Mark A. Socinski, MD

Mark A. Socinski, MD, medical oncologist and executive medical director of the AdventHealth Cancer Institute, discusses the safety profile of tepotinib (Tepmetko) that was observed in the VISION trial (NCT02864992) of patients with advanced or metastatic non–small cell lung cancer (NSCLC) with 

As of July 2020, 255 patients in the phase 2 VISION trial had received tepotinib for a median of 5.1 months. The primary end point of objective response rate as assessed by an independent review was 45.2% (95% CI, 36.0-53.6).

Grade 3 or higher adverse events (AEs) related to tepotinib were reported in 25.1% of the safety population, including 7.5% who experienced grade 3 peripheral edema, according to Socinski. Peripheral edema of any grade was observed in 138 patients (54.1%) in the safety population. Socinski notes that it is a common AE of other MET inhibitors including capmatinib (Tabrecta) and is not life-threatening but can cause discomfort for patients.

Other serious AEs included gastrointestinal (GI) toxicity, general edema, and pleural effusion, while lower-grade AEs such as nausea and diarrhea were also common. The tolerability was relatively high overall, according to Socinski. Treatment was discontinued by 27 patients (10.6%) due to treatment-related AEs.

When you look specifically at the [AEs] that one would see, the most common one was, as I mentioned previously, peripheral edema. This occurred in nearly about half the patients, but in only 8% of the patients was it grade 3. So, grade 3 would be more significant than grades 1 or 2. [There were] other things such as GI toxicity, some grade 1 to 2 nausea, some low-grade diarrhea. There were other low-grade alterations of liver function tests, and these sorts of things. They should obviously be monitored for when patients are on treatment. Overall, I think tepotinib is a relatively well-tolerated agent.

The 1 issue as I mentioned before, is this issue of peripheral edema. It's not unique to tepotinib; we see it with pretty much any 

 inhibitor. So, it really is a class effect of these agents, the rates of peripheral edema are very similar across comparing capmatinib to tepotinib. Again, I don't know that we have a good understanding of the mechanism of action, nor do we have a good understanding of the best way to manage it. And again, it's not a life-threatening AE, but it tends to be very bothersome to patients.

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Mark A. Socinski, MD, discusses the safety profile of tepotinib that was observed in the VISION trial of patients with advanced or metastatic non–small cell lung cancer with MET exon 14 skipping mutations. 

VISION Trial Shows Favorable Tolerability of Tepotinib in NSCLC

Mark A. Socinski, MD, executive medical director at the AdventHealth Cancer Institute and member of the Thoracic Oncology Program in Orlando, Florida, discusses the patient population of the trials targeting 

 exon 14 skipping mutations in non–small cell lung cancer (NSCLC).

 exon 14 skipping mutation is a biomarker that is an oncogenic driver as well as a therapeutic target for NSCLC. It occurs in 3% to 4% of patients with NSCLC, which is more frequent than other known biomarker mutations, according to Socinski.

The phase 2, single-arm VISION trial (NCT02864992) of tepotinib (Tepmetko) investigated 153 patients who had a detected 

 exon 14 skipping mutation, 66 of whom had the mutation positively identified by liquid biopsy, 60 by a tissue biopsy, and 27 by both methods. According to Socinski, the patient population of the VISION trial was similar to the overall patient population, though the study recruited less symptomatic patients with an ECOG performance score of 0 or 1. The same was true of the phase 2 GEOMETRY Mono-1 trial (NCT02414139) of capmatinib (Tabrecta), which studied both 

 amplification. The VISION trial’s patient population had a relatively high median age of 74, and 46% had a history of smoking.

Both tepotinib and capmatinib showed efficacy and safety in patients with the 

 exon 14 skipping mutation and both drugs have been approved by the FDA for use in these patients.

 exon 14 skipping population tends to be a little bit older than the average driver mutation population. It also is likely to occur in smokers as well as non-smokers, so smoking status shouldn't necessarily be a criterion for testing or not. They almost always have adenocarcinoma of the lung; however, it has also been described in squamous [histology]. It's important to be aware of that when you're deciding on who to test for and who not to test for. Again, this occurs in roughly 3% to 4% of all of lung cancer, so it tends to be more common than we might see [in], say 

 fusions, and these sorts of things. So this should definitely be on the radar screen of any practicing oncologist to make sure that adequate testing is done here.

Specifically looking at the clinical trials for both tepotinib as well as capmatinib—these trials, since you're selecting patients based on a biomarker that's a molecular alteration—I think the patients in the trials of all of these agents were relatively representative of what you would see in practice. There was nothing unusual about it. Of course, these are patients that had to have good performance status. These were ambulatory, relatively asymptomatic, or minimally symptomatic patients. So, I think both in the VISION trial as well as the [GEOMETRY mono-1] capmatinib trial, the patients that you see and the outcomes that were described in these trials should be the expected outcomes that you would see in practice, again, because these patients are chosen for the clinical trial based on a molecular alteration.

Mark A. Socinski, MD, discusses the patient population of the trials targeting MET exon 14 skipping mutations in non–small cell lung cancer. 

Characteristics of the MET Exon 14 Skipping Mutation NSCLC Population

Socinski, mentions a few adverse events, such as fatigue, skin rash, and diarrhea, but then explains that most of these are grades 1 and 2. Very few are grades 3 and 4, but Socinski urges oncologists to be aware of the different toxicities and know how to treat them.

Socinski believes this trial is significant because it presents another monotherapy, other than docetaxel, and it happens to be better in terms of overall survival.

Mark A. Socinski, MD, professor, Medicine and Cardiothoracic Surgery, director, Lung Cancer Section, Division of Hematology/Oncology, clinical associate director, Lung SPORE, co-director, UPMC Lung Cancer Center of Excellence, co-leader, UPCI Lung Cancer Program, University of Pittsburgh, discusses the adverse events, as well as the overall significance, of nivolumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC).

Mark A. Socinski, MD | Authors

Articles

VISION Trial Shows Favorable Tolerability of Tepotinib in NSCLC

Characteristics of the MET Exon 14 Skipping Mutation NSCLC Population

Adverse Events of Nivolumab in Patients With Advanced, Non-Squamous NSCLC