Category: Lung Cancer

  • QuickView: Sunvozertinib vs Chemotherapy in Advanced EGFR exon20ins NSCLC (WU-KONG28)

    WU-KONG28 ASCO 2026

    Sunvozertinib vs platinum-based chemotherapy · First-line advanced NSCLC with EGFR exon20ins · International randomized phase 3

    Total N
    324
    1:1 randomized
    Median PFS
    10.3 vs 7.5 mo
    Sunvo vs Chemo
    Hazard Ratio
    0.65
    95% CI 0.50–0.85 · P<0.001
    Confirmed ORR
    58.9% vs 31.1%
    Sunvo vs Chemo

    WU-KONG28 Study Design

    Key Eligibility
    • Locally advanced or metastatic non-squamous NSCLC
    • Documented EGFR exon20ins
    • Newly diagnosed or treatment-naïve
    • ECOG PS 0 or 1
    Randomization
    Ratio1:1
    StratificationBaseline brain metastasis (yes / no)
    Sites154 sites · 15 countries
    Data cutoffJanuary 16, 2026
    Sunvozertinib (N=163)
    300 mg once daily, oral
    Continuous until progression or unacceptable toxicity
    Platinum-based Chemotherapy (N=161)
    Carboplatin AUC5 + pemetrexed 500 mg/m² Q3W
    Up to 4 or 6 cycles (investigator discretion) → pemetrexed maintenance
    Crossover to sunvozertinib allowed at confirmed PD
    Endpoints
    Primary PFS assessed by BICR Key Secondary Overall Survival (OS) Secondary Investigator-assessed PFS · ORR · DCR · DoR · Tumor size change · Safety · PK Exploratory PFS2

    Efficacy

    Primary Endpoint: Median PFS (BICR)
    Sunvozertinib10.3 mo
    95% CI: 8.3, 14.0
    Chemotherapy7.5 mo
    95% CI: 6.7, 8.5
    HR (95% CI)0.65 (0.50, 0.85)
    P value<0.001
    PFS Landmark Rates
    12 months46.1% vs 26.7%
    18 months33.2% vs 17.1%
    24 months23.0% vs 10.3%
    Median follow-up: 24.0 mo (sunvo) · 18.0 mo (chemo)
    Objective Response Rate (BICR)
    Confirmed ORR
    Sunvozertinib58.9%
    95% CI: 50.9, 66.5
    Chemotherapy31.1%
    95% CI: 24.0, 38.8
    Odds Ratio (95% CI)3.2 (2.0, 5.0)
    Additional Response Data (from ASCO presentation)
    Best ORR68.1% vs 35.4%
    Disease Control Rate94.5% vs 85.7%
    Duration of Response
    Sunvozertinib11.2 mo
    95% CI: 8.2, 13.9
    Chemotherapy7.1 mo
    95% CI: 6.9, 11.1
    Median follow-up: 22.1 mo (sunvo) · 13.8 mo (chemo)
    Median Tumor Size Shrinkage
    Sunvozertinib-42.1%
    Range: -88.6 to 21.3
    Chemotherapy-24.7%
    Range: -85.6 to 362.2
    Crossover
    101 of 112 chemotherapy-arm patients (90.2%) with confirmed disease progression crossed over to receive sunvozertinib.
    Interim Overall Survival
    Sunvozertinib29.8 mo
    95% CI: 21.8, NE
    Chemotherapy28.8 mo
    95% CI: 20.7, NE
    HR (95% CI)0.99 (0.70, 1.40)
    P value0.48
    Data maturity38.9% (126/324 events)
    OS Landmark Rates
    18 months65.5% vs 67.2%
    24 months57.4% vs 56.2%
    30 months50.0% vs 49.1%
    Median OS follow-up: 26.1 mo (sunvo) · 26.7 mo (chemo). OS data immature; interpretation may be confounded by the crossover design. NE, not estimable.
    Subgroup Analysis: BICR-assessed PFS
    ← Favors sunvozertinib HR = 1.0 Favors chemotherapy →
    Overall(n=324)
    0.65 (0.50, 0.85)
    Age Group
    <65 years(n=182)
    0.62 (0.44, 0.87)
    ≥65 years(n=142)
    0.71 (0.46, 1.07)
    Sex
    Female(n=192)
    0.68 (0.48, 0.97)
    Male(n=132)
    0.58 (0.39, 0.85)
    Race
    Asian(n=204)
    0.56 (0.41, 0.77)
    Non-Asian(n=120)
    0.93 (0.58, 1.48)
    Region
    North America + EU(n=102)
    0.78 (0.47, 1.30)
    Others(n=222)
    0.62 (0.45, 0.84)
    Smoking History
    Never(n=208)
    0.61 (0.43, 0.85)
    Ever(n=116)
    0.73 (0.48, 1.11)
    Baseline ECOG
    0(n=89)
    0.77 (0.45, 1.31)
    ≥1(n=235)
    0.62 (0.46, 0.84)
    Brain Metastasis at Baseline
    With(n=41)
    0.96 (0.44, 2.08)
    Without(n=283)
    0.62 (0.47, 0.83)
    EGFR Exon20ins Subtype
    769_ASV(n=103)
    0.46 (0.29, 0.73)
    770_SVD(n=53)
    NR
    Other/Unknown(n=168)
    0.77 (0.53, 1.10)
    EGFR Exon20ins Region
    Near loop(n=220)
    0.59 (0.43, 0.82)
    Far loop(n=84)
    0.83 (0.49, 1.38)
    C-helix/Unknown(n=20)
    NR
    Disease-Related Surgery
    With(n=65)
    0.55 (0.29, 1.02)
    Without(n=259)
    0.69 (0.51, 0.92)
    X-axis range: 0.2 to 2.5. NR = not reported (insufficient events). Source: Heymach et al, ASCO 2026 LBA8500 (slide 7).

    Safety

    Sunvozertinib N=163; Chemotherapy N=150 (patients who received randomized treatment)
    Safety Overview
    ParameterSunvozertinib %Chemotherapy %
    Any adverse event100.099.3
    Any AE, Grade ≥375.556.7
    Any TRAE100.097.3
    Any TRAE, Grade ≥361.349.3
    Treatment-related SAE18.412.7
    TRAE leading to dose interruption45.427.3
    TRAE leading to dose reduction40.524.0
    TRAE leading to discontinuation7.411.3
    TRAE with fatal outcome0.00.7
    Top TRAEs leading to dose interruption and reduction with sunvozertinib: CPK increased and diarrhea (neither led to treatment discontinuation).
    Adverse Events ≥20% in Either Group (Any Grade)
    All-cause adverse events emerging during treatment (per NEJM Table 3). Grade ≥3 shown in adjacent column.
    Sunvo
    G≥3
    Chemo
    G≥3
    Diarrhea
    87.1%
    14.1%
    16.7%
    —
    CPK increased
    58.3%
    20.9%
    4.0%
    0.7%
    Anemia
    57.1%
    9.2%
    62.7%
    11.3%
    Rash
    52.8%
    0.6%
    6.7%
    —
    Paronychia
    48.5%
    3.7%
    0.7%
    —
    Weight decreased
    43.6%
    3.7%
    11.3%
    0.7%
    Decreased appetite
    38.7%
    1.8%
    28.0%
    1.3%
    Creatinine increased
    33.7%
    0.6%
    9.3%
    —
    Nausea
    28.2%
    1.8%
    46.0%
    1.3%
    Vomiting
    28.2%
    1.8%
    24.0%
    2.0%
    Hypokalemia
    25.2%
    3.7%
    7.3%
    0.7%
    Amylase increased
    23.3%
    1.2%
    11.3%
    —
    Lipase increased
    23.3%
    5.5%
    7.3%
    1.3%
    AST increased
    22.1%
    2.5%
    37.3%
    0.7%
    Mouth ulceration
    20.2%
    1.2%
    3.3%
    —
    ALT increased
    17.8%
    1.8%
    34.7%
    1.3%
    Fatigue
    15.3%
    1.2%
    20.0%
    2.7%
    Neutrophil ↓
    14.7%
    2.5%
    45.3%
    18.7%
    WBC ↓
    12.3%
    0.6%
    39.3%
    6.7%
    Constipation
    11.0%
    0.6%
    25.3%
    —
    Platelet ↓
    9.2%
    2.5%
    22.0%
    6.7%
    Sunvozertinib AEs reflect wild-type EGFR inhibition (diarrhea, rash, paronychia, CPK elevation). Chemotherapy-associated myelosuppression (anemia, neutropenia, thrombocytopenia) predominates in the chemo arm.

    References

    1. Heymach JV, Liu G, Xing L, et al. Sunvozertinib monotherapy versus platinum-based chemotherapy as first-line treatment for advanced NSCLC with EGFR exon20ins: primary analysis of a multinational phase 3 randomized study (WU-KONG28). J Clin Oncol. 2026;44(suppl 17):LBA8500. doi:10.1200/JCO.2026.44.17_suppl.LBA8500. Presented at: 2026 ASCO Annual Meeting; May 29–June 2, 2026; Chicago, IL.
    2. Zhou C, Greillier L, Liu G, et al. First-line sunvozertinib in NSCLC with EGFR exon 20 insertion mutations. N Engl J Med. 2026. doi:10.1056/NEJMoa2604461.
    3. ClinicalTrials.gov identifier: NCT05668988.

    Abbreviations

    BICRBlinded Independent Central Review
    cORRConfirmed Objective Response Rate
    CPKCreatine phosphokinase
    DCRDisease Control Rate
    DoRDuration of Response
    ECOGEastern Cooperative Oncology Group
    EGFREpidermal Growth Factor Receptor
    Exon20insExon 20 Insertion Mutations
    HRHazard Ratio
    mPFSMedian Progression-Free Survival
    NSCLCNon-Small Cell Lung Cancer
    ORRObjective Response Rate
    OSOverall Survival
    PFSProgression-Free Survival
    PFS2Second Progression-Free Survival
    Q3WEvery 3 Weeks
    SAESerious Adverse Event
    TKITyrosine Kinase Inhibitor
    TRAETreatment-Related Adverse Event
    CANCER COMMUNICATOR · cancercommunicator.com
    Data sources: ASCO LBA8500 presentation · NEJM 10.1056/NEJMoa2604461 · Data cutoff: January 16, 2026
  • #ASCO26: First-Line Sunvozertinib Prolongs PFS in EGFR Exon 20 Insertion–Mutated Advanced NSCLC

    #ASCO26: First-Line Sunvozertinib Prolongs PFS in EGFR Exon 20 Insertion–Mutated Advanced NSCLC

    The oral EGFR tyrosine kinase inhibitor sunvozertinib significantly improved progression-free survival (PFS) compared with carboplatin–pemetrexed as first-line treatment for advanced nonsquamous non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations in the phase 3, international WU-KONG28 trial. Results of the primary analysis were reported in an opening Oral Abstract Session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in the New England Journal of Medicine.

    WU-KONG28 enrolled adults with previously untreated, locally advanced stage IIIB or IIIC or metastatic stage IV nonsquamous NSCLC harboring EGFR exon 20 insertions, an Eastern Cooperative Oncology Group performance-status score of 0 or 1, and adequate organ function. Patients with brain metastases were eligible if the metastases were stable after local therapy. From December 2022 through May 2025, 324 patients from 154 sites in 15 countries were randomly assigned 1:1 to oral sunvozertinib 300 mg once daily (n = 163) or carboplatin–pemetrexed administered every 3 weeks for up to 4 or 6 cycles, at investigator discretion, followed by pemetrexed maintenance therapy (n = 161). Randomization was stratified by baseline brain metastasis status. Patients in the chemotherapy group could cross over to sunvozertinib after disease progression was confirmed by blinded independent central review (BICR).

    The primary end point was BICR-assessed PFS according to RECIST version 1.1. The key secondary end point was overall survival (OS); other secondary end points included investigator-assessed PFS, objective response, change in tumor size, and duration of response. The data cutoff for the primary analysis was January 16, 2026.

    At a median follow-up of 24.0 months in the sunvozertinib group and 18.0 months in the chemotherapy group, median BICR-assessed PFS was 10.3 months with sunvozertinib compared with 7.5 months with chemotherapy. Sunvozertinib reduced the risk of disease progression or death by 35% (HR, 0.65; 95% CI, 0.50–0.85; P < .001). PFS rates at 12 months were 46.1% and 26.7%, respectively; at 18 months, rates were 33.2% and 17.1%; and at 24 months, rates were 23.0% and 10.3%.

    Objective response by BICR was reported in 58.9% of patients treated with sunvozertinib compared with 31.1% of those treated with chemotherapy. Median best percentage change from baseline in tumor size was −42.1% with sunvozertinib and −24.7% with chemotherapy. Median duration of response was 11.2 months and 7.1 months, respectively.

    OS data were immature at 38.9% maturity. At a median OS follow-up of 26.1 months with sunvozertinib and 26.7 months with chemotherapy, 62 and 64 patients, respectively, had died. Median OS was 29.8 months with sunvozertinib and 28.8 months with chemotherapy (HR, 0.99; 95% CI, 0.70–1.40; P = .48). Interpretation of OS is limited by maturity and the crossover design: among 112 patients in the chemotherapy group with BICR-confirmed disease progression, 101 (90.2%) crossed over to sunvozertinib.

    Safety analyses included 163 patients treated with sunvozertinib and 150 treated with chemotherapy. Grade 3 or higher adverse events occurred in 75.5% and 56.7% of patients, respectively. The most common grade 3 or higher adverse events with sunvozertinib were increased serum creatine kinase level (20.9%), diarrhea (14.1%), and anemia (9.2%); with chemotherapy, the most common were decreased neutrophil count (18.7%), anemia (11.3%), decreased white-cell count (6.7%), and decreased platelet count (6.7%). Serious adverse events were reported in 45.4% of patients receiving sunvozertinib and 26.7% receiving chemotherapy.

    Adverse events led to drug discontinuation in 11.7% of patients treated with sunvozertinib and 12.0% treated with chemotherapy; treatment-related adverse events led to discontinuation in 7.4% and 11.3%, respectively. Interstitial lung disease and pneumonitis led to sunvozertinib discontinuation in 1.8% and 1.2% of patients. No treatment-related fatal adverse events occurred with sunvozertinib; 1 treatment-related fatal pneumonia event occurred in the chemotherapy group.

    Table. Key Efficacy Outcomes in WU-KONG28

    EndpointSunvozertinib (n = 163)Chemotherapy (n = 161)
    Median PFS by BICR, mo10.37.5
           HR (95% CI); P0.65 (0.50–0.85); < .001
    PFS at 12 mo, %46.126.7
    PFS at 18 mo, %33.217.1
    PFS at 24 mo, %23.010.3
    Objective response by BICR, %58.931.1
    Median DOR, mo11.27.1
    Median OS, mo29.828.8
    OS at 24 mo, %57.456.2


    Abbreviations: BICR, blinded independent central review; CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio; NSCLC, non–small-cell lung cancer; OS, overall survival; PFS, progression-free survival; DOR, duration of response.

    References

  • Four-Year Median OS with Osimertinib/ Chemotherapy Combination in Advanced EGFR-Mutation Positive NSCLC

    he final overall survival (OS) analysis from the FLAURA2 trial was presented during the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC) Presidential Symposium, firmly establishing osimertinib plus chemotherapy as a new first-line standard for patients with advanced epidermal growth factor receptor (EGFR)-mutated non–small cell lung cancer (NSCLC). The final OS analysis showed the longest survival yet reported in this population from a global phase 3 trial.

    FLAURA2 enrolled 557 patients with untreated, locally advanced or metastatic EGFR exon 19 deletion or L858R NSCLC. Patients with stable brain metastases were allowed on study. Participants were randomized to receive osimertinib with carboplatin or cisplatin plus pemetrexed for four cycles followed by maintenance osimertinib–pemetrexed, or osimertinib monotherapy at 80 mg daily. Treatment beyond progression was permitted if investigators judged clinical benefit. Subsequent therapy was at investigator discretion. Progression-free survival (PFS) was the primary endpoint, and OS was a key secondary endpoint.

    At the primary PFS analysis (data cut April 2023), the addition of chemotherapy reduced the risk of progression by 38% (HR 0.62; 95% CI 0.49–0.79; p<0.001), with median PFS of 25.5 months versus 16.7 months for osimertinib alone. These benefits were consistent across prespecified subgroups, including patients with brain metastases and those harboring L858R mutations.

    With extended follow-up to June 2025 (57% maturity), median OS reached 47.5 months in the osimertinib–chemotherapy arm compared with 37.6 months with osimertinib monotherapy (HR 0.77; 95% CI 0.61–0.96; p=0.02). Three-year OS was 63% versus 51%, respectively. The OS advantage was maintained across all predefined subgroups.

    Median osimertinib exposure was 30.5 months with the combination, versus 21.2 months with monotherapy. The median pemetrexed exposure in the experimental arm was 8.3 months, suggesting many patients experienced a prolonged chemotherapy-free interval.

    Patterns of subsequent therapy highlighted clinical practice implications. After progression, platinum-based chemotherapy was the most common second-line treatment in both arms, given to 44% of patients in the combination arm and 72% after osimertinib alone. Importantly, the OS benefit for the upfront combination was preserved despite widespread use of platinum rechallenge after monotherapy.

    Grade ≥3 adverse events (AEs) were more common with the combination (70% vs 34%). Anemia, diarrhea, nausea, and decreased appetite were the most common any-grade AEs.  Adverse events led to discontinuation of osimertinib in 12% of patients in the combination arm and 7% with monotherapy. No new safety signals or treatment-related deaths emerged during longer follow-up.

    These findings build on the FLAURA2 PFS advantage and confirm clinically meaningful OS improvement. Median OS of nearly four years represents the longest survival reported for EGFR-mutated NSCLC in a phase 3 global study. With compelling evidence across subgroups and no excess late toxicity, osimertinib plus chemotherapy is now firmly positioned as the frontline standard of care for EGFR-mutated advanced NSCLC.

    References

    Planchard D, Jänne PA, Kobayashi K, et al. First-line osimertinib plus chemotherapy versus osimertinib monotherapy in EGFR-mutated advanced NSCLC: FLAURA2 final overall survival. Presented at: IASLC World Conference on Lung Cancer (WCLC) 2025; September 7, 2025; Barcelona, Spain. Abstract PL01.06.

  • FDA Approves Sunvozertinib for EGFR Exon 20 Insertion-Positive Metastatic NSCLC

    On July 2, 2025, the U.S. Food and Drug Administration (FDA) granted accelerated approval to sunvozertinib for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations, (as detected by an FDA-approved test), whose disease has progressed on or after platinum-based chemotherapy.

    Sunvozertinib is an oral EGFR tyrosine kinase inhibitor. The approval was based on the phase WU-KONG6 multicenter study evaluating sunvozertinib monotherapy in patients with previously treated EGFR exon 20 insertion–positive NSCLC. The objective response rate was 46% with a median duration of response of 11.1 months.

    US Food and Drug website. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sunvozertinib-metastatic-non-small-cell-lung-cancer-egfr-exon-20. Accessed July 9, 2025.