Ado-Trastuzumab Emtansine (T-DM1) in HER2+ Advanced Breast Cancer Patients: does Pretreatment with Pertuzumab Matter?

Fabi, Alessandra; Giannarelli, Diana; Moscetti, Luca; Santini, Daniele; Zambelli, Alberto; Laurentiis, Michelino De; Caruso, Michele; Generali, Daniele; Valle, Elisabetta Della; Leonardi, V.; Cannita, Katia; Arpino, Grazia; Filippelli, Gianfranco; Ferretti, Gianluigi; Giampaglia, Marianna; Montemurro, Filippo; Nisticò, Cecilia; Gasparro, Simona; Cognetti, Francesco

doi:10.2217/fon-2017-0336

Cited by 25 publications

(26 citation statements)

References 12 publications

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“…However, other real-world studies have suggested inferior outcomes for patients treated with TE after pertuzumab exposure compared with pertuzumab-naïve patients. In a study by Fabi et al, 27 34 patients with prior trastuzumab/pertuzumab had significantly worse PFS compared with 73 patients with prior trastuzumab only (5 vs 11 months). In a multicenter, Italian cohort of 250 patients, PFS and OS were numerically less for patients with prior trastuzumab/pertuzumab in comparison to patients with prior trastuzumab only.…”

Section: Discussionmentioning

confidence: 95%

Pertuzumab and Trastuzumab Emtansine for Human Epidermal Growth Factor Receptor-2–Positive Metastatic Breast Cancer: Contemporary Population-Based Outcomes

Lupichuk¹,

Cheung²,

Stewart³

2019

Breast Cancer�(Auckl)

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Background: Real-world outcomes for patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) treated with pertuzumab in combination with taxane chemotherapy plus trastuzumab (TaxTP) in the first line setting and trastuzumab emtansine (TE) in any line of treatment are lacking. Methods: Cohorts of patients treated with (1) TaxTP and (2) TE from January 1, 2013 through December 31, 2016 were retrospectively obtained from a population-based database. Cohorts were described according to age, hormone receptor (HR) status, prior systemic therapies, event-free survival (EFS) defined as time from start of treatment to start of next line of treatment or death, and overall survival (OS). Results: A total of 122 patients were treated with TaxTP and 104 with TE. In the TaxTP cohort, EFS was significantly longer in the trastuzumab-naïve group compared with the adjuvant trastuzumab group (median EFS = 27.0 vs 12.4 months; P = .002). In the TaxTP cohort, median OS was not reached. In the TE cohort, EFS was significantly longer in the pertuzumab-naïve group compared with pertuzumab-exposed group (median time to treatment failure [TTF] = 18.7 vs 5.5 months; P < .001). Overall survival was also significantly longer in the pertuzumab-naïve group compared with the pertuzumab-exposed group (median OS = 23.2 vs 14.1 months; P = .022). In multivariable analyses, adjuvant trastuzumab and prior pertuzumab exposure in the metastatic setting remained significant predictors of inferior EFS for patients treated with TaxTP and TE, respectively. Conclusions: New anti-HER2 therapies appear to be clinically relevant in the real-world.

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Section: Discussionmentioning

confidence: 95%

Pertuzumab and Trastuzumab Emtansine for Human Epidermal Growth Factor Receptor-2–Positive Metastatic Breast Cancer: Contemporary Population-Based Outcomes

Lupichuk¹,

Cheung²,

Stewart³

2019

Breast Cancer�(Auckl)

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Section: Discussionmentioning

confidence: 99%

“…There were two other retrospective studies conducted in Italy, which compared PFS of T-DM1 between patients who had received Pmab and those without Pmab exposure [ 13 , 14 ]. They also showed the shorter duration of PFS in patients who had received Pmab in second line treatment (3 months [95% CI 2–4 months] vs. 8 months [95% CI 4–12 months] [ 13 ] and 5.0 months [95% CI 4.3–5.7 months] vs. 11.0 months [95% CI 7.8–14.2 months] [ 14 ]). The study reported by Fabi et al [ 14 ] provided propensity score-matched sample with perfect match for age and PFS at first-line, and it also showed a shorter PFS in patients treated with Pmab (5.0 months [95% CI 4.3–5.7 months] vs. 11.0 months [95% CI 7.3–14.0 months]).…”

Section: Discussionmentioning

confidence: 99%

“…They also showed the shorter duration of PFS in patients who had received Pmab in second line treatment (3 months [95% CI 2–4 months] vs. 8 months [95% CI 4–12 months] [ 13 ] and 5.0 months [95% CI 4.3–5.7 months] vs. 11.0 months [95% CI 7.8–14.2 months] [ 14 ]). The study reported by Fabi et al [ 14 ] provided propensity score-matched sample with perfect match for age and PFS at first-line, and it also showed a shorter PFS in patients treated with Pmab (5.0 months [95% CI 4.3–5.7 months] vs. 11.0 months [95% CI 7.3–14.0 months]). However, all institution involved in the previous three retrospective studies were in Western countries, and our study was the first to compare the outcomes between patients who had previously received Pmab and patients without Pmab exposure in Asian population.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of the efficacy of trastuzumab emtansine between patients with metastatic human epidermal growth factor receptor 2-positive breast cancers previously treated with combination trastuzumab and pertuzumab and with trastuzumab only in Japanese population

Noda-Narita¹,

Shimomura²,

Kawachi³

et al. 2019

Breast Cancer

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Background Trastuzumab emtansine (T-DM1) has been approved since 2013 for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) who had received trastuzumab (Tmab) and taxane. However, no clinical trial has evaluated the efficacy of T-DM1 in those who have previously received pertuzumab (Pmab). This study aimed to compare the efficacy of T-DM1 between patients who had received Tmab and Pmab and those who had received Tmab only in Japanese population. Methods We identified all patients with HER2-positive MBC who received T-DM1 between April 1, 2014 and February 28, 2017 in our institution. The patients were divided into the Tmab group (i.e., those who received only Tmab before T-DM1 treatment) and the Tmab/Pmab group (i.e., those who received Tmab and Pmab before T-DM1 treatment), and progression-free survival (PFS) and best response were compared between the two groups. Results A total of 42 patients were enrolled for outcome analysis. The median follow-up period was 4.8 months, and the median number of prior chemotherapy regimens for metastatic disease before T-DM1 was 1 (range 1–2) in the Tmab/Pmab group and 2 (range 0–6) in the Tmab group. The median PFS was 2.8 months in the Tmab/Pmab group (95% confidence interval [CI] 1.7–4.8 months) and 7.8 months in the Tmab group (95% CI 5.5–15.9 months) ( p = 0.0030). The best response was lower in the Tmab/Pmab group (11.1% vs. 25.0%). Conclusions Patients with HER2-positive MBC who received Tmab and Pmab treatment before T-DM1 have fewer benefits from T-DM1.

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“…In post hoc analysis of T-DXd, previous pertuzumab use did not affect the results either [17]. But the possibility that treatment after pertuzumab can be less effective has been suggested [18][19][20], though it was based on small and observational studies examining the efficacy of T-DM1 in patients with previous pertuzumab. Thus, further investigation is warranted to evaluate the influence of previous pertuzumab use over post-T-DM1 treatment.…”

Section: Discussionmentioning

confidence: 99%

Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B)

et al. 2021

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Background Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. Methods In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1–28.0], DCR = 66.6% (95% CI 60.8–72.0), median PFS = 6.1 months (95% CI 5.3–6.7), median TTF = 5.1 months (95% CI 4.4–5.6), and median OS = 23.7 months (95% CI 20.7–27.4). Conclusion The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

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Ado-Trastuzumab Emtansine (T-DM1) in HER2+ Advanced Breast Cancer Patients: does Pretreatment with Pertuzumab Matter?

Abstract: Patients treated with T-DM1 who previously received pertuzumab present poorer clinical outcomes compared with those receiving a trastuzumab-only-based regimen in the first-line setting.

Cited by 25 publications

References 12 publications

Pertuzumab and Trastuzumab Emtansine for Human Epidermal Growth Factor Receptor-2–Positive Metastatic Breast Cancer: Contemporary Population-Based Outcomes

Pertuzumab and Trastuzumab Emtansine for Human Epidermal Growth Factor Receptor-2–Positive Metastatic Breast Cancer: Contemporary Population-Based Outcomes

Comparison of the efficacy of trastuzumab emtansine between patients with metastatic human epidermal growth factor receptor 2-positive breast cancers previously treated with combination trastuzumab and pertuzumab and with trastuzumab only in Japanese population

Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B)

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