According to independent review, the median duration of response was 11.1 months (95% CI, 7.2-could not be estimated) in the combined-biopsy group, 9.9 months (95% CI, 7.2-could not be estimated) in the liquid-biopsy group, and 15.7 months (95% CI, 9.7-could not be estimated) in the tissue-biopsy group. The results of investigator review were similar.

Independent review also found that the median duration of progression-free survival was 8.5 months (95% CI, 6.7-11.0) in the combined-biopsy group, 8.5 months (95% CI, 5.1-11.0) in the liquid-biopsy group, and 11 months (95% CI, 5.7-17.1) in the tissue-biopsy group, and investigator review found similar results.

At data cutoff, 27 of 77 patients (35%) who had stopped receiving tepotinib were given subsequent treatment. Median overall survival was 17.1 months (95% CI, 12-26.8) according to data that were not yet mature.

Independent review determined that among the 11 patients with brain metastases, the response rate was 55% (95% CI, 23-83), and the median duration of response was 9.5 months (95% CI, 6.6-could not be estimated). In this group of patients, the median progression-free survival was 10.9 months (95% CI, 8-could not be estimated).


Continue Reading

In the safety population of 152 patients, 98% experienced adverse events while receiving treatment. Adverse events that were thought to be related to tepotinib were reported by 89% of the patients. Of the patients in the safety population, 28% experienced adverse events of grade 3 or higher, with peripheral edema being the most common such adverse event.

Serious adverse events related to tepotinib were reported by 15% of the patients. Moreover, 21 patients reported adverse events that led to death while they were being treated with tepotinib. The researchers determined the death of patient aged 79 years with respiratory failure and dyspnea, secondary to interstitial lung disease, was linked to tepotinib.

Mark Socinski, MD, the executive medical director of the Advent Health Cancer Institute in Orlando, Florida, who was not involved in the new study, said that the new research underscores the importance of comprehensive molecular testing in patients with NSCLC. “There isn’t a patient in the country [with the condition] that shouldn’t have comprehensive molecular testing done,” he said. “And I would argue that it should be done on tissue as well as blood, because we do have the technology to do blood-based testing at the current time. And that should be part of the package as far as I’m concerned.”

Razelle Kurzrock, MD, distinguished professor of medicine at the University of California San Diego School of Medicine, California, who was not involved in the new study, said she was impressed with the new findings. Dr Kurzrock said that she had conducted an early-phase study of tepotinib in patients with advanced solid tumors and found it was “extremely well tolerated.” She also stressed the value of conducting next-generation sequencing in patients with lung cancer. “I think that it really needs to be done for every patient, and the reason is because we now have so many targetable alterations in lung cancer,” she said. Even though individual alterations may occur in small subsets of patients, these numbers add up.  Dr Kurzrock estimated as many as 1 in 3 patients with lung cancer might have alterations that could be targeted with a recently developed drug.

Gerald S. Falchook, MD, MS, director of drug development at Sarah Cannon Research Institute at HealthONE in Denver, Colorado, who was not involved in the new study, said he was impressed that the authors were able to find the patients eligible for the trial—because as noted, the alterations that the investigators focused on are only found in about 3% to 4% of patients with lung cancer. “It is quite a bit of effort to identify these patients, but it’s definitely worth the effort, as you can see with the high response rate among patients treated on this trial,” he said.

Disclosures: Some authors have received honoraria or research funding from the pharmaceutical industry. Please refer to the original paper for a full list of disclosures.

References

  1. Falchook GS, Kurzrock R, Amin HM, et al. First-in-man phase I trial of the selective MET inhibitor tepotinib in patients with advanced solid tumors. Clin Cancer Res 2020;26:1237-1246. doi:10.1158/1078-0432.CCR-19-2860
  2. Paik PK, Felip E, Veillon R, et al. Tepotinib in non-small-cell lung cancer with MET Exon 14 skipping mutations. N Engl J Med. 2020;383(10):931-943. doi:10.1056/NEJMoa2004407