Evidence map›Paper›PMID 40957338›Full record

ArticleLung cancer (Amsterdam, Netherlands)2025

Clinical factors and molecular co-alterations impact outcomes in patients receiving first-line osimertinib for EGFR-mutated non-small cell lung cancer.

Fangdi Sun, Mandeep K Banwait, Surbhi Singhal, Amanda Herrmann, Zofia Piotrowska, Karen Yun, Lyudmila Bazhenova, Ayman T Ullah, Emily W Guo, Heather A Wakelee and 6 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Lung cancer (Amsterdam, Netherlands), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–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

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
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

16 authors.

Fangdi SunDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Mandeep K BanwaitMassachusetts General Hospital Cancer Center, Boston, MA, USA.
Surbhi SinghalDivision of Hematology/Oncology, Department of Medicine, University of California Davis, Sacramento, CA, USA.
Amanda HerrmannUniversity of California San Diego Moores Cancer Center, La Jolla, CA, USA.
Zofia PiotrowskaMassachusetts General Hospital Cancer Center, Boston, MA, USA.
Karen YunUniversity of California San Diego Moores Cancer Center, La Jolla, CA, USA.
Lyudmila BazhenovaUniversity of California San Diego Moores Cancer Center, La Jolla, CA, USA.
Ayman T UllahDivision of Hematology/Oncology, Department of Medicine, University of California Davis, Sacramento, CA, USA.
Emily W GuoDivision of Hematology/Oncology, Department of Medicine, University of California Davis, Sacramento, CA, USA.
Heather A WakeleeDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Joel W NealDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Millie S DasDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA; Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA, USA.
Kavitha J RamchandranDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Mohana RoyDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA.
Maximilian DiehnStanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
Nathaniel J MyallDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA. Electronic address: nmyall@stanford.edu.

Funding

UC Davis Paul Calabresi K12 Clinical Oncology Research Career Development ProgramK12CA138464 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI BIRKELAND, ANDREW CHARLES, LARA, PRIMO N. · 2011 to 2025
$11.4M
The Activation of ERBB3 Signaling as a Resistance Mechanism to Targeted TherapiesR01CA137008 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Aaron N Hata, ZOFIA PIOTROWSKA · 2009 to 2026
$5.7M
NCI NIH HHS K12 CA138464NCI NIH HHS R01 CA137008
6 · The paper itself

Abstract

purposeUntil recently, osimertinib was the preferred first-line therapy for nearly all patients with EGFR-mutated advanced NSCLC. However, with approval of the FLAURA2 and MARIPOSA regimens, identifying molecular or clinical factors that confer higher risk for inferior outcomes to first-line osimertinib may better inform upfront treatment selection for newly-diagnosed patients.

methodsThis real-world, multicenter retrospective study across 4 U.S. academic centers included adult patients with metastatic NSCLC and classic sensitizing EGFR mutations (exon 19 deletion, L858R mutation) receiving first-line osimertinib monotherapy who had tissue-based next-generation sequencing performed at diagnosis. Survival analyses for time-to-treatment discontinuation (TTD) on osimertinib and overall survival (OS) were conducted by number of co-alterations, individual gene alterations, previously defined molecular pathways, and clinical factors.

resultsA total of 219 patients were included (median age 68, 62 % female, 51 % with baseline CNS metastases). TP53 was most frequently co-altered (58 %), followed by EGFR amplification (13 %), CDKN2A (10 %), RB1 (9 %), and PIK3CA (8 %). Number of de novo co-alterations and presence of co-alterations by molecular pathway did not significantly predict TTD or OS. Co-alteration of both TP53 and PIK3CA, but not TP53 alone, demonstrated significantly shorter median OS compared to the TP53 and PIK3CA wild-type population (21.9 vs 39.5 months, p = 0.046), with similar numerical trend for median TTD. On multivariate analysis, L858R mutation and CNS and bone metastases remained significant predictors for inferior clinical outcomes.

conclusionCo-alteration of TP53 and PIK3CA may represent a high-risk molecular subgroup of EGFR-mutated NSCLC, however both clinical and molecular features should be considered in risk stratification.

Indexed as

AcrylamidesAniline CompoundsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungLung NeoplasmsMutationAdultAgedAged, 80 and overErbB ReceptorsFemaleHumansIndolesMaleMiddle AgedPrognosisAcrylamidesAniline CompoundsAntineoplastic AgentsEGFR protein, humanErbB ReceptorsIndolesosimertinibProtein Kinase InhibitorsPyrimidinesTumor Suppressor Protein p53Co-alterationCo-mutationEGFRNSCLCOsimertinibPIK3CATP53

Identifiers

PMID40957338
PMCPMC12937006

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.