Pathway merging: Symbolizing the switch from one ALK inhibitor to another in lung cancer treatment.

Switching ALK Inhibitors: A Lung Cancer Game Changer?

Rhea Morgan in Health & Wellness November 2025 • 5 min read.

"Discover how a seamless transition between ALK inhibitors offers hope and improved outcomes for lung cancer patients facing drug hypersensitivity."

Lung cancer, particularly non-small-cell lung cancer (NSCLC), often harbors genetic anomalies like ALK rearrangements that drive tumor growth. Alectinib has become a go-to treatment for these ALK-positive NSCLCs, demonstrating impressive results in clinical trials. However, even the most effective drugs can sometimes trigger adverse reactions, including hypersensitivity, which can complicate treatment strategies.

Hypersensitivity reactions to ALK inhibitors like alectinib are rare, but when they occur, they can be challenging to manage. These reactions, often manifesting as skin rashes, can force treatment interruptions or even discontinuation. Historically, desensitization protocols have been employed, but they require careful monitoring and aren't always suitable for every patient, especially those with severe reactions.

Now, a new approach is gaining attention: switching to an alternative ALK inhibitor. A recent case study details how a patient experiencing severe delayed hypersensitivity to alectinib was successfully transitioned to brigatinib, another ALK inhibitor. This shift not only resolved the adverse reaction but also maintained effective tumor control, opening up a new avenue for managing treatment-related complications.

The Alectinib Challenge: When Treatment Becomes the Problem

Pathway merging: Symbolizing the switch from one ALK inhibitor to another in lung cancer treatment.

Alectinib, while generally well-tolerated, can sometimes cause hypersensitivity reactions. These reactions typically manifest as skin rashes, with Grade 3 or 4 skin rashes reported in a small percentage of patients. Due to the rarity of these cases, experience in managing them has been limited, with desensitization being the primary approach.

Desensitization, however, is not without its drawbacks. It can be a lengthy process, often requiring close inpatient monitoring, and its role in delayed hypersensitivity remains controversial. This is where the case of a 49-year-old Hispanic woman offers a beacon of hope.

The Patient's Story: A non-smoking female with a history of asthma and a resected atrial myxoma was diagnosed with a left upper lobe perihilar lung nodule, mediastinal lymphadenopathy, and a large left pleural effusion. Cytology confirmed TTF1-positive pulmonary adenocarcinoma.
Initial Treatment and Progression: Initial tests revealed EGFR wild type, no ALK rearrangement (by FISH), and no ROSI fusion. The PD-L1 TPS score was 40%. The patient was initially treated with carboplatin and pemetrexed, followed by pembrolizumab upon disease progression.
Discovery of ALK Rearrangement: Subsequent NGS-based circulating tumor DNA analysis (FoundationACT) identified EML4-ALK fusion. The reason for the initial negative FISH test remains unclear, possibly due to specimen quality.
Alectinib and Hypersensitivity: The patient started alectinib at 600 mg twice daily and showed rapid improvement. However, after 10 days, she developed a non-pruritic morbilliform rash spreading across her body, accompanied by mild lip and eye swelling, and recurrent high fevers.
Diagnosis and Management: A skin biopsy revealed spongiotic and interface dermatitis with eosinophils, confirming a delayed type IV hypersensitivity. Alectinib was withheld, and oral prednisone was initiated, leading to rapid improvement.

Instead of pursuing desensitization, doctors opted to switch the patient to brigatinib after the prednisone taper. This decision proved successful as the patient tolerated brigatinib well, without any recurrence of the rash or fever. Remarkably, follow-up scans showed significant improvement in the pleural effusion and overall tumor response.

A Promising Alternative

This case highlights the potential of switching ALK inhibitors as a viable strategy for managing severe hypersensitivity reactions. By transitioning from alectinib to brigatinib, the patient not only overcame the adverse reaction but also achieved a significant and lasting anti-tumor response. This approach offers a valuable alternative to desensitization, particularly in cases where the latter may not be appropriate or feasible. As research continues, understanding the nuances of ALK inhibitor cross-reactivity and individual patient responses will be crucial in optimizing treatment strategies and improving outcomes for individuals with ALK-positive lung cancer.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.2147/lctt.s173948, Alternate LINK

Title: Hypersensitivity In Alk-Positive Lung Cancers Exposed To Alk Inhibitors: A Case Of Successful Switch To An Alternative Alk Inhibitor And Systematic Review Of The Literature

Subject: Oncology

Journal: Lung Cancer: Targets and Therapy

Publisher: Informa UK Limited

Authors: Lei Deng, Janaki Sharma, Elizabeth Ravera, Balazs Halmos, Haiying Cheng

Published: 2018-09-01

Everything You Need To Know

What is the significance of ALK rearrangements in non-small-cell lung cancer (NSCLC), and how are they typically treated?

ALK rearrangements are genetic mutations that drive tumor growth in NSCLC. The presence of ALK-positive NSCLC is often treated with ALK inhibitors like alectinib, which has demonstrated positive results in clinical trials. These inhibitors target the ALK protein, effectively inhibiting the growth and spread of cancer cells that express the ALK fusion protein.

Why is switching from alectinib to brigatinib a viable solution for hypersensitivity reactions, and what are the benefits?

Switching to brigatinib offers a solution for patients experiencing hypersensitivity to alectinib. In the case study, the patient developed a severe delayed type IV hypersensitivity to alectinib, manifested as skin rashes and fever. The transition to brigatinib resolved the adverse reaction and maintained effective tumor control. This approach avoids the drawbacks of desensitization, such as lengthy monitoring and potential ineffectiveness, offering a safer and more effective option, particularly for those with severe reactions.

What are the challenges associated with managing hypersensitivity reactions to ALK inhibitors like alectinib?

Hypersensitivity reactions to ALK inhibitors, such as alectinib, pose several challenges. These reactions, often presenting as skin rashes, can interrupt or discontinue treatment. While desensitization has been a primary management approach, it involves potential risks and is not always suitable. The rarity of these cases limits experience in managing them, making the choice of treatment crucial for maintaining patient outcomes and quality of life. The patient experienced Grade 3 or 4 skin rashes.

Can you explain the patient's journey and how the ALK rearrangement was discovered?

The patient, a non-smoker with a history of asthma, was diagnosed with lung cancer and initially tested negative for ALK rearrangement using FISH. She was treated with carboplatin, pemetrexed, and pembrolizumab. However, a subsequent NGS-based circulating tumor DNA analysis identified an EML4-ALK fusion. Upon starting alectinib, she showed improvement but developed a severe hypersensitivity reaction, confirmed by a skin biopsy. This led to switching her to brigatinib after oral prednisone, which resolved the adverse reaction and resulted in tumor response.

What does the case study suggest about the future of managing ALK-positive lung cancer treatments, and what further research is needed?

The case study indicates that switching ALK inhibitors, specifically from alectinib to brigatinib, can be a successful strategy for managing hypersensitivity reactions. It offers an alternative to desensitization, enhancing patient outcomes. For the future, it emphasizes the need for further research to understand the nuances of ALK inhibitor cross-reactivity and individual patient responses to refine treatment strategies. This will help improve the management of ALK-positive lung cancer and improve outcomes for patients, ensuring a more tailored and effective approach to treatment.