ESTRO 2023

Session Item

Sarcoma/Skin cancer/malignant melanoma

Session Code: 6022

Session Type: Poster (Digital)

Track: Clinical

RT after Encorafenib and Binimetinib on BRAF mutated melanoma brain metastases. GEM1802-Phase II

Ana Alvarez, Spain

Presentation Number: PO-1557

Abstract

Abstract Title:

RT after Encorafenib and Binimetinib on BRAF mutated melanoma brain metastases. GEM1802-Phase II

Authors:

Ana Alvarez¹, Izascun Valduvieco², Ana Arance³, Raquel Delgado⁴, Miguel Angel Berciano⁵, Fernando López Campos⁶, Ainara Soria⁷, Jose Luis Romero⁸, Pedro Sánchez Mauriño⁹, Anna Lucas¹⁰, Juan Martín Liberal¹¹, Pedro José Prada¹², Almudena García Castaño¹³, Maria Carmen Alamo¹⁴, Enrique Puertas¹⁵, María González Cao¹⁶, Antonio Conde¹⁷, Roberto Díaz Beveridge¹⁸, Juan Antonio Corona¹⁹, Carlos Aguado²⁰, Palmira Foro²¹, Joana Vidal²², Francisco López Soler²³, Pablo Cerezuela Fuentes²⁴, Iván Márquez Rodas²⁵

¹HGU Gregorio Marañón, Radiation Oncology, Madrid, Spain; ²H Clinic, Radiation Oncology, Barcelona, Spain; ³H Clinic, Medical Oncology, Barcelona, Spain; ⁴H Regional de Málaga, Radiation Oncology, Malaga, Spain; ⁵Unidad de Gestión Intercentros. H U Regional y Virgen de la Victoria. IBIMA., Medical Oncology, Málaga, Spain; ⁶H. Ramón y Cajal, Radiation Oncology, Madrid, Spain; ⁷H Ramón y Cajal, Medical Oncology, Madrid, Spain; ⁸HU Reina Sofía, Radiation Oncology, Córdoba, Spain; ⁹HU Reina Sofía, Medical Oncology, Córdoba, Spain; ¹⁰ICO L´Hospitalet, Radiation Oncology, Barcelona, Spain; ¹¹ICO L´Hospitalet, Medical Oncology, Barcelona, Spain; ¹²H Valdecilla, Radiation Oncology, Santander, Spain; ¹³H Valdecilla, Medical Oncology, Santander, Spain; ¹⁴HU Virgen de la Macarena, Medical Oncology, Sevilla, Spain; ¹⁵HU Dexeus, Radiation Oncology, Barcelona, Spain; ¹⁶HU Dexeus, Medical Oncology, Barcelona, Spain; ¹⁷H la Fe, Radiation Oncology, Valencia, Spain; ¹⁸H la Fe, Medical Oncology, Valencia, Spain; ¹⁹H Clínico San Carlos, Radiation Oncology, Madrid, Spain; ²⁰H Clínico San Carlos, Medical Oncology, Madrid, Spain; ²¹H del Mar, Radiation Oncology, Barcelona, Spain; ²²H del Mar, Medical Oncology, Barcelona, Spain; ²³HCU Virgen de la Arrixaca, IMIB, Radiation Oncology, Murcia, Spain; ²⁴HCU Virgen de la Arrixaca, IMIB, Medical Oncology, Murcia, Spain; ²⁵HGU Gregorio Marañón, Medical Oncology, Madrid, Spain

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Purpose or Objective

Encorafenib and binimetinib (EB) have shown intracranial activity in patients with BRAF mutated melanoma and brain metastases (BM). Since targeted therapy responses seem to be shorter than immunotherapy, we explore the role of radiation therapy (RT) after 2 months of EB treatment as a potential way to improve the duration of response.

Material and Methods

GEM1802 was a prospective phase II clinical trial (NCT03898908) that evaluated EB (450 mg pd E + 45 mg bd B) in patients (p) with BM during 56 days (d) followed by brain RT (local or WBRT) and EB until disease progression. Two cohorts were planned: C1 (N=48), asymptomatic; and C2, symptomatic p (N=15). Primary endpoint was intracranial response rate (icRR) after 56d of EB, before RT in C1. RT was planned only in cases of partial response (PR) or stabilization (SD). In case of complete response (CR), it was omitted until progression.

Results

We report preliminary results first 47 pts, 42 of them were evaluable for RT (27p C1/15p C2). Median Follow-up 12.3 m (9.5-16.1). Primary endpoint icRR before RT was 66,7% in C1 (73.3% in C2). No patient progressed during EB.
30 p received RT (1p CR, 8p PR and 6p SD), and 12 p (4p CR, 6p PR and 2p SD) did not. RT consisted on local treatment in 15p (12 C1 and 3 C2) and WBRT in 15p (8 C1 and 7 C2). There were no differences in the main prognostic factors according to RT treatment (yes/no), except for gender distribution (92% females in Non-RT vs 37% RT, p 0.002).
Estimated IPFS (intracranial progression-free survival) at 12m was 21,46% vs 41,67 % for RT yes/no respectively (p 0.469), both groups with similar median (8.26 m vs 7.37 m).
Patients in C2 that did not achieve intracranial complete response and received RT had a numerically longer duration of response than those that did not received (Table 1).
Table1. Duration of response (median months-95% CI, descriptive analysis):

There was no significant increase in toxicity with the addition of RT.
Overall Last status: 27p (64.3%) have died (15p-55.6% C1 and 12p-80% C2), 23 of them had received RT (76.7%).

Conclusion

In this preliminary analysis, encorafenib and binimetinib showed intracranial activity in patients with BRAF brain metastases of melanoma similar to other targeted therapies. Radiation therapy could increase the duration of response only in symptomatic patients, especially if local techniques are used, although this observation should be tested prospectively.