mOS of nearly 4 years in Tx-naïve BRAFV600E-mutant mNSCLC with combination therapy newly available in HK

13 Feb 2026
mOS of nearly 4 years in Tx-naïve BRAFV600E-mutant mNSCLC with combination therapy newly available in HK

Updated results of the phase II PHAROS study of encorafenib plus binimetinib, a BRAF plus MEK inhibitor combination that has recently become available in Hong Kong, include a median overall survival (mOS) of 47.6 months in treatment-naïve patients and 22.7 months in previously treated patients with BRAFV600E-mutant metastatic non-small-cell lung cancer (mNSCLC).

Approved in US and Europe, and now in HK

Activating BRAFV600E mutations occur in approximately 1–2 percent of patients with NSCLC. [J Clin Oncol 2025;43:3706-3713]

“The most recent January 2025 version of the European Society for Medical Oncology [ESMO] guidelines, which are very consistent with Chinese, US National Comprehensive Cancer Network [NCCN] and other national guidelines, recommend BRAFV600 status testing in patients with mNSCLC prior to making first-time treatment decisions,” said Professor Jürgen Wolf of Center for Integrated Oncology at University Hospital Cologne, Cologne, Germany, who presented the latest PHAROS trial data recently in Hong Kong. [ESMO Oncogene-Addicted Metastatic Non-Small-Cell Lung Cancer Living Guideline, v1.2 - January 2025; Guidelines of Chinese Society of Clinical Oncology for Non-Small Cell Lung Cancer 2025; NCCN Clinical Practice Guidelines in Oncology, Non-Small Cell Lung Cancer, version 3.2026] “If the mutation is identified, ESMO guidelines recommend a targeted combination of dabrafenib plus trametinib or encorafenib plus binimetinib as first-line treatment.”

BRAF inhibitors are typically used in combination with inhibitors of the downstream kinase MEK. Targeting two kinases within the same pathway achieves greater antitumour activity and prolongs progression-free survival (PFS). “The addition of a MEK inhibitor also mitigates the paradoxical activation of the MAPK pathway and associated adverse events [AEs] that can occur as a result of BRAF inhibitor monotherapy,” explained Wolf. [Future Oncology 2022;18:781-791]

The combination of encorafenib, an oral, selective, reversible BRAF kinase inhibitor, and binimetinib, an oral, ATP-uncompetitive, reversible inhibitor of MEK1 and MEK2, received regulatory US FDA and EMA approval for BRAFV600E-mutant mNSCLC on the basis of the single-arm, open-label, multicentre, phase II PHAROS study, which showed that the primary endpoint of objective response rate (ORR) by independent radiology review (IRR) was 75 and 46 percent in treatment-naïve and previously treated patients, respectively. At data cut-off on 1 April 2024, the median PFS (mPFS) by IRR in the respective subgroups was 30.2 and 9.3 months. [J Thorac Oncol 2025;20:1538-154]

The combination of encorafenib plus binimetinib was also recently approved in Hong Kong, following the updated OS analysis of the PHAROS study.

Efficacy in Tx-naïve and previously treated patients

In PHAROS, the combination of encorafenib 450 mg QD and binimetinib 45 mg BID was given to 59 treatment-naïve (median age, 68 years; female, 56 percent; Asian, 5 percent; never-smokers, 31 percent) and 39 previously treated (median age, 71 years; female, 49 percent; Asian, 10 percent; never-smokers, 28 percent) patients with BRAFV600E-mutant mNSCLC. [J Clin Oncol 2025;43:3706-3713]

At data cut-off on 14 March 2025, mPFS by IRR was 30.4 months in treatment-naïve patients and 9.3 months in those previously treated. After a median follow-up of 52.3 months in treatment-naïve patients, the median OS (mOS) was 47.6 months, with a 4-year OS probability of 49 percent. “Such efficacy has never been reported in this patient population,” commented Wolf.

“Compared with the first-line setting, the survival outcomes were definitely poorer in pretreated patients, but they still showed remarkable and clinically relevant efficacy,” he said. For patients with previously treated disease, the mOS was 22.7 months after a median follow-up of 48.2 months, corresponding to a 4-year OS probability of 31 percent.

While Wolf cautioned against drawing definitive conclusions from subgroup analyses with small patient numbers, he highlighted that the PFS and OS data were strikingly better in never-smokers vs current or former smokers. The mPFS in treatment-naïve never-smokers was 41.8 months, compared with 24.8 months in current or former smokers, and the corresponding values in previously treated patients were 9.0 vs 18.4 months. The mOS in treatment-naïve never-smokers was 61.4 months, compared with 35.7 months in current or former smokers, while in previously treated patients it was 32.2 vs 20.0 months.

Safety

Treatment-related AEs (TRAEs) of any grade and grade 3/4 occurred in 94 and 46 percent of all patients, respectively. The most common (≥30 percent) any-grade TRAEs were nausea (52 percent), diarrhoea (44 percent), fatigue (33 percent), and vomiting (30 percent). There were no new safety signals when comparing the final safety results with the primary analysis.

“The frequency of treatment-related pyrexia with encorafenib plus binimetinib was 8 percent. This is in contrast with results of the dabrafenib plus trametinib trial, where the reported frequency of pyrexia was >50 percent,” noted Wolf. [J Thorac Oncol 2022;17:103-115]

In PHAROS, TRAEs led to dose reduction of encorafenib and binimetinib in 33 percent of patients each, and permanent discontinuation in 20 percent of patients. Overall, safety was considered comparable between the two treatment line groups.

OCEAN II: Experience in China

OCEAN II is a phase II, multicentre, single-arm study investigating the efficacy, safety and pharmacokinetics of encorafenib plus binimetinib in Chinese patients with unresectable stage IV BRAFV600E-mutant mNSCLC, who are BRAF and MEK inhibitor treatment–naïve and are either previously untreated or have had one line of prior therapy in metastatic setting. [NCT05195632/W00090GE203]

Speaking recently in Hong Kong, Professor Yan Huang of the Department of Medical Oncology at Sun Yat-Sen University in Guangzhou, China, shared a case of a patient who participated in the OCEAN II study at her institution.

A 55-year-old female never-smoker presented with a left cervical mass, which was excised in August 2023. A subsequent PET-CT revealed a right lung lesion suggestive of lung cancer along with multiple lymph node (LN), hepatic and adrenal metastases. Based on the clinical context and immunohistochemistry results the patient was diagnosed with metastatic poorly differentiation lung adenocarcinoma. NGS testing reported BRAFV600E mutation.

The patient was started on encorafenib plus binimetinib in September 2023. She reported abdominal pain, rash, hand–foot syndrome, hypoalbuminaemia, elevated blood cholesterol level, alopecia, peripheral paresthesia, and pyuria, all of which were grade 1 in severity and did not require dose adjustment.

The first follow-up CT scan in November 2023 showed partial response (PR) with size decreases in the lung and liver nodules and LNs. Overall, the patient had been on encorafenib plus binimetinib for approximately 17 months and consistently demonstrated sustained PR across eight follow-up evaluations until eventually having progressive disease in February 2025.

The patient commenced second-line treatment with pemetrexed, carboplatin, tislelizumab, and bevacizumab in March 2025. The first follow-up CT scan since starting second-line therapy showed PR. “As of January 2026, the patient's condition remained stable, with an ongoing PFS2 of about 9 months,” reported Huang.