LBA13 - Tumour infiltrating lymphocytes (TILs), PD-L1 expression and their dynamics in the NeoTRIPaPDL1 trial

Background

NeoTRIP, randomized 280 pts to 8 cycles of nab-paclitaxel/carbo (CT) or with atezolizumab (CT/A). 260 pts were evaluable for pCR as Per-Protocol Population.

Methods

We collected samples at baseline (n=260/260; 100%), on day 1 cycle 2 (d1c2) (n=228/260; 87.7%], and at surgery (SX) [n=231/260; 88.8%]. We assessed stromal and intratumoral TILs (sTILs, iTILs), and PD-L1 expression (SP142) on immune (IC) and tumor (TC) cells, their dynamics and association with pCR. We also aim to validate sTILs≥40% at d1c2 as predictive of pCR (Bianchini G ASCO 2020).

Results

Baseline PD-L1 IC was balanced (IC0 43.4%; IC1 37.6%; IC2/3 18.5%), but sTILs and iTILs were higher in CT arm (p=0.046, p=0.005). All baseline biomarkers were significantly associated with pCR in CT/A, but only PD-L1 was in CT arm. Considering log PD-L1 IC (to correct skewness) as continuous variable, OR were 3.42 [1.93-6.07] (p=0.00003) and 1.51 [1.04-2.21], (p=0.032) in CT/A and CT, respectively (interaction p=0.02). pCR for CT/A vs CT (and ΔpCR) by PD-L1 IC groups were 87.0% vs 72.0% [Δ15%] (IC2/3), 56.2% vs 44.0% [Δ12.2%] (IC1) and 35.1% vs 41.1% [Δ-6.0%] (IC0). After 1 cycle of treatment (d1c2), tumor cells were not found in 28.8% (CT/A) and 13.6% (CT) (p=0.003), which was predictive of pCR (78.2% vs 42.5%, p<0.0001). TILs increased at d1c2 in both arms (p<0.0001). PD-L1 IC+ did however increase from 45.4% to 74.7% in CT/A (p=0.03) (65.8% change to pos), but decreased from 52.7% to 37.9% in CT (p=0.0001) (44.0% change to neg). In CT/A, also PD-L1 TC+ increased for 2.7% to 36.5%. In both arms, sTILs at d1c2 were more informative than baseline sTILs and ΔTILs, e.g. in CT/A, sTILs≥40% had 71.4% pCR (OR 6.38 [2.24-20.9], p=0.0007). Conversion rate of PD-L1 IC baseline to surgery (SX) was 42.9% (- to + 28.6% and + to – 14.3%) and 30.3% (- to + 9.1% and + to – 21.2%) in CT/A and CT arms, respectively.

Conclusions

Baseline imbalance in sTILs and iTILs might have resulted in smaller differences of pCR between arms. Atezo increased pCR by more than 10% in “immune-rich” groups (PDL1 IC+, high sTILs/iTILs). PD-L1 dynamic is strong and divergent by arm, with atezo turning most PD-L1 neg to pos. D1c2 assessment provides an early surrogate of pCR, and high rate of tumor absence may suggests that shorter therapy may be enough for some cases.

Clinical trial identification

Neoadjuvant Therapy in TRIPle Negative Breast Cancer With antiPDL1 (NeoTRIPaPDL1) (NCT02620280).

Editorial acknowledgement

Legal entity responsible for the study

Fondazione Michelangelo.

Funding

Associazione Italiana per la Ricerca sul Cancro (AIR) (IG 2018 ID 21787), Breast Cancer Research Foundation, Roche, Celgene.

Disclosure

G. Bianchini: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Lilly; Advisory/Consultancy: Amgen; Advisory/Consultancy: Genomic Helath; Honoraria (self): Neopharm Israel; Advisory/Consultancy: Eisai; Advisory/Consultancy: Daiichi Sankyo; Honoraria (self): Chugai; Advisory/Consultancy: Sanofi. C-S. Huang: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): MSD; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: F. Hoffman-La Roche; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Obi; Research grant/Funding (institution): Eirgenix. D. Egle: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Lilly; Honoraria (self), Travel/Accommodation/Expenses: MSD. C. Zamagni: Honoraria (self): Takeda; Honoraria (self): Pierre Fabre; Honoraria (self): Teva; Honoraria (self): Istituto Gentili; Advisory/Consultancy: Roche; Advisory/Consultancy: Eisai; Advisory/Consultancy: Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Amgen; Advisory/Consultancy: Tesaro; Advisory/Consultancy: QuintilesIMS. M. Thill: Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Amgen; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Celgene; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Speaker Bureau/Expert testimony: MSD. E.M. Ciruelos: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. R. Greil: Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: AstaZeneca; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Sandoz; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Gilead; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: MSD. M.A. Colleoni: Honoraria (self): Novartis; Advisory/Consultancy: PierreFabre; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Puma Biotechnology; Advisory/Consultancy: OBI Pharma; Advisory/Consultancy: Celldex; Advisory/Consultancy: AstraZeneca. L. Del Mastro: Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Ipsen; Honoraria (self): Eli Lilly; Honoraria (self): Novartis; Honoraria (self): Takeda; Honoraria (self): MSD; Honoraria (self): Genomic Health; Travel/Accommodation/Expenses: Celgene. G. Viale: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche Genentech; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Travel/Accommodation/Expenses: Celgene. L. Gianni: Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: ADC Therapeutics; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Celgene; Advisory/Consultancy: GI Therapeutics; Advisory/Consultancy: Synthon; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Merk Sharp & Dome; Advisory/Consultancy: Genentech; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Odonate Therapeutics; Advisory/Consultancy: Sandoz; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: Tahio Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): Zymeworks; Advisory/Consultancy: Genenta; Advisory/Consultancy: MetIS; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Revolution Medicine; Advisory/Consultancy: CD47; Advisory/Consultancy: Synaffix; Research grant/Funding (institution): Daiichi Sankyo. All other authors have declared no conflicts of interest.