In a landmark study unveiled recently, Pfizer’s Lorbrena has shown the potential to dramatically extend the lives of patients suffering from ALK-positive lung cancer, a rare and particularly aggressive form of the disease. This revelation brings a new wave of hope to a patient demographic that, until now, has faced grim prognoses.
Lorbrena targets a subset of non-small cell lung cancers characterized by a specific genetic mutation known as ALK. While non-small cell lung cancers account for about 85% of all lung cancer cases, ALK-positive variants are rare, making up just 4% of these diagnoses—affecting over 70,000 individuals globally each year. This cancer typically strikes younger, non-smoking individuals, adding to the urgency of finding effective treatments.
One of the most alarming aspects of ALK-positive lung cancer is its propensity to metastasize to the brain. Within the first two years post-diagnosis, about 25% of patients experience brain metastasis, a rate that only increases over time. Dr. Ben Solomon, who spearheaded the Pfizer-supported study and serves as head of lung medical oncology at the Peter MacCallum Cancer Centre in Australia, highlighted the aggressive nature of this cancer and the significant threat it poses.
The recent follow-up to an earlier phase 3 clinical trial has yielded promising results. After five years, a remarkable 60% of patients treated with Lorbrena were still alive, compared to a mere 8% who were administered crizotinib, another drug by Pfizer known as Xalkori. These findings, published in the Journal of Clinical Oncology and presented at the American Society of Clinical Oncology’s annual meeting, underscore the transformative potential of Lorbrena.
Dr. John Heymach, chair of thoracic and head and neck medical oncology at MD Anderson Cancer Center, described the results as groundbreaking. “For the first time, we are seeing that most patients can go beyond five years without their cancer progressing, which is unprecedented in this field,” he stated.
However, it is worth noting that crizotinib, the drug used as a comparison in the study, is no longer a standard treatment in the U.S. Dr. Julie Gralow, chief medical officer and executive vice president at the American Society of Clinical Oncology, pointed out that while Lorbrena and crizotinib are both tyrosine kinase inhibitors, crizotinib is a first-generation drug, whereas Lorbrena (generic name lorlatinib) is a third-generation medication. Currently, the standard treatment for ALK-positive lung cancers includes Lorbrena and two second-generation drugs: brigatinib (Alunbrig) and alectinib (Alecensa).
Despite the shift in standard care, the study’s long-term data remain the most impressive seen for this class of drugs. “The progression-free survival rates are the highest we’ve observed in this patient population,” Gralow emphasized.
Another critical finding from the study was Lorbrena’s effectiveness in preventing brain metastasis. Patients on Lorbrena were 95% less likely to develop brain metastasis compared to those on crizotinib. This is a significant breakthrough, given that brain metastasis severely impacts quality of life and leads to debilitating side effects. Only four out of 114 patients on Lorbrena developed brain metastasis within approximately 16 months, compared to 39 out of 109 on crizotinib.
Dr. Heymach noted the unparalleled efficacy of Lorbrena in the brain. “Earlier drugs like crizotinib couldn’t prevent brain metastasis effectively. While alectinib and brigatinib have some brain protection capabilities, Lorbrena’s performance is unmatched,” he said.
The drug’s ability to cross the blood-brain barrier, a membrane that shields the brain from harmful substances, plays a crucial role in its effectiveness. This capability not only helps in preventing brain metastasis but also in treating existing ones, improving patients’ overall prognosis.
However, this enhanced brain penetration comes with potential side effects. Dr. Aaron Mansfield from the Mayo Clinic cautioned that patients on Lorbrena might experience more memory and mood issues than those on second-generation drugs. This neurotoxicity could be particularly challenging for patients with pre-existing psychiatric conditions. Dr. Solomon suggested that reducing the dosage could mitigate these cognitive side effects without compromising the drug’s efficacy.
Importantly, these tyrosine kinase inhibitors, including Lorbrena, are only effective in patients with the ALK-positive mutation, which occurs when two genes break and fuse together, a process sometimes referred to as ALK fusion. Dr. Isabel Preeshagul, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, stressed the need for thorough genetic testing. “Patients diagnosed with stage 4 lung cancer should insist on next-generation sequencing to determine if they have the ALK mutation. Targeted therapies like Lorbrena can be life-changing,” she advised.
The journey to find the most effective treatment for ALK-positive lung cancer is ongoing. While Lorbrena represents a significant leap forward, comparative trials involving all current standard-of-care drugs are essential to determine the ultimate best-in-class therapy. Until then, Lorbrena stands as a beacon of hope, offering extended survival and improved quality of life for those battling this formidable disease.
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Source: NBC News