, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, 

covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, sponsored by Real Chemistry, we had the pleasure of speaking with Paul K. Paik, MD, about the use of tepotinib (Tepmetko) in patients with non–small cell lung cancer (NSCLC) harboring 

 exon 14 skipping alterations. Dr Paik is the clinical director of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center in New York, New York.

In our exclusive interview, Dr Paik discussed key findings from the phase 2 VISION trial (NCT02864992) investigating frontline tepotinib in patients with NSCLC harboring 

 exon 14 skipping alterations, real-world data from the TOGETHER pooled analysis of tepotinib vs other frontline treatment options in this patient population, and insights regarding treatment sequencing with tepotinib in pretreated patients in this population.

That’s all we have for today! Thank you for listening to this episode of 

, sponsored by Real Chemistry. Check back on Mondays and Thursdays for exclusive interviews with leading experts in the oncology field.

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Podcasts

Dr Paik discusses the VISION trial of tepotinib in NSCLC harboring MET exon 14 skipping alterations and real-world data from the TOGETHER pooled analysis.

Paik Provides Insights Into Tepotinib Treatment in NSCLC Harboring MET Exon 14 Skipping Alterations

Dr Paik on the Full FDA Approval of Tepotinib for mNSCLC Harboring MET Exon 14 Skipping Alterations

Paul K. Paik, MD, clinical director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the significance of the FDA approval of tepotinib (Tepmetko) for patients with metastatic non–small cell lung cancer (mNSCLC) harboring 

the FDA granted full approval to tepotinib

 for the treatment of adult patients with mNSCLC harboring 

 exon 14 skipping alterations. This regulatory decision follows the 

 in 2021 for this indication based on initial findings from the single-arm, phase 2 VISION trial (NCT02864992).

The full approval of tepotinib for this population validates the initial accelerated approval, Paik says. In the initial readout of the trial, treatment with tepotinib led to an overall response rate (ORR) of 43% (95% CI, 32%-56%) among 69 previously untreated patients. The FDA’s conversion to a full approval was supported by data from an additional 161 patients enrolled in VISION, which is one of the largest prospective clinical trials investigating a MET inhibitor in patients with mNSCLC harboring 

 exon 14 skipping alterations, having enrolled 313 patients, Paik explains. With 28 months of additional follow-up, the efficacy with tepotinib has increased, Paik emphasizes. Tepotinib generated an ORR of 57% (95% CI, 49%-65%) in evaluable treatment-naive patients (n = 164) and 45% (95% CI, 37%-53%) in evaluable previously treated patients (n = 149).

Furthermore, the median progression-free survival (PFS) and overall survival (OS) data with tepotinib have matured and look promising, Paik adds. In the overall population, the median PFS was 11.2 months (95% CI, 9.5-13.8), and the median OS was 19.6 months (95% CI, 16.2-22.9). In previously untreated patients, these median values were 12.6 months (95% CI, 9.7-17.7) and 21.3 months (95% CI, 14.2-25.9), respectively. In previously treated patients, these respective median values were 11.0 months (95% CI, 8.2-13.7) and 19.3 (95% CI, 15.6-22.3).

Clinicians referring a patient to MSK can do so by visiting 

, emailing referapatient@mskcc.org, or by calling 833-315-2722.

Videos

Paul K. Paik, MD, discusses the FDA approval of tepotinib for metastatic non–small cell lung cancer harboring MET exon 14 skipping alterations.

Paul K. Paik, MD, associate attending physician, clinical director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, discussed using tepotinib — a highly selective, ATP-competitive, reversible, potent MET TKI – to treat patients with non–small cell lung cancer (NSCLC) with 

 mutations are reported in approximately 3% to 4% of patients with NSCLC. In the phase II VISION study, 85 patients were enrolled and had detected METex14 mutations, 55 were detected using liquid biopsies, and 52 were detected using tumor biopsies. Patients received 500 mg of tepotinib daily until progression, intolerable toxicity, or withdrawal. In evaluable liquid biopsy patients, the objective response rate (ORR) was 50% by independent central review (IRC) and 55.3% by investigator assessment. In 51 evaluable tumor biopsy patients, ORR was 45.1% by IRC and 54.9% by investigator assessment.

Any grade treatment-related adverse events (TRAEs), reported by ≥10% of 69 patients evaluable for safety, included peripheral edema (48.3%), nausea (23.0%), diarrhea (20.7%), blood creatinine increased (12.6%), and asthenia (9.2%). No TRAEs were grade 4 or 5. No TRAEs led to death but led to permanent discontinuation in 4 patients.

Tepotinib showed durable clinical activity in patients with NSCLC and 

 mutations and had a favorable safety profile. Recruitment for this trial is ongoing.

Paul K. Paik, MD, discussed using tepotinib&mdash;a highly selective, ATP-competitive, reversible, potent MET TKI&mdash;to treat patients with non–small cell lung cancer with MET exon 14 skipping mutations.

Dr. Paik on Tepotinib in METex14-Mutated NSCLC

Paul K. Paik, MD, clinical director of the Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, discusses how the potential approval of lorlatinib may alter the landscape for patients with 

-positive non—small cell lung cancer (NSCLC).

Although the data with lorlatinib remain unclear, the potential approval of this agent will give physicians a new tool to use, says Paik. As long as there is a rational approach to this—based on how the patient is doing and what the molecular biology is with additional testing&mdash;it is certainly a reasonable approach in the post-alectinib (Alecensa) setting, he adds.

Other options should and can be considered, says Paik. One option is ALK inhibitors, particularly if the mutation-specific data warn against lorlatinib use. Another treatment option to consider is chemotherapy. Chemotherapy is still a very good option for these patients and should definitely be considered for treatment, particularly if a physician needs something reliable to get a patient over their symptoms, says Paik.

Paul K. Paik, MD, clinical director of the Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, discusses how the potential approval of lorlatinib may alter the landscape for patients with ALK-positive non–small cell lung cancer (NSCLC).

Dr. Paik on the Potential Approval of Lorlatinib for Patients With ALK-Positive NSCLC

Paul K. Paik, MD, clinical director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, discusses resistance mutations in patients with non—small cell lung cancer (NSCLC).

 at the end of 2016 showed that a patient with 

-positive lung cancer who had received crizotinib (Xalkori) developed disease progression. As is recommended, the tumor was biopsied and physicians found a particular alteration that should have predicted sensitivity to lorlatinib. The patient was treated with lorlatinib and had a very good response.

Over time, the patient developed another resistance mutation. The particular mutation predicted sensitivity to crizotinib, which was the drug the patient had originally progressed on. The patient received the drug and showed a dramatic response in the patient’s liver metastases. The use of preclinical data and importing it directly into clinical practice does work, states Paik.

Paul K. Paik, MD, clinical director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, discusses resistance mutations in patients with non–small cell lung cancer (NSCLC).

Dr. Paik on Resistance Mutations in NSCLC

Paul K. Paik, MD, clinical director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, discusses recent advancements in squamous cell lung cancer.

The biggest recent advancement in the treatment of squamous cell lung cancer is immunotherapy, says Paik. In 2015, the CheckMate-017 trial led to the first approval of immunotherapy in lung cancer.

In the wake of immunotherapy, excitement for chemotherapy options has lessened, adds Paik.

Paul K. Paik, MD, clinical director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, discusses recent advancements in squamous cell lung cancer.
 

Paul K. Paik, MD

Articles

Paik Provides Insights Into Tepotinib Treatment in NSCLC Harboring MET Exon 14 Skipping Alterations

Dr Paik on the Full FDA Approval of Tepotinib for mNSCLC Harboring MET Exon 14 Skipping Alterations

Dr. Paik on Tepotinib in METex14-Mutated NSCLC

Dr. Paik on the Potential Approval of Lorlatinib for Patients With ALK-Positive NSCLC

Dr. Paik on Resistance Mutations in NSCLC

Dr. Paik Discusses Advances in Squamous Cell Lung Cancer