Abstract 1211P
Background
In IMpower010 (NCT02486718), ctDNA+ status after surgery (post-op) was associated with poor prognosis; atezo was beneficial vs BSC regardless of post-op ctDNA status (Zhou ESMO-IO 2021). Post-chemo, ctDNA clearance (ctDNA−; 62% of post-op ctDNA+ pts) was associated with improved DFS; ctDNA levels were maintained in ctDNA+ pts, and conversion to ctDNA+ was delayed with atezo in ctDNA− pts (Felip ESMO-IO 2022). At final DFS and 2nd IA of overall survival (OS) with ≥5y of follow up, DFS benefit with atezo continued to translate into a positive OS trend vs BSC in PD-L1 tumour cell (TC) ≥1% and TC ≥50% stage II-IIIA pts. We report updated DFS and OS by ctDNA and PD-L1 status.
Methods
Pts with resected (R0) stage IB-IIIA NSCLC and ECOG PS 0-1 who had 1-4 cycles of chemo post-op were randomised 1:1 to atezo 1200 mg Q3W (16 cycles) or BSC. We analysed DFS and OS by ctDNA and PD-L1 (by SP263 IHC) status in post-op ctDNA evaluable pts with stage II-IIIA NSCLC. Plasma samples for ctDNA testing were collected post-op before chemo and post-chemo at Cycle 1 (post-op ctDNA+ pts only) and analysed per the Natera Signatera RUO assay.
Results
Of 1005 randomised pts, 600 were ctDNA evaluable. At data cutoff (26 Jan 2024), 112 of 534 post-op pts (21%) were ctDNA+. DFS and OS outcomes by ctDNA and PD-L1 status are in the table. Median DFS was longer in pts with ctDNA‒ vs ctDNA+ post-op and post-chemo. Longer DFS was seen with atezo vs BSC regardless of ctDNA status. In the post-op PD-L1 TC ≥1% population, a trend toward OS benefit was seen in ctDNA+ and ctDNA‒ pts.
Conclusions
Post-op and post-chemo ctDNA positivity was a negative prognostic factor for DFS after 5y of follow up. Regardless of ctDNA status, DFS and OS benefit with atezo vs BSC was seen in pts with stage II-IIIA PD-L1 TC ≥1% NSCLC. Chemo-mediated ctDNA– was associated with longer DFS. DFS was longer with atezo vs BSC regardless of post-chemo ctDNA status. Table: 1211P
DFS and OS by ctDNA and PD-L1 status in stage II-IIIA ctDNA-evaluable pts
| Group | ctDNA status | PD-L1 status | Median DFS, mo | HR (95%CI) | ||
| Atezo | BSC | |||||
| Post-op | ‒ | All | n=218NE | n=20460.6 | 0.74 (0.56, 0.98) | |
| TC ≥1% | n=124NE | n=9852.6 | 0.60 (0.40, 0.89) | |||
TC Clinical trial identificationNCT02486718. Editorial acknowledgementMedical writing assistance for this manuscript was provided by Bena Lim, PhD, CMPP, of Nucleus Global, an Inizio Company, and funded by F. Hoffmann-La Roche Ltd. Legal entity responsible for the studyF. Hoffmann-La Roche Ltd. FundingF. Hoffmann-La Roche, Ltd. DisclosureH. Wakelee: Financial Interests, Personal, Advisory Board, Served on a DSMC, completed November 2022: Mirati; Financial Interests, Personal, Invited Speaker, Develop and present a series of lectures: Fishawack Facilitate LTD; Financial Interests, Personal, Invited Speaker, Series of CME lectures: Medscape, Research to Practice; Financial Interests, Personal, Other, Discussion of new data at conferences: Curio Science; Financial Interests, Personal, Invited Speaker, Series of lectures/webinars for PER/OncLive: MJH Holdings; Financial Interests, Personal, Invited Speaker, CME lecture: Axis Medical Education, ParadigmMC, Prova Education; Financial Interests, Personal, Advisory Board: IOBiotech; Financial Interests, Personal, Invited Speaker, Facilitated speaking at several virtual conferences: Shanghai Bird Translation and Consulting; Financial Interests, Personal, Invited Speaker, Invited speaker at virtual symposium: China International Medical Foundation; Financial Interests, Personal, Invited Speaker, Invited to speak and moderate at JLCS meetings: Japanese Lung Cancer Society; Financial Interests, Personal, Invited Speaker, Presented at several CME conferences: Medical Educator Consortium; Financial Interests, Personal, Invited Speaker, Facilitated discussion of recent data: IDEOlogy Health; Financial Interests, Personal, Invited Speaker, Invited CME lecture: Vindico Medical Education; Financial Interests, Personal, Invited Speaker, Invited speaker at symposium: Taiwan Association for the Study of Lung Cancer (TASLC); Financial Interests, Personal, Royalties, I receive royalties for a chapter I wrote for UpToDate: UpToDate; Financial Interests, Institutional, Local PI, Clinical Trial Conduct: AstraZeneca/MedImmune, BMS, Seagen, Xcovery; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Conduct: Genentech/Roche, Merck; Financial Interests, Institutional, Local PI, clinical trial conduct: Helsinn; Financial Interests, Institutional, Coordinating PI, IIT for single site: Bayer; Financial Interests, Personal, Steering Committee Member, uncompensated steering committee member: Merck, AstraZeneca, Genentech/Roche; Financial Interests, Personal, Other, uncompensated advisory board participation: BMS; Non-Financial Interests, Officer, Past President: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Leadership Role, Executive Committee: ECOG-ACRIN. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Merck, Novartis, Regeneron, Roche, Sanofi, GSK, Pfizer; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Biontech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, MSD, Mirati, Pfizer, Regeneron, Roche, Sanofi, GSK, Lilly; Financial Interests, Personal, Other, Member of DMSB: Daiichi Sankyo; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Amgen, Boehringer Ingelheim, Beigene, Daiichi Sankyo, GSK, BMS, Lilly, MSD, Regeneron, Roche; Financial Interests, Institutional, Local PI: Pfizer Seagen. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, Beigene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. N.K. Altorki: Financial Interests, Institutional, Research Grant, clinical trial: AstraZeneca. E. Vallieres: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Merck, Oncocyte. S. Oizumi: Financial Interests, Personal, Other, Honorarium: AstraZeneca, Chugai Pharmaceutical, MSD. H. Tanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai pharmaceutical, Boehringer Ingelheim, Eli Lilly, MSD, Ono pharmaceutical, Merck, Novartis, Takeda pharmaceutical, Pfizer, Daiichi Sankyo pharmaceutical, Taiho pharmaceutical, Bristol Myers Squibb, EISAI, Hisamitsu pharmaceutical, Nippon Kayaku; Financial Interests, Institutional, Local PI: Chugai pharmaceutical, Merck, AstraZeneca, MSD, Eli Lilly, Ono pharmaceutical, Bristol Myers Squibb, Merck, Takeda pharmaceutical, Taiho pharmaceutical, Pfizer, Daiichi Sankyo pharmaceutical, AbbVie, Amgen, Janssen pharmaceutical. S. McCune: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Genentech; Financial Interests, Institutional, Local PI, Funding for Clinical Trial: Genentech. E. Bennett: Financial Interests, Personal, Full or part-time Employment: Genentech, Roche; Financial Interests, Personal, Stocks or ownership: Genentech, Roche. B.J. Gitlitz: Financial Interests, Personal, Full or part-time Employment: Genentech, Roche; Financial Interests, Personal, Stocks or ownership: Genentech, Roche. V.A. McNally: Financial Interests, Personal, Full or part-time Employment: Genentech, Roche; Financial Interests, Personal, Stocks or ownership: Genentech, Roche. S. Novello: Financial Interests, Personal, Invited Speaker: AZ, MSD, Eli Lilly, Novartis, Beigene, Amgen, Thermo Fisher; Financial Interests, Personal, Advisory Board: BI, BMS, Pfizer, Takeda, Roche, Sanofi, Amgen, J&J; Financial Interests, Institutional, Coordinating PI, IIT: MSD, BI; Financial Interests, Institutional, Coordinating PI: AZ, AMG, Eli Lilly, Sanofi, J&J, Roche; Non-Financial Interests, Leadership Role, president of this European advocacy: WALCE; Non-Financial Interests, Member: IASLC, AIOM, ASCO. M. Ballinger: Financial Interests, Personal, Full or part-time Employment: Genentech, Roche; Financial Interests, Personal, Stocks or ownership: Genentech, Roche. W. Zou: Financial Interests, Personal, Full or part-time Employment: Genentech, Roche; Financial Interests, Personal, Stocks or ownership: Genentech, Roche. B. Nabet: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. M. Srivastava: Financial Interests, Personal, Full or part-time Employment: Genentech, Roche; Financial Interests, Personal, Stocks or ownership: Genentech, Roche. C. Zhou: Financial Interests, Personal, Advisory role, Consulting fees: Innovent Biologics, Qilu, Hengrui, TopAlliance Biosciences Inc.; Financial Interests, Personal, Other, Payment or honoraria from: Eli Lilly China, Sanofi, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Qilu, Hengrui, Innovent Biologics, Alice, C-Stone, LUYE Pharma, TopAlliance Biosciences Inc., Amoy Diagnostics, AnHeart. All other authors have declared no conflicts of interest. Resources from the same session1111P - Genomic and transcriptomic analysis of Japanese melanoma reveals candidate biomarkers for immune checkpoint inhibitor respondersPresenter: Toshihiro Kimura Session: Poster session 04 1112P - Immunotherapy after progression to double immunotherapy: Pembrolizumab and Lenvatinib versus conventional chemotherapy for patients with metastatic melanoma after failure of PD-1/CTLA-4 inhibitionPresenter: Dimitrios Ziogas Session: Poster session 04 1113P - A machine learning model based on computed tomography radiomics to predict prognosis in subjects with stage IV melanomaPresenter: Maria Teresa Maccallini Session: Poster session 04 1114P - Deciphering unresectable in-transit metastasis in melanoma: Multi-modal and longitudinal insightsPresenter: Giuseppe Tarantino Session: Poster session 04 1115P - Multiomics clustering of patients with cutaneous melanoma to reveal survival trends based on tumor immune evasion featuresPresenter: Adeliya Leleytner Session: Poster session 04 1116P - Application of the Scottish inflammatory prognostic score to the south-east Scotland cancer network real-world melanoma cohortPresenter: Karim El-Shakankery Session: Poster session 04 1117P - Intratumoral microbiota is associated with prognosis in Chinese patients with skin melanomaPresenter: Hang Jiang Session: Poster session 04 1118P - Immunological alterations during neoadjuvant BRAF/MEK inhibition in patients with prior unresectable regionally advanced melanoma: Translational analysis from the REDUCTOR trialPresenter: Femke Burgers Session: Poster session 04 1119P - Genomic and transcriptomic predictors of resistance to anti-PD1 monotherapy in patients with advanced melanomaPresenter: Wenya Wang Session: Poster session 04 1120P - Tumoral and peripheral immunophenotype of patients with stage II/III melanoma undergoing adjuvant immunotherapy following tumor resectionPresenter: Maria Ascierto Session: Poster session 04 This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
| ||||||