it harder to treat effectively.

Since Alimta is approved for non-squamous cell histology this means that approx. 70% of NSCLC are eligible for treatment with the drug.

Approval in first-line advanced NSCLC for non-squamous cell histology was based on a Phase III, open-label randomized study (n=1725 patients) that evaluated Alimta plus cisplatin (AC arm) versus Gemzar (gemcitabine) plus cisplatin (GC arm). Median survival was 10.3 months in the AC arm and 10.3 months in the GC arm.  Median progression-free survival (PFS) was 4.8 and 5.1 months for the AC and GC arms, respectively.  Overall response rates were 27.1% and 24.7% for the AC and GC arms, respectively.

The impact of NSCLC histology on overall survival was also determined. Clinically relevant differences in survival according to histology were observed.  In the non-squamous cell NSCLC subgroup, the median survival was 11.0 and 10.1 months in the AC and GC groups, respectively. However, in the squamous cell histology subgroup, the median survival was 9.4 versus 10.8 months in the AC and GC groups, respectively.

This unfavorable effect on overall survival associated with squamous cell histology observed with Alimta was also noted in a retrospective analysis of the single-agent trial of Alimta versus Taxotere (docetaxel) in patients with stage III/IV NSCLC after prior
chemotherapy.

Patients treated with the Alimta regimen had less hematologic toxicity, fewer blood transfusions and decreased use of growth factors compared to those treated with the GEMZAR regimen. The most common adverse reactions (incidence greater than or equal to 20%) for Alimta in combination with cisplatin included vomiting, neutropenia, leukopenia, anemia, stomatitis/pharyngitis, thrombocytopenia and constipation.

The main benefit from this trial is potentially a change in the treatment paradigm, because Alimta offers the first sign of activity of a drug in the maintenance setting in lung cancer.   Although there is not yet full survival data from this trial, there is a significant benefit in PFS.  Alimta can be administered over a prolonged period without cumulative toxicity, so it may allow the disease to be treated as a ‘chronic’ condition.  If that is found to be the case, then it represents a major step forward in the treatment of patients who have non-squamous NSCLC.