From Capecitabine to Tucatinib: Data Reveal New Treatment Options for Patients

Pharmacy Practice in Focus: OncologyJanuary 2024
Volume 6
Issue 1

Significant study results could inform clinical practice strategies.

Key trial results that may shape clinical practice in breast cancer were presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) in Texas in December. Following are some highlights.

Woman holding a pink ribbon for breast cancer awareness

Image credit: lovelyday12 |

Tucatinib Plus Trastuzumab Emtansine Improves Progression-Free Survival in HER2+ Metastatic Breast Cancer

Findings from the phase 3 HER2CLIMB-02 trial (NCT03975647) showed that the combination of HER2- targeting treatments tucatinib (Tukysa; Seagen) and trastuzumab emtansine (T-DM1, Kadcyla; Genentech) improved progression-free survival (PFS) when compared with T-DM1 alone in patients with previously managed unresectable locally advanced or metastatic HER2- positive (HER2+) breast cancer. Results of a phase 1b study (NCT01983501) published in 2018 had shown that tucatinib plus T-DM1 demonstrated encouraging antitumor activity, including intracranial responses. Tucatinib in combination with trastuzumab plus capecitabine was approved by the FDA on April 17, 2020, for patients who have received 1 or more prior anti-HER2–based regimens in the metastatic setting, including patients with brain metastases, based on results from the phase 2 HER2CLIMB trial (NCT02614794).

In the current trial, the interim overall survival (OS) results remain immature at a median follow-up of 24.4 months, with a 24.1% decrease in risk for progression or death in patients receiving tucatinib. The median PFS (mPFS) was 9.5 months in the tucatinib/T-DM1 group and 7.4 months in the control group. For patients with brain metastases, mPFS was 7.8 months in the tucatinib/T-DM1 cohort and 5.7 months in the control group.1,2

Updated Ribociclib Invasive Disease-Free Survival Data

Analysis of the final phase 3 NATALEE trial (NCT03701334) of invasive disease–free survival (IDFS) with adjuvant ribociclib (Kisqali; Novartis) plus a nonsteroidal aromatase inhibitor (AI) vs a nonsteroidal AI alone in patients with early-stage hormone receptor–positive (HR+), HER2-negative (HER2–) breast cancer was presented at the conference. Adding ribociclib to an AI after surgery reduced the risk of invasive disease occurrence or death by 25.1% in patients with early-stage HR+, HER2– breast cancer. In the updated analysis, ribociclib improved IDFS by 27.7% in patients with nodenegative disease. These updated data from the NATALEE trial will form the basis of a submission to the FDA for ribociclib as an adjuvant treatment.3

Skipping Radiation in Neoadjuvant Chemotherapy

Findings from the NRG Oncology/NSABP-B-51/RTOG 1304 clinical trial (NCT01872975) demonstrated that for patients whose breast cancer converted from lymph node–positive disease to lymph node–negative disease after neoadjuvant chemotherapy, skipping adjuvant regional nodal irradiation (RNI) did not increase the risk of disease recurrence or death 5 years after surgery. During the trial, more than 1500 patients had similar outcomes whether they received adjuvant RNI or not: 91.8% of patients in the no RNI arm and 92.7% of those in the RNI arm were free of invasive breast cancer recurrences 5 years after surgery. Distant recurrence and OS rates were also similar between the arms, with 93.4% of patients in each arm free from distant recurrence 5 years after surgery and 94% of those in the no RNI arm and 93.6% of those in the RNI arm alive after 5 years.4

A Potential Second TROP2 Antibody-Drug Conjugate in HR+/HER2– MBC

In patients with previously managed HR+, HER2– or HER2-low metastatic breast cancer (MBC), updated results from the TROPION-Breast01 trial (NCT05104866) confirmed earlier benefits were seen with datopotamab deruxtecan (Dato-DXd; AstraZeneca, Daiichi Sankyo Inc). Eligible patients with HER2– or HER2-low disease had more than 2 prior lines of chemotherapy and had experienced disease progression with prior endocrine therapy and inoperable/metastatic disease. The mPFS for patients receiving Dato-DXd in the phase 3 trial was 6.9 months compared with 4.5 months for those receiving investigator’s choice of chemotherapy, with options including eribulin mesylate (Halaven; Eisai), vinorelbine (Navelbine; Pierre Fabre Pharmaceuticals), gemcitabine (Gemzar; Eli Lilly and Company), or capecitabine (Xeloda; Genentech). The other TROP2 antibody-drug conjugate (ADC), sacituzumab govitecan (Trodelvy; Gilead Sciences), was approved earlier this year.5

Novel Targeted Therapy for Heavily Pretreated Patients

Data on tinengotinib for heavily premanaged metastatic HR+, HER2– breast cancer or triple-negative breast cancer (TNBC) demonstrated clinical benefit with manageable adverse events (AEs) either alone or in combination with nab-paclitaxel (Abraxane; Bristol Myers Squibb). With tinengotinib alone, overall response rate was reported at 45.5% and 23.5% in HR+, HER2– breast cancer and TNBC, respectively, with an mPFS of 5.68 and 2.73 months, respectively. Partial responses were seen in 3 patients designated as having HER2-zero disease and in 2 patients designated as having HER2-low disease. The most common treatment-related AEs seen with tinengotinib monotherapy were hypertension (60%), stomatitis (50%), palmar-plantar erythrodysesthesia syndrome (46.7%), and diarrhea (20%).6

Fibroblast Growth Factor Receptor Inhibitor Data

Findings from the phase 2 FOENIX-MBC2 trial (NCT04024436) demonstrated early signs of antitumor activity when combining the fibroblast growth factor receptor (FGFR) inhibitor futibatinib (Lytgobi; Taiho Oncology Inc) with fulvestrant (Faslodex; AstraZeneca) in patients with advanced HR+, HER2– breast cancer harboring high-level FGFR1 amplification. Patients had a median age of 58 years and a median of 3 lines of any prior systemic anticancer therapy and had received previous CDK4/6 inhibitor treatment. The most common treatment-related AEs were hyperphosphatemia (95.5%), alopecia (54.5%), constipation (45.5%), and dry mouth (40.9%).6

Biomarker Testing and Therapy Selection

The ADCs fam-trastuzumab deruxtecan-nxki (T-DXd, Enhertu; Daiichi Sankyo Inc) and sacituzumab govitecan are approved by the FDA to treat patients with MBC. However, their efficacy often depends on target expression, and the best method for measuring expression is not known. According to findings presented by Robbins et al at SABCS, a novel selective biomarker tool (Troplex) may help select the ADC therapy that would be most effective in patients with MBC. In the new study, researchers used quantitative immunofluorescence to assess levels of HER2, TROP2, and cytokeratin across hundreds of MBC cases. The researchers discovered that most of the cases demonstrated high levels of either HER2 or TROP2. The researchers hope their new findings can provide valuable clinical data to clinicians selecting between T-DXd and sacituzumab govitecan.7


1. Symposium overview. 2023. Accessed December 8, 2023.

2. Tallent A. Tucatinib, ADC combo boosts PFS in advanced HER2-positive breast cancer.OBR Oncology. December 7, 2023. Accessed December 7, 2023.

3. Liu A. SABCS: as Lilly showdown nears, Novartis gives another look at Kisqali data in early breast cancer. Fierce Pharma. December 8, 2023. Accessed December 8, 2023.

4. Neoadjuvant chemotherapy may help some patients with breast cancer skip regional nodal irradiation. ASCO Post. December 6, 2023. Updated December 8, 2023. Accessed December 20, 2023.

5. Ray T. Dato-DXd phase III data shows promising efficacy, safety profile in competitive breast cancer market. Precision Medicine Online. December 7, 2023. Accessed December 8, 2023.

6. Novel targeted therapies may benefit patients with metastatic hormone receptor–positive/HER2-negative breast cancer. ASCO Post. December 7, 2023. Updated December 8, 2023. Accessed December 10, 2023.

7. Novel selective biomarker tool may help select effective targeted therapies in patients with metastatic breast cancer. ASCO Post. December 7, 2023. Updated December 8, 2023. Accessed December 10, 2023.

About the Author

Douglas Braun, PharmD, CSP, RPh, is a senior pharmacy director at the American Oncology Network, LLC, in Naples, Florida.

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