# Case Report: Lorlatinib for the treatment of ALK-rearranged poorly differentiated thyroid carcinoma after progression to prior ALK-specific tyrosine-kinase inhibitor

## TL;DR

A patient with a rare aggressive thyroid cancer showed long-term remission after switching to a third-generation drug when initial treatment failed.

## Contribution

Demonstrates the effectiveness of sequential ALK inhibition in overcoming resistance in ALK-rearranged thyroid cancer.

## Key findings

- A patient with ALK-rearranged PDTC achieved a complete metabolic response with ceritinib.
- Lorlatinib induced a durable complete metabolic response lasting over four years with minimal toxicity.
- Sequential ALK inhibition may overcome resistance in ALK-rearranged thyroid cancer.

## Abstract

ALK rearrangements are rare but actionable oncogenic drivers in thyroid cancer, particularly in aggressive histologies such as poorly differentiated thyroid carcinoma (PDTC), and evidence supporting sequential ALK inhibition in this setting is scarce. We report a 19-year-old male with ALK-rearranged, radioiodine-refractory PDTC who started systemic therapy with ceritinib, achieving a complete metabolic response. After treatment discontinuation and subsequent progression despite ceritinib reintroduction, lorlatinib was initiated. Treatment with the third-generation ALK inhibitor led to a deep and durable complete metabolic response, sustained for more than four years, including persistence of remission after treatment discontinuation, with minimal toxicity. This case highlights the potential role of sequential ALK inhibition to overcome acquired resistance in ALK-rearranged TC and underscores the importance of comprehensive molecular profiling to guide personalized treatment strategies in rare aggressive thyroid cancers.