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Targeting KRAS Mutations in Advanced NSCLC: Early Trial Results

By: Lauren Harrison, MS
Posted: Tuesday, December 8, 2020

Combination therapy using cisplatin, pemetrexed, and the selective MEK inhibitor binimetinib for non–small cell lung cancer (NSCLC) with mutations in KRAS is thought to be safe; however, no early signal of increased efficacy with binimetinib was seen. Patrizia Froesch, MD, of the Oncology Institute of Southern Switzerland in Bellinzona, presented the findings of this phase Ib trial on behalf of her colleagues at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 (Abstract 557P).

Researchers recruited 18 patients with stage III or IV NSCLC who were not suited for curative treatment. No patients had received prior systemic therapy, and all had mutations in KRAS exons 2 or 3. A total of 13 patients were enrolled into part 1 of the study, which had a 3+3 design plus dose escalation using two dose levels of binimetinib; 5 patients were enrolled in part 2, which was an expansion cohort at the maximum tolerated dose of binimetinib. Patients were treated with four cycles of 75 mg/m2 of cisplatin, 500 mg/m2 of pemetrexed, plus 30 mg (dose level 1) or 40 mg (dose level 2) of twice daily binimetinib every 3 weeks. These cycles were followed by pemetrexed and binimetinib until progressive disease or unacceptable toxicity.

The overall response rate was 33%, with a median progression-free survival of 5.7 months. The median overall survival was 6.5 months. In the first part of the study, nine patients (three at dose level 1, six at dose level 2) were evaluated for dose-limiting toxicities, and none were seen after a median of two cycles. All patients are currently off treatment, mostly due to progressive disease (30%) and patient/physician decision (30%).

There were no grade 4 or 5 adverse events recorded throughout the study. However, common treatment-related grade 3 adverse events were fatigue, nausea, anemia, hypertension, and lung infection. One grade 3 thromboembolic event was noted as well.

Disclosure: For a full list of authors’ disclosures, visit oncologypro.esmo.org.



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