Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer (#370)

Sara M Tolaney 1 , Kevin Kalinsky 2 , Virginia Kaklamani 3 , Claudio Savulsky 4 , Martin Olivo 5 , Gursel Aktan 6 , Peter A Kaufman 7 , Dongyuan Xing 5 , Ana Almonte 5 , Soamnauth Misir 5 , Vassiliki Karantza 6 , Louise Young 8 , Sami Diab 9
  1. Dana Farber Cancer Institute, Boston, USA
  2. Columbia University Medical Center, New York, NY, USA
  3. University of Texas Health Science Center, San Antonio, TX, USA
  4. Eisai Ltd, Hatfield, UK
  5. Eisai Inc., Woodcliff Lake, New Jersey, United States of America
  6. Merck Co. Inc, Kenilworth, New Jersey, USA
  7. Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
  8. Eisai Australia Pty Ltd, Melbourne, VIC, Australia
  9. Rocky Mountain Cancer Center, Denver, CO, USA

Aims: Eribulin mesylate is approved for patients with metastatic breast cancer and ≥2 prior chemotherapeutic regimens for metastatic disease. Pembrolizumab is approved for several advanced cancers.

Methods: This open-label phase 1b/2 study enrolled patients with metastatic triple-negative breast cancer and ≤2 prior lines of chemotherapy for metastatic disease. Recommended phase 2 dose: eribulin 1.4 mg/m2 on d1 and d8 and pembrolizumab 200 mg on d1 of a 21-d cycle. Primary endpoints: safety, tolerability (phase 1b), ORR (phase 2); secondary endpoints: PFS, OS, efficacy in PD-L1+ patients.

Results: We report data from 82/104 enrolled patients (data cut-off November 1, 2016). Most common treatment-emergent adverse events (TEAEs): fatigue (73.2%), nausea (51.2%), peripheral sensory neuropathy (46.3%), alopecia (43.9%), pyrexia (36.6%). Most common eribulin-related grade (G) 3/4 TEAEs: neutropenia (29.3%), peripheral neuropathy (8.5%), asthenia/fatigue (7.3%). 19.5% of patients had pembrolizumab-related G3/4 immune-related TEAEs. TEAEs leading to drug withdrawal/dose reduction: 18.3%/28.0% of patients. G5 events: 3 patients (respiratory failure, pleural effusion, multiple organ failure; none related to study drug). Response was irrespective of PD-L1 status.

 

 

Overall (n=82)

No prior chemotherapy in metastatic setting (n=48)

1-2 Prior lines of chemotherapy in metastatic setting (n=34)

PD-L1+

(n=35)

PD-L1–

(n=36)

ORR, n (%)

[95% CI]

21 (25.6)

[16.8, 35.4]

12 (25.0)

[14.0, 37.8]

9 (26.5)

[13.3, 41.8]

9 (25.7)

[12.9, 40.8]

9 (25.0)

[12.5, 39.8]

Clinical benefit rate, n (%)

25 (30.5)

13 (27.1)

12 (35.3)

10 (28.6)

12 (33.3)

Disease control rate, n (%)

46 (56.1)

28 (58.3)

18 (52.9)

19 (54.3)

21 (58.3)

Median PFS, months [95% CI]

4.1 [2.3-4.8]

4.1 [2.2-4.9]

3.9 [2.1-6.3]

4.1 [2.1-4.8]

4.1 [2.3-6.3]

Median OS, months [95% CI]

NE [17.7-NE]

17.7 [13.7-NE]

NE [13.1-NE]

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Conclusions: Eribulin+pembrolizumab resulted in improved ORR, longer PFS, OS, and comparable TEAEs to historical reports of either monotherapy. Further exploration of this combination is warranted.