Phase III tucatinib + T-DM1 vs placebo + T-DM1 in HER2+ metastatic breast cancer. Sustained PFS HR 0.74; final OS HR 0.98 — not significant.
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Trial slides shared by KOLs at ESMO Breast 2026 (#ESMOBreast26). Click any image to expand. OCR text extracted via AWS Textract.
[Slide 1] PFS WIN... BUT OS FLAT. Does tucatinib + T-DM1 still matter? HER2CLIMB-02 UPDATED RESULTS ARMS (1:1) TRIAL HER2CLIMB-02 SETTING T-DM1 + Tucatinib Prev. treated T-DM1 + Placebo BRAIN METS HER2+ MBC Included n = 463 PFS PFS IN OVERALL SURVIVAL (INVESTIGATOR ASSESSED) BRAIN METS (OS) 9.5 mo 7.8 mo 43.3 mo T-DM1 + Tucatinib T-DM1 + Tucatinib T-DM1 + Tucatinib vs vs vs 7.4 mo 5.7 mo 41.0 mo T-DM1 + Placebo T-DM1 + Placebo T-DM1 + Placebo HR 0.74 HR 0.74 HR 0.98 (95% CI 0.592-0.921) (95% CI 0.539-1.010) (95% CI 0.762-1.269) Even in brain mets: os 35.8 mo (TUC) vs 34.4 mo (Control)
[Slide 1] ESMO BREAST CANCER 423RO 2026 Annual Congress Addition of tucatinib to trastuzumab emtansine (T-DM1) in patients with previously treated HER2+ locally advanced/metastatic breast cancer (LA/MBC): updated efficacy analysis from the HER2CLIMB-02 trial Giuseppe Curigliano, 1,2 Virginia F. Borges,³ Joyce O'Shaughnessy,⁴ Alicia Okines,⁵,⁶ Sara M. Tolaney,⁷ Cristina Saura,8 Antonio C. Wolff,9 Sherene Loi, 10 Norikazu Masuda,11 Linda Vahdat, 12 Binghe Xu, 13 Danica Chiu,¹ 14 Diqiong Xie, 15 Nissa Abbasi, 16 Kelechi Olu,¹⁷ Sara A. Hurvitz¹⁸ European Institute of Oncology. IRCCS, Milano, Italy; Department of Oncology and Hematology-Oncology, University of Milano, Milano, Italy; University of Colorado Cancer Center, Aurora, CO, USA; "Baylor University Medical Center, Texas Oncology. US Oncology, Dallas, TX, USA; The Royal Marsden NHS Foundation Trust, London, UK: The Institute of Cancer Research, London, UK; Dana-Farber Cancer Institute, Boston, MA, USA; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; "Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD. USA; "Peter MacCallum Cancer Centre, Melbourne, Australia; "Graduate School of Medicine, Kyoto University, Kyoto, Japan; "Dartmouth Health, Lebanon, NH, USA; 13Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China; ¹⁴Pfizer Inc. London, UK; ¹⁵Pfizer Inc, Washington DC, USA; "Pfizer Inc. Seattle, WA, USA; "Pfizer AG, Zurich, Switzerland; *Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA 6-8 May 2026 ESMO --- [Slide 2] STUDY DESIGN HER2CLIMB-02 (NCT03975647) is a randomized, double-blind, placebo-controlled, phase 3 trial assessing the efficacy and safety of tucatinib versus placebo, combined with T-DM1 in patients with HER2+ LA/MBC. Treatments Endpoints Tucatinib (300 mg orally BID) Primary Key eligibility criteria + PFS per investigator assessment ≥ 18 years of age T-DM1 Secondary Centrally confirmed (3.6 mg/kg IV every 21 days) OS HER2+ LA/MBC (n = 228) Prior treatment with R PFS & OS in BM subgroup 1:1 trastuzumab and a taxane Placebo (orally BID) Tumor response Patients with BM were + PFS per BICR permitted T-DM1 Safety (3.6 mg/kg IV every 21 days) Stratification factors Other (n = 235) LOT for metastatic disease (1L or other) Subsequent systemic anticancer HR status (positive or negative) Presence/history of BM (yes or no) therapies ECOG PS (0 or 1) 1L, first-line: BICR, blinded independent central review; BID, twice a day; BM, brain metastases; ECOG PS, Eastern Cooperative Oncology Group performance status, HER2+, human epidermal growth factor receptor 2-positive; HR+, hormone receptor-positive; IV, intravenous: LA/MBC, locally advanced/metastatic breast cancer; LOT, line of treatment; OS, overall survival; PFS, progression-free survival; R, randomization; T-DM1, trastuzumab emtansine. ESMO Content of this resentation - of the Permission - required for --- [Slide 3] RESULTS: OVERALL SURVIVAL Median follow-up for OS: 50.7 months Total population Patients with baseline BM 1.0 Arm Event/N Median (95% CI) 1.0 Arm Event/N Median (95% CI) 0.9 TUC + T-DM1 121/228 43.3 mos (34.4-58.5) 0.9 TUC + T-DM1 56/99 35.8 mos (25.5-52.5) 0.8 PBO + T-DM1 122/235 41.0 mos (37.6-53.6) 0.8 PBO + T-DM1 63/105 34.4 mos (28.2-47.8) 0.7 0.7 OS probability 0.6 os probability 0.6 0.5 0.5 0.4 0.4 0.3 0.3 0.2 + Censored 0.2 + Censored 0.1 HR = 0.983 (95% CI, 0.762-1.269); Stratified logrank P value = 0.8959 0.1 HR = 0.886 (95% CI, 0.616-1.275); Stratified logrank P value = 0.5146 0.0 0.0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 Time from randomization (months) Time from randomization (months) Patients at risk Patients at risk TUC T-DM1 228 225 217 209 202 191 183 165 151 146 140 129 121 114 108 99 81 53 33 20 11 4 1 0 TUC T-DM1 99 98 94 91 87 82 77 66 60 57 54 51 47 45 44 40 30 21 13 7 5 2 1 0 PBO T-DM1 235 227 221 212 201 193 185 176 171 153 140 133 125 115 103 98 74 49 31 23 13 8 3 0 PBO . T-DM1 105 102 98 94 87 80 74 70 66 60 55 51 44 39 35 33 25 14 6 3 2 2 0 0 No significant difference in OS between treatment arms in the total study population and those with baseline BM BM, brain metastases; CI, confidence interval; HR, hazard ratio; mos, months; OS, overall survival: PBO, placebo; T-DM1, trastuzumab emtansine; TUC, tucatinib. ESMO Content of this presentation IS convright and responsibility of the author Permission is required for 100 USE --- [Slide 4] SUBSEQUENT SYSTEMIC ANTICANCER THERAPIES Arm First subsequent line of therapy Second subsequent line of therapy TUC + T-DM1 PBO + T-DM1 TUC + T-DM1 PBO + T-DM1 (n = 215)a (n = 229)a (n = 215)ᵃ (n = 229)a Subsequent systemic therapy received, n (%) 180 (83.7) 201 (87.8) 108 (50.2) 102 (44.5) Cytotoxic agent 50 (23.3) 62 (27.1) 55 (25.6) 50 (21.8) HER2-directed therapy Monoclonal antibody 57 (26.5) 60 (26.2) 41 (19.1) 41 (17.9) Antibody-drug conjugate 100 (46.5) 115 (50.2) 41 (19.1) 36 (15.7) T-DXdb 73 (34.0) 88 (38.4) 37 (17.2) 36 (15.7) Small molecule inhibitor 32 (14.9) 33 (14.4) 24 (11.2) 29 (12.7) Tucatinibᵇ 23 (10.7) 22 (9.6) 16 (7.4) 16 (7.0) Lapatinibᵇ 7 (3.3) 10 (4.4) 7 (3.3) 11 (4.8) Neratinibb 2 (0.9) 0 1 (0.5) 2 (0.9) "Patients who discontinued study treatment. Agent was either a monotherapy or included in a regimen. Similar proportions of patients in both arms received subsequent anticancer therapies. T-DXd was the preferred first subsequent anti-HER2 therapy in both arms. ~10% of patients received first subsequent regimens containing tucatinib. HER2, human epidermal growth factor receptor 2; PBO. placebo; T-DM1, trastuzumab emtansine; T-DXd. trastuzumab deruxtecan; TUC, tucatinib ESMO
[Slide 1] CONCLUSIONS In HER2CLIMB-02, the final OS analysis after 50.7 months of follow-up did not show a statistically significant difference between treatment arms. The updated PFS analysis with longer follow-up confirmed the benefit of tucatinib + T-DM1 over the control arm in previously treated patients with HER2+ LA/MBC, consistent with the primary analysis, with a similar benefit seen in patients with BM. Similar proportions of patients received subsequent anticancer therapies in both arms, with T-DXd as the preferred first subsequent anti-HER2 therapy. In this updated analysis, the safety profile of tucatinib + T-DM1 was consistent with the primary analysis with no new safety signals identified. BM, brain metastases; HER2+, human epidermal growth factor receptor 2-positive; LA/MBC, locally advanced/metastatic breast cancer; OS, overall survival; PFS, progression-free survival; T-DM1. trastuzumab emtansine; T-DXd, trastuzumab deruxtecan. Content of this presentation is copyright and responsibility of the author Permission is required for use ESMO
[Slide 1] ESMO BREAST CANCER 423RO 2026 Annual Congress Addition of tucatinib to trastuzumab emtansine (T-DM1) in patients with previously treated HER2+ locally advanced/metastatic breast cancer (LA/MBC): updated efficacy analysis from the HER2CLIMB-02 trial Giuseppe Curigliano, 1,2 Virginia F. Borges,³ Joyce O'Shaughnessy,⁴ Alicia Okines,⁵.⁶ Sara M. Tolaney,⁷ Cristina Saura,⁸ Antonio C. Wolff,9 Sherene Loi, 10 Norikazu Masuda,¹¹ Linda Vahdat, 12 Binghe Xu, 13 Danica Chiu,¹ 14 Diqiong Xie, 15 Nissa Abbasi, 16 Kelechi Olu,¹⁷ Sara A. Hurvitz18 European Institute of Oncology, IRCCS, Milano, Italy; Department of Oncology and Hematology-Oncology, University of Milano, Milano, Italy; University of Colorado Cancer Center, Aurora, CO, USA; "Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA; The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK; Dana-Farber Cancer Institute, Boston, MA, USA; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD, USA; "Peter MacCallum Cancer Centre, Melbourne, Australia; Graduate School of Medicine, Kyoto University, Kyoto, Japan; 12Dartmouth Health, Lebanon, NH, USA; 13Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China; 14Pfizer Inc. London, UK; 15Pfizer Inc, Washington DC, USA; ¹⁶Pfizer Inc, Seattle, WA, USA; "Pfizer AG, Zurich, Switzerland; 18Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA 6-8 May 2026 ESMO --- [Slide 2] STUDY DESIGN HER2CLIMB-02 (NCT03975647) is a randomized, double-blind, placebo-controlled, phase 3 trial assessing the efficacy and safety of tucatinib versus placebo, combined with T-DM1 in patients with HER2+ LA/MBC. Treatments Endpoints Tucatinib (300 mg orally BID) Primary Key eligibility criteria + PFS per investigator assessment ≥ 18 years of age T-DM1 Secondary Centrally confirmed (3.6 mg/kg IV every 21 days) OS HER2+ LA/MBC (n = 228) Prior treatment with R PFS & OS in BM subgroup 1:1 trastuzumab and a taxane Placebo (orally BID) Tumor response Patients with BM were + PFS per BICR permitted T-DM1 Safety (3.6 mg/kg IV every 21 days) Stratification factors Other (n = 235) LOT for metastatic disease (1L or other) Subsequent systemic anticancer HR status (positive or negative) Presence/history of BM (yes or no) therapies ECOG PS (0 or 1) 1L, first-line: BICR, blinded independent central review; BID, twice a day; BM, brain metastases; ECOG PS, Eastern Cooperative Oncology Group performance status, HER2+, human epidermal growth factor receptor 2-positive; HR+, hormone receptor-positive; IV, intravenous; LA/MBC, locally advanced/metastatic breast cancer; LOT, line of treatment; OS, overall survival; PFS, progression-free survival; R, randomization; T-DM1, trastuzumab emtansine. ESMO Content of this presentation is copyright and responsibility of the author Permission is required for re- use --- [Slide 3] RESULTS: OVERALL SURVIVAL Median follow-up for OS: 50.7 months Total population Patients with baseline BM 1.0 Arm Event/N Median (95% CI) 1.0 Arm Event/N Median (95% CI) 0.9 TUC + T-DM1 121/228 43.3 mos (34.4-58.5) 0.9 TUC + T-DM1 56/99 35.8 mos (25.5-52.5) 0.8 PBO + T-DM1 122/235 41.0 mos (37.6-53.6) 0.8 PBO + T-DM1 63/105 34.4 mos (28.2-47.8) 0.7 0.7 OS probability 0.6 os probability 0.6 0.5 0.5 0.4 0.4 0.3 0.3 0.2 + Censored 0.2 + Censored 0.1 HR = 0.983 (95% CI, 0.762-1.269); Stratified logrank P value = 0.8959 0.1 HR = 0.886 (95% CI, 0.616-1.275); Stratified logrank P value = 0.5146 0.0 0.0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 Time from randomization (months) Time from randomization (months) Patients at risk Patients at risk TUC T-DM1 228 225 217 209 202 191 183 165 151 146 140 129 121 114 108 99 81 53 33 20 11 4 1 0 TUC T-DM1 99 98 94 91 87 82 77 66 60 57 54 51 47 45 44 40 30 21 13 / 5 2 1 0 PBO T-DM1 235 227 221 212 201 193 185 176 171 153 140 133 125 115 103 98 74 49 31 23 13 8 3 0 PBO + T-DM1 105 102 98 94 87 80 74 70 66 60 55 51 44 39 35 33 25 14 6 3 2 2 0 0 No significant difference in OS between treatment arms in the total study population and those with baseline BM BM, brain metastases; CI, confidence interval; HR, hazard ratio; mos, months; OS, overall survival; PBO, placebo; T-DM1, trastuzumab emtansine; TUC, tucatinib. ESMO Content of this presentation is copyright and responsibility of the author Permission is required for use --- [Slide 4] SUBSEQUENT SYSTEMIC ANTICANCER THERAPIES Arm First subsequent line of therapy Second subsequent line of therapy TUC + T-DM1 PBO + T-DM1 TUC + T-DM1 PBO + T-DM1 (n = 215)a (n = 229)a (n = 215)a (n = 229)a Subsequent systemic therapy received, n (%) 180 (83.7) 201 (87.8) 108 (50.2) 102 (44.5) Cytotoxic agent 50 (23.3) 62 (27.1) 55 (25.6) 50 (21.8) HER2-directed therapy Monoclonal antibody 57 (26.5) 60 (26.2) 41 (19.1) 41 (17.9) Antibody-drug conjugate 100 (46.5) 115 (50.2) 41 (19.1) 36 (15.7) T-DXdb 73 (34.0) 88 (38.4) 37 (17.2) 36 (15.7) Small molecule inhibitor 32 (14.9) 33 (14.4) 24 (11.2) 29 (12.7) Tucatinibᵇ 23 (10.7) 22 (9.6) 16 (7.4) 16 (7.0) Lapatinibᵇ 7 (3.3) 10 (4.4) 7 (3.3) 11 (4.8) Neratinibᵇ 2 (0.9) 0 1 (0.5) 2 (0.9) "Patients who discontinued study treatment Agent was either a monotherapy or included in a regimen. Similar proportions of patients in both arms received subsequent anticancer therapies. T-DXd was the preferred first subsequent anti-HER2 therapy in both arms. ~10% of patients received first subsequent regimens containing tucatinib. HER2, human epidermal growth factor receptor 2; PBO, placebo; T-DM1, trastuzumab emtansine; T-DXd. trastuzumab deruxtecan; TUC, tucatinib. ESMO Content of this presentation is copyricht and responsibility of the author Permission is required for re use
[Slide 1] IN GERMANY AY 2026 ESMO ESMO BREAST CANCER 423RO 2026 Annual Congress Addition of tucatinib to trastuzumab emtansine (T-DM1) in patients with previously treated HER2+ locally advanced/metastatic breast cancer (LA/MBC): updated efficacy analysis from the HER2CLIMB-02 trial Giuseppe Curigliano, 1,2 Virginia F. Borges,³ Joyce O'Shaughnessy,⁴ Alicia Okines, 5,6 Sara M. Tolaney,⁷ Cristina Saura,⁸ Antonio C. Wolff,9 Sherene Loi, 10 Norikazu Masuda,11 Linda Vahdat, 12 Binghe Xu, 13 Danica Chiu,¹⁴ Diqiong Xie, 15 Nissa Abbasi, 16 Kelechi Olu,¹⁷ Sara A. Hurvitz18 European Institute of Oncology, IRCCS, Milano, Italy; 2Department of Oncology and Hematology-Oncology, University of Milano, Milano, Italy; University of Colorado Cancer Center, Aurora, CO, USA; "Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA; The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK; Dana-Farber Cancer Institute, Boston, MA, USA; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD, USA; 10Peter MacCallum Cancer Centre, Melbourne, Australia; "Graduate School of Medicine, Kyoto University, Kyoto, Japan; 12Dartmouth Health, Lebanon, NH, USA; 13Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China; ¹⁴Pfizer Inc. London, UK; 15Pfizer Inc, Washington DC, USA; 16Pfizer Inc. Seattle, WA, USA; ¹/Pfizer AG, Zurich, Switzerland; ¹⁸Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA 6-8 May 2026 ESMO ESMO BREAST CANCER --- [Slide 2] BERLIN GERMANY 6-8 MAY 2026 ESMO RESULTS: OVERALL SURVIVAL Median follow-up for OS: 50.7 months Total population Patients with baseline BM 1.0 Arm Event/N Median (95% CI) 1.0 Arm Event/N Median (95% CI) 0.9 TUC + T-DM1 121/228 43.3 mos (34.4-58.5) 0.9 TUC + T-DM1 56/99 35.8 mos (25.5-52.5) 0.8 PBO + T-DM1 122/235 41.0 mos (37.6-53.6) 0.8 PBO + T-DM1 63/105 34.4 mos (28.2-47.8) 0.7 0.7 os probability 0.6 os probability 0.6 0.5 0.5 0.4 0.4 0.3 0.3 0.2 + Censored 0.2 + Censored 0.1 HR = 0.983 (95% CI, 0.762-1.269); Stratified logrank P value = 0.8959 0.1 HR = 0.886 (95% CI, 0.616-1.275); Stratified logrank P value = 0.5146 0.0 0.0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 Time from randomization (months) Time from randomization (months) Patients at risk Patients at risk TUC T-DM1 228 225 217 209 202 191 183 165 151 146 140 129 121 114 108 99 81 53 33 20 11 4 1 0 TUC T-DM1 99 98 94 91 87 82 77 66 60 57 54 51 47 45 44 40 30 21 13 7 5 2 1 0 PBO T-DM1 235 227 221 212 201 193 185 176 171 153 140 133 125 115 103 98 74 49 31 23 13 8 3 0 PBO + T-DM1 105 102 98 94 87 80 74 70 66 60 55 51 44 39 35 33 25 14 6 3 2 2 0 0 No significant difference in OS between treatment arms in the total study population and those with baseline BM BM, brain metastases; CI, confidence interval; HR, hazard ratio; mos, months; OS, overall survival; PBO, placebo; T-DM1, trastuzumab emtansine; TUC, tucatinib. ESMO Content of this presentation is copyright and responsibility of the author Permission is required for re use ESMO BREAST CANCER --- [Slide 3] ERLIN GERMANY MAY 2026 ESMO CONCLUSIONS In HER2CLIMB-02, the final OS analysis after 50.7 months of follow-up did not show a statistically significant difference between treatment arms. The updated PFS analysis with longer follow-up confirmed the benefit of tucatinib + T-DM1 over the control arm in previously treated patients with HER2+ LA/MBC, consistent with the primary analysis, with a similar benefit seen in patients with BM. Similar proportions of patients received subsequent anticancer therapies in both arms, with T-DXd as the preferred first subsequent anti-HER2 therapy. In this updated analysis, the safety profile of tucatinib + T-DM1 was consistent with the primary analysis with no new safety signals identified. BM, brain metastases; HER2+, human epidermal growth factor receptor 2-positive; LA/MBC, locally advanced/metastatic breast cancer; OS, overall survival; PFS, progression-free survival; T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan. Content of this presentation is copyright and responsibility of the author Permission is required for use ESMO ESMO BREAST CANCER
[Slide 1 — Title + Authors] ESMO BREAST CANCER 2026 Annual Congress — Abstract 423RO Addition of tucatinib to trastuzumab emtansine (T-DM1) in patients with previously treated HER2+ locally advanced/metastatic breast cancer (LA/MBC): updated efficacy analysis from the HER2CLIMB-02 trial Giuseppe Curigliano, Virginia F. Borges, Joyce O'Shaughnessy, Alicia Okines, Sara M. Tolaney, Cristina Saura, Antonio C. Wolff, Sherene Loi, Norikazu Masuda, Linda Vahdat, Binghe Xu, Danica Chiu, Diqiong Xie, Nissa Abbasi, Kelechi Olu, Sara A. Hurvitz. European Institute of Oncology IRCCS Milan; University of Milan; CO/Aurora Cancer Center; Baylor/Texas Oncology/US Oncology; Royal Marsden NHS Trust; Institute of Cancer Research London; Dana-Farber Cancer Institute; Vall d'Hebron VHIO Barcelona; Sidney Kimmel Comprehensive Cancer Center Johns Hopkins; Peter MacCallum Cancer Centre Melbourne; Kyoto University; Dartmouth Health; Cancer Hospital Chinese Academy of Medical Sciences Beijing; Pfizer Inc; Fred Hutchinson Cancer Center / University of Washington. Presented 6-8 May 2026. [Slide 2 — Study Design] HER2CLIMB-02 (NCT03975647) is a randomized, double-blind, placebo-controlled, phase 3 trial assessing the efficacy and safety of tucatinib versus placebo, combined with T-DM1 in patients with HER2+ LA/MBC. Treatments: Tucatinib (300 mg orally BID) + T-DM1 (3.6 mg/kg IV every 21 days), n=228 vs Placebo orally BID + T-DM1 IV every 21 days, n=235. Key eligibility: ≥18 years of age, centrally confirmed HER2+ LA/MBC, prior treatment with trastuzumab and a taxane, patients with BM permitted. Stratification factors: LOT for metastatic disease (1L or other), HR status (positive or negative), presence/history of BM (yes or no), ECOG PS (0 or 1). Primary endpoint: PFS per investigator assessment. Secondary endpoints: OS, PFS & OS in BM subgroup, tumor response, PFS per BICR, safety, subsequent systemic anticancer therapies. [Slide 3 — RESULTS: OVERALL SURVIVAL] Median follow-up for OS: 50.7 months. Total population: TUC + T-DM1: events 121/228, median OS 43.3 mos (95% CI 34.4-58.5) PBO + T-DM1: events 122/235, median OS 41.0 mos (95% CI 37.6-53.6) HR = 0.983 (95% CI 0.762-1.269); Stratified log-rank P value = 0.8959 Patients with baseline BM: TUC + T-DM1: events 56/99, median OS 35.8 mos (95% CI 25.5-52.5) PBO + T-DM1: events 63/105, median OS 34.4 mos (95% CI 28.2-47.8) HR = 0.886 (95% CI 0.616-1.275); Stratified log-rank P value = 0.5146 "No significant difference in OS between treatment arms in the total study population and those with baseline BM." [Slide 4 — SUBSEQUENT SYSTEMIC ANTICANCER THERAPIES] First subsequent line of therapy (TUC+T-DM1 n=215 vs PBO+T-DM1 n=229): Subsequent systemic therapy received: 180 (83.7%) vs 201 (87.8%) Cytotoxic agent: 50 (23.3%) vs 62 (27.1%) HER2-directed monoclonal antibody: 57 (26.5%) vs 60 (26.2%) HER2-directed antibody-drug conjugate: 100 (46.5%) vs 115 (50.2%) T-DXd: 73 (34.0%) vs 88 (38.4%) HER2-directed small molecule inhibitor: 32 (14.9%) vs 33 (14.4%) Tucatinib: 23 (10.7%) vs 22 (9.6%) Lapatinib: 7 (3.3%) vs 10 (4.4%) Neratinib: 2 (0.9%) vs 0 "Similar proportions of patients in both arms received subsequent anticancer therapies. T-DXd was the preferred first subsequent anti-HER2 therapy in both arms. ~10% of patients received first subsequent regimens containing tucatinib." Source: ESMO Breast 2026 Abstract 423RO, presented by Giuseppe Curigliano, May 8 2026. Tweet capture via @kazuki_nozawa (375 impressions).
Highest-engagement tweets about this trial, ranked by KOL discussant count (replies + quote-tweets). Replies in green, quote-tweets in blue. Wall Street, stock-promo, and non-substantive replies excluded.
@myESMO #ESMOBC26 HER2 Climb 02. TDM1 + tucatinib no OS benefit. PFS better but more toxic. Seems this combo should not move fwd! Tucatinib has better and highly effective settings/combos. @curijoey @OncoAlert https://t.co/gYn1W6pNGD
HER2CLIMB-02 expertly presented by @curijoey T-DM1 +/- tucatinib for HER2+ MBC No difference in overall survival seen Updated PFS analysis confirms benefit ITT PFS 9.5 vs 7.4 mo (HR 0.739) BM PFS: 7.8 vs 5.7 mo (HR 0.608) #ESMOBreast26 @OncoAlert
HER2CLIMB-02 is a Phase III randomized, double-blind, placebo-controlled trial evaluating tucatinib + T-DM1 vs T-DM1 + placebo in patients with previously treated HER2-positive locally advanced or metastatic breast cancer. Primary analysis at SABCS 2023 demonstrated significant PFS improvement with the tucatinib combination. The final OS update presented at ESMO Breast 2026 by Giuseppe Curigliano confirmed continued PFS benefit (including in patients with brain metastases) but did NOT show a statistically significant OS improvement.
Population: Adults with HER2+ unresectable locally advanced or metastatic BC previously treated with trastuzumab and a taxane (in any setting). Brain metastases (treated or untreated, stable) eligible — important for tucatinib's CNS activity.
Interventions: Tucatinib 300 mg PO BID + T-DM1 3.6 mg/kg IV Q21D (or matching placebo + T-DM1). Treatment until progression, unacceptable toxicity, or withdrawal.
Endpoints: Primary: PFS by investigator. Secondary: OS, PFS by BICR, ORR, DoR, PFS in patients with brain metastases, safety.
Updated PFS: median 9.5 months tucatinib+T-DM1 vs 7.4 months control (HR 0.74). Brain metastasis subgroup PFS: 7.8 vs 5.7 months (HR 0.608, per Tolaney live capture). Final OS analysis at data cutoff 10 October 2025 (50.7 months median follow-up): total population median OS 43.3 vs 41.0 months (HR 0.983, 95% CI 0.762–1.269; stratified log-rank p=0.8959). Brain metastasis OS: 35.8 vs 34.4 months (HR 0.886, 95% CI 0.616–1.275; p=0.5146) — also not statistically significant. PFS benefit observed in primary analysis is maintained but did not translate into OS advantage. Confirmed ORR was numerically higher with tucatinib (42.0% vs 36.1%) [Annals Oncol 2025]. Subsequent systemic therapy use was similar between arms (83.7% tucatinib vs 87.8% control); T-DXd was the preferred first subsequent anti-HER2 therapy in both arms [ESMO Breast 2026 423RO, DCO 10 Oct 2025].
Per the Annals of Oncology 2025 primary publication [Annals Oncol 2025], the most common treatment-emergent AEs (tucatinib + T-DM1 vs placebo + T-DM1) were: nausea 65.4% vs 49.4%; diarrhea 56.7% vs 26.6%; fatigue 48.9% vs 37.3%. Grade ≥3 ALT and AST elevations each occurred in 16.5% (n=38) tucatinib vs 2.6% (n=6) control. TEAEs leading to any treatment discontinuation: 22.1% (n=51) tucatinib vs 11.6% (n=27) control. TEAEs leading to death: 1.3% (n=3) tucatinib vs 0.9% (n=2) control. The ESMO Breast 2026 updated safety analysis identified no new signals [ESMO Breast 2026 423RO, DCO 10 Oct 2025]. Tucatinib’s CNS activity (previously established in HER2CLIMB-01) remains a key rationale for evaluating it in HER2+ MBC with brain involvement.
Hope Rugo’s verdict was unambiguous: “HER2 Climb 02. TDM1 + tucatinib no OS benefit. PFS better but more toxic. Seems this combo should not move fwd! Tucatinib has better and highly effective settings/combos.” Sara Tolaney reported the numbers straight: “No difference in overall survival seen. Updated PFS analysis confirms benefit. ITT PFS 9.5 vs 7.4 mo (HR 0.739). BM PFS: 7.8 vs 5.7 mo (HR 0.608).” The OCR-captured conclusion slide confirmed that “the final OS analysis after 50.7 months of follow-up did not show a statistically significant difference between treatment arms,” while the updated PFS analysis “confirmed the benefit of tucatinib + T-DM1 over the control arm in previously treated patients with HER2+ LA/MBC.” KOL volume on this trial was relatively low — Rugo and Tolaney carried most of the interpretive weight, with no public dissenting voice on Rugo’s “should not move fwd” read.
| Handle | Name | Sentiment | Tweet (excerpt) | Imp. |
|---|---|---|---|---|
| @DrRishabhOnco | Dr Rishabh Jain | Neutral | 💊 PFS win. OS flat. HER2CLIMB-02 updated results at #ESMOBreast26 👇 👥 HER2+ MBC | n=463 🧠 Brain mets included 🟢 PFS… | 754 |
| @stolaney1 | Sara Tolaney | Neutral | HER2CLIMB-02 expertly presented by @curijoey T-DM1 +/- tucatinib for HER2+ MBC No difference in overall survival seen … | 685 |
| @DrRishabhOnco | Dr Rishabh Jain | Neutral | #ESMOBreast26 HER2CLIMB-02 update: Tucatinib + T-DM1 improved PFS earlier. But mature OS data are now negative. 🧪 Tuc… | 518 |
| @hoperugo | Hope Rugo | Neutral | @myESMO #ESMOBC26 HER2 Climb 02. TDM1 + tucatinib no OS benefit. PFS better but more toxic. Seems this combo should not … | 500 |
