Background

Early dynamic patterns (DP) of ctDNA and TKa provide improved prediction of progression free survival for pts with HR+ HER2− ABC treated with RIB+LET enrolled in the BioItaLEE trial. Here we evaluate their association with tumor response.

Methods

Of the 287 pts enrolled, 236 with post-baseline imaging evaluation were included in the present analyses. Clinical benefit rate (CBR) was defined according to Recist Critera 1.1. According to presence or absence of MUT ctDNA at cycle (C)1 day (D)1 and C1D15, ctDNA DP were defined as: Confirmed Wild Type (WT) (WT/WT), New mutated (MUT) (WT/MUT), Cleared (MUT/WT), confirmed MUT (MUT/MUT). TKa DP were defined as TKa inhibited (INH; +/-/-), rebounded (+/-/+) and insufficiently INH (+/+/+) according to the presence (+) or absence (-) of TKa at C1D1, C1D15 and C2D1. Multivariate logistic regression models adjusting for pts status, tumor type, visceral metastases and number of organs involved were used to correlate CBR with ctDNA and TKa dynamics.

Results

Overall CBR was 73.3%. CBR according to ctDNA and TKa DP is shown in the table. In the logistic model, MUT/MUT vs WT/WT pts had an Odds Ratio (OR) of 0.42 (p=0.033). OR of TKa rebounded vs. TKa INH pts and TKa insufficiently INH vs. TKa INH pts were 0.38 (p=0.019) and 0.24 (p=0.008) respectively (Table).

Table: 199P

Conclusions

DP of either ctDNA and TKa were associated with tumor response to RIB+LET. Our data suggest that insufficient inhibition of TKa at C1D15 may be a surrogate marker for tumor progression. If further confirmed, TKa measurement may be helpful for patients needing a rapid evaluation of tumor response.

Clinical trial identification

NCT03439046.

Legal entity responsible for the study

Novartis Farma S.p.A.

Funding

Novartis Farma SpA, Italy.

Disclosure

G. Arpino: Financial Interests, Personal, Writing Engagements, Medical writing: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi Sankyo, Novartis, Roche, Pfizer, Eli Lilly, Gilead, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Novartis, Roche, Seagen, Viatris; Financial Interests, Personal, Other, Support for attending meetings: Daiichi Sankyo, Roche, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Novartis, Gilead, Roche, Seagen. G. Bianchini: Financial Interests, Personal, Advisory Role: Novartis, Eli Lilly, Pfizer, Roche, AstraZeneca, Neopharm Istrael, Amgen, MSD, Chugai, Sanofi, Daiichi Sankyo, Eisai, Gilead, Seagen, Exact Science, Agendia, Seagen. L. Malorni: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Seagen. R. Caputo: Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly, Veracyte, Seagen; Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, Roche, Gilead, MSD, AstraZeneca, Daiichi Sankyo. A. Zambelli: Financial Interests, Personal, Advisory Board: Roche, Novartis, Eli Lilly, Pfizer, Daiichi Sankyo, AstraZeneca, Seagen, Exact Science, MSD. F. Puglisi: Financial Interests, Institutional, Research Grant: AstraZeneca, Eisai, Roche; Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly; Financial Interests, Personal, Invited Speaker: Pfizer. L. Del Mastro: Financial Interests, Institutional, Research Grant: Eli Lilly, Novartis, Roche, Daiichi Sankyo, Seagen; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Eli Lilly, AstraZeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Science, Ipsen; Financial Interests, Personal, Other, Support for attending meetings or travel: Roche, Pfizer, Eisai, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Novartis, Roche, Eli Lilly, Pfizer, Daiichi Sankyo, Exact Science, Gilead, Pierre Fabre, Eisai, AstraZeneca, Agendia, GSK, Seagen. M.A. Colleoni: Financial Interests, Institutional, Research Grant: Roche. F. Montemurro: Financial Interests, Personal, Advisory Role: Roche, Novartis, Daiichi Sankyo, AstraZeneca, MSD, Eli Lilly, Pierre Fabre. G.V. Bianchi: Financial Interests, Personal, Advisory Board: Novartis, Daiichi Sankyo, AstraZeneca, Seagen, Eli Lilly; Financial Interests, Personal, Invited Speaker: Roche, BMS. I. Paris: Financial Interests, Personal, Advisory Board: Novartis, Seagen, Gilead, Italfarmaco, Pfizer, Seagen, Gilead; Financial Interests, Personal and Institutional, Invited Speaker: Eli Lilly; Financial Interests, Personal, Training: AstraZeneca, Sophos. M.E. Cazzaniga: Non-Financial Interests, Personal, Advisory Board: Novartis. M. Orditura: Non-Financial Interests, Institutional, Advisory Role: AORN Caserta Oncologia Medica. C. Zamagni: Financial Interests, Personal, Research Grant: Novartis, Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, MSD, Eisai, GSK; Financial Interests, Personal, Other, Support for attending meeting or travel: Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, MSD, Eisai, GSK, Exact Science, Clovis; Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, MSD, Eisai, GSK, Daiichi Sankyo. M.B. Suter: Financial Interests, Personal, Full or part-time Employment: Novartis. N. Fenderico: Financial Interests, Personal, Full or part-time Employment: Novartis. M. De Laurentiis: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Novartis, Roche, Pfizer, Seagen, Daiichi Sankyo, MSD, GSK, Sanofi, Celltrion, Organon, Eisai, Pierre Fabre, Menarini, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, Novartis, Roche, Pfizer, Seagen, Daiichi Sankyo, MSD, GSK, Sanofi, Eisai, Pierre Fabre, Menarini, Gilead. All other authors have declared no conflicts of interest.