Dana-Farber Cancer Institute, Boston, MA
Sara M. Tolaney , Kevin Kalinsky , Virginia G. Kaklamani , David R. D'Adamo , Gursel Aktan , Michaela L. Tsai , Ruth O'Regan , Peter A. Kaufman , Sharon Wilks , Eleni Andreopoulou , Debra A. Patt , Yuan Yuan , Grace Wang , Dongyuan Xing , Ella Kleynerman , Vassiliki Karantza , Sami Diab
Background: As monotherapies, both ERI (a chemotherapeutic microtubule inhibitor) and PEMBRO (a programmed death [PD]-1 blocking immunotherapy) have shown promising antitumor activity in mTNBC. Emerging data suggest that the addition of immunotherapy to traditional chemotherapy holds promise for mTNBC. This open-label, single-arm, phase 1b/2 study evaluated the safety and efficacy of ERI + PEMBRO in mTNBC. Methods: Patients (pts) with mTNBC and ≤2 prior systemic anticancer therapies for metastatic disease were enrolled and stratified by prior number of therapy (Stratum 1, 0; Stratum 2, 1–2). Pts received IV ERI 1.4 mg/m2 on day (d)1 and d8 and IV PEMBRO 200 mg on d1 of a 21-d cycle. The primary objectives were safety and objective response rate (ORR per RECIST 1.1 by independent imaging review). Assessments also included efficacy outcomes by PD ligand-1 (PD-L1) expression status; PD-L1+ was defined as a combined positive score ≥1 using the PD-L1 IHC 22C3 pharmDx. Results: As of data cutoff (July 31, 2019), 167 pts (Stratum 1, n=66; Stratum 2, n=101) were enrolled and treated. No dose-limiting toxicities were observed. The most common treatment-emergent adverse events were fatigue (66%), nausea (57%), peripheral sensory neuropathy (41%), alopecia (40%), and constipation (37%). No deaths were considered treatment related. The overall ORR was 23.4% (95% CI: 17.2–30.5). Efficacy outcomes by PD-L1 status (PD-L1+, n=74; PD-L1-, n=75) and stratum are presented (table). Conclusions: ERI + PEMBRO has activity in pts with mTNBC. There was a trend toward more robust activity for the combination among patients with PD-L1+ tumors compared to PD-L1- tumors in the first-line setting (Stratum 1); whereas, in the later-line setting (Stratum 2) similar survival outcomes were observed among the PD-L1+ and PD-L1- pts. ERI + PEMBRO shows promise for mTNBC with efficacy that appears greater than historical reports of either agent alone. Clinical trial information: NCT02513472.
ERI + PEMBRO | PD-L1+ Stratum 1 | PD-L1- Stratum 1 | PD-L1+ Stratum 2 | PD-L1- Stratum 2 |
---|---|---|---|---|
(N=149)a | (n=29) | (n=31) | (n=45) | (n=44) |
ORR, % | 34.5 | 16.1 | 24.4 | 18.2 |
(95% CI) | (17.9–54.3) | (5.5–33.7) | (12.9–39.5) | (8.2–32.7) |
mOS, months | 21.0 | 15.2 | 14.0 | 15.5 |
(95% CI) | (8.3–29.0) | (12.8–19.4) | (11.0–19.4) | (12.4–18.7) |
mPFS, months | 6.1 | 3.5 | 4.1 | 3.9 |
(95% CI) | (4.1–10.2) | (2.0–4.2) | (2.1–4.8) | (2.3–6.3) |
mDOR, months | 8.3 | 15.2 | 8.2 | 8.6 |
(95% CI) | (3.2–NE) | (6.5–22.2) | (5.1–25.1) | (3.5–13.2) |
aExcludes 18 patients who had unknown tumor PD-L1 status. DOR, duration of response; m, median; NE, not evaluable; OS, overall survival; PFS, progression-free survival.
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