Targeted drug found effective in patients who have lung cancer with
certain mutations

Date:
September 8, 2020
Source:
Massachusetts General Hospital
Summary:
A targeted therapy called capmatinib can provide significant
benefits to patients who have advanced lung cancer with specific
gene mutations, according to recently published results from a
phase two clinical trial.



FULL STORY ==========================================================================
A targeted therapy called capmatinib can provide significant benefits to patients who have advanced lung cancer with specific gene mutations,
according to recently published results from a phase two clinical
trial. The trial, which is published in the New England Journal of
Medicine, was conducted by an international team led by investigators
at Massachusetts General Hospital (MGH).


==========================================================================
A protein called MET affects a wide range of processes within cells,
and alterations that activate the MET gene, which codes for this protein,
have been implicated in many cancers. MET can be activated by a variety
of mechanisms.

Multiples copies of the MET gene, called MET amplification, occurs
in one-to- six percent of patients with non-small-cell lung cancer
(NSCLC). MET exon 14 skipping mutations, which cause deletion of a
region called exon 14 in the expressed protein, occur in approximately three-to-four percent of patients with NSCLC and are associated with a
poor prognosis.

The drug capmatinib is a highly potent and selective inhibitor of MET. Now researchers report results from the phase 2 GEOMETRY mono-1 study, which investigated the activity of capmatinib in 364 patients with advanced
NSCLC with MET exon 14 skipping mutations or MET amplification. Results
from this study were the basis for the US Food and Drug Administration's
May 2020 approval of capmatinib for the treatment of NSCLC patients with
MET exon 14 skipping.

In patients with MET exon 14 skipping mutations, capmatinib had a
very high response rate (68 percent) when used as the first line of
treatment, and an excellent response rate (41 percent) when used after
patients had been treated with other therapies such as chemotherapy and immunotherapy. Among patients with MET amplification with at least 10
copies of the gene, capmatinib had a response rate of 40 percent when
used as a first-line treatment and a response rate of 29 percent when
used after other treatments. The drug had limited effectiveness in
patients with a lower level of MET amplification.

The results indicate that capmatinib may be an especially effective
treatment for patients who have NSCLC with MET exon 14 skipping mutations
and who have not been treated previously.

"There are many advances in NSCLC treatment that are helping people
live longer and better with their disease, and it is really important
that all newly diagnosed patients with NSCLC get broad molecular
profiling to determine what their optimal first-line therapy should
be," said senior author Rebecca Suk Heist, MD, investigator in the MGH
Cancer Center and assocoiate professor of Medicne at Harvard Medical
School. "If we don't test, we don't know." Heist noted that MET exon 14 skipping and amplification join a number of other drivers of NSCLC for
which researchers have developed targeted therapies. "It is critically important that all patients have their lung cancers tested for these to
know whether there is a targeted treatment option or not," she said.


========================================================================== Story Source: Materials provided by Massachusetts_General_Hospital. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Ju"rgen Wolf, Takashi Seto, Ji-Youn Han, Noemi Reguart, Edward
B. Garon,
Harry J.M. Groen, Daniel S.W. Tan, Toyoaki Hida, Maja de Jonge,
Sergey V.

Orlov, Egbert F. Smit, Pierre-Jean Souquet, Johan Vansteenkiste,
Maximilian Hochmair, Enriqueta Felip, Makoto Nishio, Michael
Thomas, Kadoaki Ohashi, Ryo Toyozawa, Tobias R. Overbeck, Filippo de
Marinis, Tae-Min Kim, Eckart Laack, Anna Robeva, Sylvie Le Mouhaer,
Maeve Waldron- Lynch, Banu Sankaran, O. Alejandro Balbin, Xiaoming
Cui, Monica Giovannini, Mikhail Akimov, Rebecca S. Heist. Capmatinib
in MET Exon 14- Mutated or MET-Amplified Non-Small-Cell Lung
Cancer. New England Journal of Medicine, 2020; 383 (10): 944 DOI:
10.1056/NEJMoa2002787 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200908131028.htm

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