Episode 19 - Rigosertib in RDEB cutaneous SCC

In this episode of BJD Talks, Sam and Meera discuss the article ‘Efficacy and safety of rigosertib in patients with recessive dystrophic epidermolysis bullosa-associated advanced/metastatic cutaneous squamous cell carcinoma’ by Laimer et al. The full article can be accessed at https://doi.org/10.1093/bjd/ljaf205 

*This podcast was generated by an AI tool created by 67Bricks for the British Association of Dermatologists* 

Transcript

SPEAKER_01 0:00

Welcome to BJD Talks, the official podcast of the BJD. I'm Sam.

SPEAKER_00 0:04

And I'm Mira. In this episode, we will be discussing the article by Martin Lehmer et al. Efficacy and Safety of Rigor Certib in Patients with a recessive dystrophic epidermolysis, bellosa, associated advanced and metastatic cutaneous squamous cell carcinoma, published in May 2025 and included in the October 2025 issue.

SPEAKER_01 0:28

RDEB is one of those rare yet devastating conditions that dermatologists and researchers are continuously trying to better understand and treat. What caught my eye here was the focus on a therapeutic option for its deadliest complication, those aggressive squamous cell carcinomas.

SPEAKER_00 0:44

Exactly. For context, RDEB is caused by mutations in the COS7A1 gene, disrupting type 7 collagen. Patients develop fragile skin, prone to blistering and scarring. Tragically, many develop highly aggressive cutaneous squamous cell carcinomas. These are distinct with a median onset age of 29.5 years and survival of only 2.4 years once diagnosed.

SPEAKER_01 1:10

Which makes this study so important. The researchers evaluated rigorcertib, a multikinase inhibitor, as a potential treatment option using two investigator-led phase two trials in Europe and the US. The cohort was small, just five patients. But the findings are intriguing.

SPEAKER_00 1:28

They are. Patients received rigasertib either intravenously or orally, according to their needs. Over the 12-month study, four of the five patients who completed more than one treatment cycle showed clinical responses. Remarkably, two achieved complete remission.

SPEAKER_01 1:44

That is extraordinary given the aggressive nature of RDEB associated SCC. The researchers identified the drug on its ability to inhibit PLK1, a protein crucial for cell cycle regulation, targeting multiple cancer-promoting pathways. For patients failing standard treatments like surgery or immunotherapy, this represents real progress.

SPEAKER_00 2:08

It does, but the study isn't without limitations. The sample size was very small, just five patients, and results varied by dose and administration method. Intravenous therapy appeared to offer better systemic availability, which could be significant.

SPEAKER_01 2:24

Safety is another consideration. Adverse events like non-infective cystitis, hematuria, and urinary urgency were common, requiring dose adjustments. These could complicate broader use in larger patient groups.

SPEAKER_00 2:37

Indeed, chronic inflammation and scarring in RDEB likely impact tumour behaviour too, making assessments complex. Using recessed and EORTC criteria alongside clinical evaluations here was helpful, but future trials must account for such challenges.

SPEAKER_01 2:54

Even so, some outcomes were remarkable. One patient achieved complete tumour remission within 12 weeks, though they later experienced local recurrence. Sustained remission like this is almost unheard of in this setting.

SPEAKER_00 3:08

Absolutely. Another patient remained tumour-free after six cycles and even reported improved quality of life. This hints at rigorcertib's potential not just to prolong life but also to enhance it, a critical goal for treating this condition.

SPEAKER_01 3:23

So, where does this leave us? Riguscertib offers hope in cases where no approved therapies exist. Its flexibility in being administered either intravenously or orally is also advantageous given the specific challenges RDEB patients face.

SPEAKER_00 3:38

It feels like a promising start. Larger, possibly multi-centred trials could build on this. There's also potential for exploring rigoscertib as neoadjuvant therapy or to delay amputations in these patients.

SPEAKER_01 3:51

Agreed. While these findings are early, they provide a foundation for further research. For patients with devastating odds, studies like this offer a much needed glimmer of hope.

SPEAKER_00 4:01

Absolutely. Thanks for listening to this episode of BJD Talks. Let us know your thoughts on today's discussion. Reach out and let's keep the conversation going.