Pfizer Produces Promising Advances in ALK-Positive Lung Cancer Treatment

Lung cancer remains the most frequently diagnosed cancer globally, responsible for one in eight cancer cases. Despite advancements in surgery, chemotherapy, radiation therapy, and immunotherapy, survival rates for patients with advanced lung cancer have historically been poor. However, a new drug from Pfizer, Lorbrena (lorlatinib), is showing significant promise, particularly for patients with ALK-positive non-small cell lung cancer (NSCLC).

Breakthrough Clinical Trial Results

Lorbrena has demonstrated remarkable efficacy in halting the progression of ALK-positive NSCLC, a form of lung cancer driven by mutations in the ALK gene that lead to abnormal lung cell growth. In Pfizer’s CROWN trial, which included 296 patients, Lorbrena reduced the risk of intracranial progression—a stage where tumors form in the brain—by 94%. This represents the longest progression-free survival ever recorded for NSCLC patients.

Dr. Todd Bauer, a medical oncologist with Tennessee Oncology, shared that after a five-year follow-up, 60% of patients on Lorbrena continued to benefit from the treatment without reaching a median progression-free survival point. This unprecedented outcome underscores Lorbrena’s potential in transforming the prognosis for ALK-positive NSCLC patients.

Comparative Efficacy and Side Effects

Lorbrena is the first ALK tyrosine kinase inhibitor (TKI) to report five-year progression-free survival. Unlike earlier inhibitors like Xalkori (crizotinib), which typically lose effectiveness after 12 months due to drug resistance and cancer mutations, Lorbrena continues to provide long-term benefits.

Common side effects of Lorbrena include hypercholesterolemia (high cholesterol) and hypertriglyceridemia (high triglycerides), which can be managed with statins and fibrates. Other side effects such as edema, numbness, weight gain, cognitive issues, fatigue, and joint pain can often be mitigated through lifestyle modifications or dose adjustments. Importantly, dose reductions have not been shown to compromise the drug’s efficacy.

Protection Against Brain Metastases

Brain metastases are a significant concern for lung cancer patients, occurring in about 25% of cases at diagnosis and generally leading to poor outcomes. The CROWN trial revealed that 92% of patients on Lorbrena had not developed brain cancer after five years, compared to just 21% of those on Xalkori. For patients with existing brain metastases, 81% on Lorbrena saw no further progression, whereas all patients on Xalkori experienced progression or dropped out of the study within two years.

Candidates for Lorbrena

Lorbrena is currently approved in the U.S. for adults with ALK-positive NSCLC, as confirmed by an FDA-approved test on a tissue sample. While ALK-positive NSCLC accounts for only 5% of all NSCLC cases, the aggressive nature of this cancer type necessitates effective treatment options like Lorbrena. Additionally, other genetic markers, such as mutations in the TP53 gene, may also influence treatment response.

Improving Lung Cancer Survival Rates

The development of drugs like Lorbrena contributes to the ongoing improvement in lung cancer survival rates. Recent statistics indicate a positive trend, with the overall five-year survival rate for lung cancer increasing from 16% in the early 2000s to 21.7% as of 2021. These advancements reflect the impact of targeted therapies and improved treatment protocols.