Evidence map›Paper›PMID 34365220›Full record

ArticleTranslational oncology2021

Will the clinical development of 4th-generation "double mutant active" ALK TKIs (TPX-0131 and NVL-655) change the future treatment paradigm of ALK+ NSCLC?

Sai-Hong Ignatius Ou, Misako Nagasaka, Danielle Brazel, Yujie Hou, Viola W Zhu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed.

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  17. Overcoming Central β-Sheet #6 (Cβ6)Lung Cancer (Auckland, N.Z.) · 2024
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Sai-Hong Ignatius OuUniversity of California Irvine School of Medicine, 200 South Manchester Avenue, Suite 400, Orange, CA, United States; Chao Family Comprehensive Cancer Center, Orange, California, United States. Electronic address: siou@hs.uci.edu.
Misako NagasakaUniversity of California Irvine School of Medicine, 200 South Manchester Avenue, Suite 400, Orange, CA, United States; Chao Family Comprehensive Cancer Center, Orange, California, United States; St. Marianna University, School of Medicine, Kawasaki, Japan.
Danielle BrazelUniversity of California Irvine School of Medicine, 200 South Manchester Avenue, Suite 400, Orange, CA, United States.
Yujie HouSamuel Curtis Johnson Graduate School of Management, Cornell University, Ithaca, New York, United States.
Viola W ZhuUniversity of California Irvine School of Medicine, 200 South Manchester Avenue, Suite 400, Orange, CA, United States; Chao Family Comprehensive Cancer Center, Orange, California, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Our current treatment paradigm of advanced anaplastic lymphoma kinase fusion (ALK+) non-small cell lung cancer (NSCLC) classifies the six currently approved ALK tyrosine kinase inhibitors (TKIs) into three generations. The 2nd-generation (2G) and 3rd-generation (3G) ALK TKIs are all "single mutant active" with varying potencies across a wide spectrum of acquired single ALK resistance mutations. There is a vigorous debate among clinicians which is the best upfront ALK TKI is for the first-line (1L) treatment of ALK+ NSCLC and the subsequent sequencing strategies whether it should be based on the presence of specific on-target ALK resistance mutations or not. Regardless, sequential use of "single mutant active" ALK TKIs will eventually lead to double ALK resistance mutations in cis. This has led to the creation of fourth generation (4G) "double mutant active" ALK TKIs such as TPX-0131 and NVL-655. We discuss the critical properties 4G ALK TKIs must possess to be clinically successful. We proposed conceptual first-line, second-line, and molecularly-based third-line registrational randomized clinical trials designed for these 4G ALK TKIs. How these 4G ALK TKIs would be used in the future will depend on which line of treatment the clinical trial design(s) is adopted provided the trial is positive. If approved, 4G ALK TKIs may usher in a new treatment paradigm for advanced ALK+ NSCLC that is based on classifying ALK TKIs based on the intrinsic functional capabilities ("singe mutant active" versus "double mutant active") rather than the loosely-defined "generational" (first-, second-,third-,fourth-) classification and avoid the current clinical approaches of seemingly random sequential use of 2G and 3G ALK TKIs.

Indexed as

4th-generation ALK TKIALK+ NSCLCAnaplastic lymphoma kinase tyrosine kinase inhibitors“Double mutant active”NVL-655“Single mutant active”TPX-0131

Identifiers

PMID34365220
PMCPMC8353359

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.