Benjamin Besse, MD, head of the Department of Cancer Medicine at Institut Gustave Roussy, discusses the results of an ad-hoc safety analysis of the phase 1/2 LIBRETTO-001 trial (NCT03157128), which examined the use of selpercatinib (Retevmo) in patients with 

-altered advanced medullary thyroid cancer and non–small cell lung cancer (NSCLC).

Most of the adverse effects (AEs) associated with selpercatinib are manageable, according to Besse. At the 

, updated data on the toxicities experienced by patients who received treatment with selpercatinib were presented. In total, 702 patients were enrolled to the trial, a majority of whom had NSCLC or medullary thyroid cancer.

AEs were found to be dose dependent, with patients experiencing any grade of dry mouth (38.9%), diarrhea (36.6%), hypertension (35.9%), fatigue (35.0%), edema (34.5%), and liver toxicities (Aspartate aminotransferase increase, 29.9%; Alanine transaminase increase, 28.6%). However, 6.9% of patients discontinued after less than 12 months of treatment with selpercatinib and 2.1% discontinued after 12 months or more because of treatment emergent AEs, Besse notes. Additionally, reducing the dose of the agent helped decrease toxicities in this patient population, Besse concludes.

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Benjamin Besse, MD, discusses the results of an ad-hoc safety analysis of the phase 1/2 LIBRETTO-001 trial, which examined the use of selpercatinib in patients with RET-altered advanced medullary thyroid cancer and non–small cell lung cancer.

Dr. Besse on the Safety of Selpercatinib in Advanced RET+ Thyroid Cancer, NSCLC

Benjamin Besse, MD, Institut Gustave Roussy, Villejuif, Paris Sud University, discusses the combination of necitumumab (Portrazza) and abemaciclib (Verzenio) in patients with stage IV non—small cell lung cancer (NSCLC).

Findings from a phase Ib study showed that this combination failed to improve outcomes in this patient population. The 2-part, single-arm trial with an expansion cohort was designed to evaluate the safety and efficacy of the combination in comparison with historical data. Median progression-free survival (PFS) was 2.14 months (95% CI, 1.41-2.76) and median overall survival (OS) was 6.93 months (CI 95%, 4.96-12.85). The PFS rate at 3 months was 32.3% and 22.2% at 6 months. At 6 months, OS was 57.3%.

The activity of the combination was not as elevated as expected, says Besse, and the trial was considered negative. When compared with single-agent erlotinib (Tarceva) in non-driver NSCLC, the activity is quite similar, Besse explained. The combination should not be developed further unless a predictive biomarker for necitumumab or abemaciclib can be found. If a biomarker is defined, this combination could be revisited in a molecularly selected population, Besse concludes.

Benjamin Besse, MD, Institut Gustave Roussy, Villejuif, Paris Sud University, discusses the combination of necitumumab (Portrazza) and abemaciclib (Verzenio) in patients with stage IV non–small cell lung cancer.

Dr. Besse on Combination of Necitumumab and Abemaciclib in NSCLC

Benjamin Besse, MD, Institut Gustave Roussy, Villejuif, Paris Sud University, discusses challenges facing the treatment of patients with stage IV non—small cell lung cancer (NSCLC).

One of the current challenges of patients with stage IV NSCLC is the options for treatment in third-line setting, Besse says in an interview during the 2018 European Lung Cancer Congress, which is a joint collaboration between ESMO and the IASLC. Currently, there are 2 lines of chemotherapy and immunotherapy. However, in the third-line setting, there are no approved agents but erlotinib (Tarceva), which has poor activity in unselected populations.

Necitumumab (Portrazza), an antibody that targets EGFR, is approved in the first-line setting in combination with cisplatin and gemcitabine for patients with squamous NSCLC. Since this combination has activity, necitumumab is being investigated in combination with abemaciclib (Verzenio) as there is some biological rationale for combining those 2 drugs, Besse explains.

Benjamin Besse, MD, Institut Gustave Roussy, Villejuif, Paris Sud University, discusses challenges facing the treatment of patients with stage IV non

Dr. Besse Discusses Challenges Facing Stage IV NSCLC

Benjamin Besse, MD, Institut Gustave Roussy, Villejuif, Paris Sud University, discusses the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) for patients with non—small cell lung cancer.

One percent of patients with NSCLC have the BRAF V600E mutation. This mutation is highly predictive of the combination of dabrafenib and trametinib. Both have been proven to be highly effective in pretreated patients with NSCLC with a response rate of 60% and a progression-free survival of 10 months.

It is a potent combination that has the potential to be the standard of care. These drugs alone are quite toxic but together the toxicity is much less, explains Besse.

Benjamin Besse, MD, Institut Gustave Roussy, Villejuif, Paris Sud University, discusses the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) for patients with non

Benjamin Besse, MD

Articles

Dr. Besse on the Safety of Selpercatinib in Advanced RET+ Thyroid Cancer, NSCLC

Dr. Besse on Combination of Necitumumab and Abemaciclib in NSCLC

Dr. Besse Discusses Challenges Facing Stage IV NSCLC

Dr. Besse on the Combination of Treatments for NSCLC