In the realm of modern oncology, Keytruda, or pembrolizumab, has emerged as a transformative force in cancer treatment. Developed by Merck & Co., this groundbreaking immunotherapy has redefined the landscape of therapeutic interventions since its approval in 2014. As the pioneer in its class to receive regulatory approval, Keytruda has initiated a compelling discourse in the competitive field of oncology. Its expanding indications, particularly in gastrointestinal cancers, mark a pivotal shift in addressing diseases that have historically presented treatment challenges. This blog delves into Keytruda's multifaceted journey, exploring its competitive dynamics, expanding applications, and its crucial role in revolutionizing cancer treatment.
How PD-1/PD-L1 Blockers Transform Cancer Treatment
PD-1/PD-L1 inhibitors play a critical role in cancer treatment by harnessing the body's immune system to combat cancer cells. Programmed death receptor 1 (PD-1) is a protein found on the surface of certain immune cells, like T cells. It acts as a checkpoint, regulating the immune response by binding to another protein called programmed death-ligand 1 (PD-L1), which can be found on both healthy and cancerous cells. The binding of PD-1 and PD-L1 suppresses the immune system, preventing immune cells from attacking cells that express PD-L1, which includes some cancer cells. This mechanism is an immune evasion strategy utilized by cancer cells to evade attack from the immune system.
PD-1/PD-L1 inhibitors, such as Keytruda (pembrolizumab), work by blocking the interaction between PD-1 and PD-L1. When PD-1 is blocked, the immune system is released from its suppression, enabling T cells to recognize and attack cancer cells. This leads to an enhanced immune response against the cancer, potentially slowing its growth or causing the cancer cells to die. By targeting this pathway, PD-1/PD-L1 inhibitors essentially release the brakes on the immune system, allowing it to recognize and attack cancer cells more effectively. This mechanism of action represents a significant advancement in cancer therapy, particularly in cancers where the immune system's response has been hindered, providing a new way to treat various types of cancer.
Navigating Competitive Dynamics and Ongoing Rivalry
As the first PD-1/PD-L1 inhibitor approved in the U.S., Keytruda made a groundbreaking entry, preceding its rival, Bristol-Myers Squibb's Opdivo. Despite its early foray, Keytruda consistently trailed in sales behind Opdivo. Recent trial results for Opdivo hint at potential changes in the competitive landscape between these two drugs, suggesting a possible shift in their long-standing rivalry in Keytruda's favor.
Figure 1: Current PD-1/PDL-1 Blockers on the Market.
Medication Name | Sales in 2022 |
Pembrolizumab (Keytruda) | over $18.4 billion |
Nivolumab (Opdivo) | $8.25 billion |
Cemiplimab (Libtayo) | $475 million |
Indications in Gastroesophageal Cancer: A Landmark Achievement
The European Commission's recent approval of pembrolizumab (Keytruda) for use alongside trastuzumab, fluoropyrimidine, and platinum-containing chemotherapy represents a critical advance in the landscape of cancer treatment. Specifically greenlit for the initial treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma expressing PD-L1 with a combined positive score of at least 1.1, this decision was fortified by compelling findings from the phase 3 KEYNOTE-811 trial (NCT03615326). The results showcased the addition of pembrolizumab to trastuzumab and chemotherapy, resulting in substantial enhancements in progression-free survival (PFS) and overall response rate (ORR) among the PD-L1–positive patient population. While the trial exhibited a trend toward improved overall survival (OS) with pembrolizumab, it fell short of statistical significance based on the planned analysis.
The double-blind KEYNOTE-811 trial, encompassing approximately 732 patients, evaluated the addition of pembrolizumab or placebo to trastuzumab and chemotherapy as first-line treatment for HER2-positive gastric or GEJ adenocarcinoma. Key endpoints included PFS and OS, with secondary measures such as ORR, duration of response (DOR), and safety. This milestone aligns with the accelerated FDA approval of pembrolizumab, underscoring its potential as a groundbreaking treatment regimen for HER2-positive gastric or GEJ adenocarcinoma, warranting further investigation in phase 3 trials.
"With today’s approval of [pembrolizumab], we’re proud that patients whose tumors express PD-L1 with a CPS [of at least] 1 and healthcare providers in the EU will have an option that includes immunotherapy for this difficult-to-treat disease." - Scot Ebbinghaus, MD, Vice President of Global Clinical Development at Merck Research Laboratories
Market Expansions and Projected Growth
Keytruda's sales for 2022, was over $18.4 billion, signify its potential within the market. The drug's increasing reliance on PD-L1 testing potentially expands its scope to patients previously unsuccessful with other treatment options, potentially elevating its prospects in the first-line setting.
A Synergistic Alliance: The Promise of Keytruda and CAR-T Therapy in Cancer Treatment
The envisioned partnership between Chimeric Antigen Receptor T-cell (CAR-T) therapy and Keytruda represents a pioneering fusion in cancer therapy. CAR-T therapy involves the modification of a patient's T cells to recognize and combat cancer cells with precision. When paired with Keytruda, which unleashes the immune system's response by blocking the PD-1/PD-L1 pathway, the resulting tandem aims to forge a more robust and targeted assault on cancer. By enhancing the body's natural immune reaction and directly targeting cancer cells through engineered T cells, this collaborative approach holds the potential to create a more resilient and comprehensive defense against various cancers. While it's in its early investigational phases, a combined therapy stands as a beacon of hope in revolutionizing cancer treatment strategies.
Diverse Applications and Future Research Endeavors
Merck's innovative exploration of Keytruda traverses diverse cancer types, showcasing its versatile therapeutic applications. This revolutionary drug has obtained approvals for various challenging cancers. It's used in multiple ways, such as in high-risk, early-stage triple-negative breast cancer for neoadjuvant and adjuvant therapy, locally recurrent or metastatic triple-negative breast cancer in conjunction with chemotherapy, and in persistent, recurrent, or metastatic cervical cancer alongside chemotherapy—either with or without bevacizumab—for patients expressing PD-L1. It's also indicated for cases where cutaneous squamous cell carcinoma cannot be treated surgically or via radiation, as well as for esophageal or gastroesophageal junction carcinoma, particularly HER2-positive cases. Head and neck cancer, melanoma, Merkel cell carcinoma, and several other cancers are included in its vast range of approvals.
Recent studies, particularly in first-line non-small cell lung cancer, combining Keytruda with Eli Lilly's Alimta and platinum doublet therapy have shown promising responses, further reinforcing its prowess in diversified cancer therapies. Keytruda continues to evolve, offering transformative outcomes in the fiercely competitive domain of cancer treatment. Its innovative strides, notably in gastric cancer treatment and its expanding portfolio, mark significant progress in the ever-evolving landscape of cancer therapy.
References:
Cancer.Net. Immunotherapy for Colorectal Cancer. https://www.cancer.net/navigating-cancer-care/how-cancer-treated/immunotherapy-and-vaccines/immunotherapy-colorectal-cancer. Accessed October 2, 2023.
Keytruda [package insert]. Merck & Co. Inc; 2023.
National Cancer Institute. Cancer Stat Facts: Melanoma of the Skin. https://seer.cancer.gov/statfacts/html/melan.html. Accessed January 3, 2023.
US Food and Drug Administration. FDA approves pembrolizumab for adults and children with TMB-H solid tumors. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors. Accessed October 5, 2023.
Pharmaceutical Technology. European Commission grants approval for Keytruda. https://www.pharmaceutical-technology.com/news/ec-approval-merck-keytruda/. Published August 30, 2023. Accessed Obtober 15, 2023.
Fierce Pharma. Top 15 Best-Selling Cancer Drugs of 2022. https://www.fiercepharma.com/special-report/special-report-top-15-best-selling-cancer-drugs-2022. Accessed October 20, 2023.
Keytruda. Non-Small Cell Lung Cancer. https://www.keytruda.com/non-small-cell-lung-cancer/. Accessed October 9, 2023.
Reuters. Merck's Keytruda Fails to Meet One Main Goal in Gastric Cancer Trial. June 20, 2023. https://www.reuters.com/business/healthcare-pharmaceuticals/mercks-keytruda-fails-meet-one-main-goal-gastric-cancer-trial-2023-06-20/
Disclaimer:
The information provided in this article is for educational and informational purposes only. It is not intended as medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider for any questions regarding a medical condition. The author and publisher of this article do not endorse or recommend any specific medical products or treatments mentioned in the text. The reader should rely on their healthcare provider's judgment and expertise in making healthcare decisions. The author and publisher shall not be responsible or liable for any errors or omissions in this article or for any actions taken based on the information provided.
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