Roche Holding Ltd · SIX:RO
Roche — ESMO 2019
14 slides from Roche's conference presentation, 2019
Slide 1: Peripheral Neuropathy, Thrombocytopaenia, and CNS Recurrence: KATHERINE Trial Update
PERIPHERAL NEUROPATHY, THROMBOCYTOPAENIA, AND CENTRAL NERVOUS SYSTEM RECURRENCE: AN UPDATE OF THE PHASE III KATHERINE TRIAL OF POST- NEOADJUVANT TRASTUZUMAB EMTANSINE (T-DM1) OR TRASTUZUMAB IN PATIENTS WITH RESIDUAL INVASIVE HER2-POSITIVE BREAST CANCER Michael Untch1, Charles E. Geyer, Jr.2, Chiun-S
Slide 2: Disclosures
DISCLOSURES Consulting fees from the following companies have been paid to Prof. Untch’s institution: Abbvie, Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly Germany, Lilly International, Merck, MSD Mundipharma, Myriad Genetics, Novartis, Odonate, Pierre Fabre, Pfizer, PUMA Biotechnology,
Slide 3: Background
BACKGROUND • Patients with HER2-positive early breast cancer who have residual invasive disease following neoadjuvant treatment have worse outcomes than those with a complete response1–5 • The KATHERINE study (NCT01772472) investigated the use of adjuvant T-DM1 versus trastuzumab in patients with HE
Slide 4: KATHERINE Study Design
KATHERINE STUDY DESIGN • cT1-4/N0-3/M0 at presentation (cT1a-b/N0 excluded) T-DM1 • Centrally confirmed HER2-positive BC 3.6 mg/kg IV Q3W • Neoadjuvant therapy R 14 cycles 1:1 – ≥6 cycles of chemotherapy – ≥9 weeks of taxane and trastuzumab • Residual invasive tumour in breast or N=1486 Trastuzumab
Slide 5: Primary Endpoint: Invasive Disease-Free Survival
PRIMARY ENDPOINT: INVASIVE DISEASE-FREE SURVIVAL 100 Invasive Disease-Free Survival Rate, % 80 60 Trastuzumab T-DM1 Trastuzumab T-DM1 (n=743) (n=743) 40 IDFS Events, no. (%) 165 (22.2) 91 (12.2) Unstratified HR=0.50 (95% CI, 0.39–0.64) 20 P<0.0001 3-year IDFS 77.0% 88.3% 0 Median follow-up time: ~40
Slide 6: Effect of Baseline Peripheral Neuropathy on Treatment-Induced Peripheral Neuropathy
EFFECT OF BASELINE PERIPHERAL NEUROPATHY ON TREATMENT-INDUCED PERIPHERAL NEUROPATHY On-Study BL No BL Peripheral Neuropathy Neuropathy Neuropathya • BL neuropathy was well balanced between (safety population) T-DM1 H T-DM1 H treatment arms: T-DM1 22.7%; H 21.4% All Grades, % 36.3 17.5 31.1 16.8 • In
Slide 7: Effect of Prior Taxane Type on Incidence of Peripheral Neuropathy
EFFECT OF PRIOR TAXANE TYPE ON INCIDENCE OF PERIPHERAL NEUROPATHY On-Study • The type of neoadjuvant taxane was similar Docetaxel Paclitaxel Peripheral between treatment arms: Neuropathy – Docetaxel: T-DM1 54%; H 57% T-DM1 H T-DM1 H (safety (n=402) (n=411) (n=351) (n=319) – Paclitaxel: T-DM1 47%; H
Slide 8: Effect of Prior Platinum Therapy on T-DM1–Associated Thrombocytopaenia
EFFECT OF PRIOR PLATINUM THERAPY ON T-DM1–ASSOCIATED THROMBOCYTOPAENIA Prior platinum No prior platinum • Overall, 20% of patients received prior Thrombocytopaenia (safety population) carboplatin or cisplatin T-DM1 H T-DM1 H (T-DM1 arm 19%, H arm 21%) All Grades, % 36.2 3.3 26.7 2.1 Grade 1 15.6 3.3
Slide 9: CNS Recurrence: Background
CNS RECURRENCE: BACKGROUND Site of First Invasive Disease Event • In the primary KATHERINE Event, n (%) T-DM1 (n=743) H (n=743) results, there was a Any Invasive-Disease Event 91 (12.2) 165 (22.2) numerically higher rate of CNS recurrence as first site of Category of Invasive Event recurrence in the
Slide 10: Higher CNS Recurrence as First IDFS Event Likely Due to Competing Risk
HIGHER CNS RECURRENCE AS FIRST IDFS EVENT IS LIKELY DUE TO COMPETING RISK; T-DM1 WAS NOT ASSOCIATED WITH AN INCREASED OVERALL RISK OF CNS RECURRENCE T-DM1 H • The numerically higher rate of CNS recurrence as a first CNS Recurrence IDFS event in the T-DM1 arm may be explained by (n=743) (n=743) Patie
Slide 11: Overall Survival Is Similar Between Treatment Arms After CNS Recurrence
OVERALL SURVIVAL IS SIMILAR BETWEEN TREATMENT ARMS AFTER CNS RECURRENCE • There was no evidence that the numerically higher rate of CNS recurrence as a first event in the T-DM1 arm had a detrimental impact on overall survival • Between the two treatment arms, there was: – Similar time from CNS recur
Slide 12: Overall Survival After CNS Recurrence at Any Time
OVERALL SURVIVAL AFTER CNS RECURRENCE AT ANY TIME 1.0 Proportion Event-Free 0.8 Unstratified HR (95% CI)=1.07 (0.60–1.91) 0.6 0.4 0.2 Trastuzumab (n=40) T-DM1 (n=45) 0.0 0 6 12 18 24 30 36 42 48 54 60 No. of patients at risk Time (mo) Trastuzumab 40 24 14 9 7 4 3 0 0 0 0 T-DM1 45 30 19 11 5 3 2 1 1
Slide 13: Summary and Conclusions
SUMMARY AND CONCLUSIONS • In KATHERINE, regardless of treatment arm, baseline neuropathy was associated with a longer duration and a lower resolution rate of treatment-associated peripheral neuropathy • The type of neoadjuvant taxane received did not influence the incidence of peripheral neuropathy
Slide 14: Acknowledgements
ACKNOWLEDGEMENTS • The patients and their families • The KATHERINE investigators and clinical study sites • This trial was sponsored by F. Hoffmann-La Roche Ltd • Medical writing assistance for this presentation was provided by Twist Medical and funded by F. Hoffmann-La Roche, Ltd Access slides at: