Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial

Barcenas, CH; Hurvitz, Sara A.; Palma, Jack A. Di; Bose, Ron; Chien, A. Jo; Iannotti, Nicholas; Marx, Gavin; Brufsky, Adam; Litvak, Anya M.; Ibrahim, Emad; Álvarez, Ricardo H.; Ruíz‐Borrego, Manuel; Chan, Nancy; Manalo, Yvonne; Kellum, A; Trudeau, Maureen; Thirlwell, Michael P.; Saenz, J. Garcia; Hunt, Daniel; Bryce, Richard; McCulloch, Leanne; Rugo, Hope S.; Tripathy, Debu; Chan, Arlene; Carcas, Lauren; Castrellon, Aurelio; Chan, Derwin King Chung; Cheong, K. A.; Choi, Byung Ock; Coleman, Michael P.; Conlin, Alison; Dichmann, Robert; Ellison, David M.; Erickson, Nicholette; Gore, Ira; Hansen, Vincent; Db, Huang; Hufnagel, David; Kass, Frederic; Kendall, Stephan D.; Kozloff, Mark; Lawler, W; Nahum, Kenneth; Pistilli, Barbara; Reyes, Eduardo; Seeger, Janell; Somer, Robert A.; Chiu, Elizabeth; Thomas, Gary W.; Tkaczuk, Katherine H.; Vaziri, Irfan; Wade, James L.; Wilkinson, Mary

doi:10.1016/j.annonc.2020.05.012

Cited by 85 publications

(71 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Antidiarrheal prophylaxis or neratinib dose escalation (escalating from 160mg to 240mg over two weeks) have since been shown to reduce the incidence, severity and duration of neratinib-associated grade ≥3 diarrhea in the phase II CONTROL study as compared with ExteNET. 27 The greatest benefits were seen in the dose-escalation cohort of CONTROL, where the rate of grade 3 diarrhea was 15% (vs 40% in ExteNET), the median cumulative duration of grade 3 diarrhea was 2 days (5 days in ExteNET), and the rate of discontinuation due to diarrhea was 3% (17% in ExteNET). 27 Tolerability is also improved with pre-emptive prophylaxis or dose escalation, 27 allowing many patients to complete the full year of neratinib treatment.…”

Section: J O U R N a L P R E -P R O O F Discussionmentioning

confidence: 97%

“…Current clinical practice in some countries may involve the use of two additional HER2-directed agents (pertuzumab 7 and trastuzumab emtansine 9 ) prior to receiving extended adjuvant therapy with neratinib, which differs from the patient population in ExteNET. While the precise implications of changing clinical practice on the findings from ExteNET are not known, several studies have demonstrated the efficacy and safety of neratinib-based regimens after pertuzumab and/or trastuzumab emtansine, 23,24,27 or neratinib in combination with trastuzumab emtansine. 28 Moreover, due to the mechanism of action of neratinib, which differs from the above therapies -namely inhibition of the intracellular component of the HER2 pathway -neratinib represents a potentially non-cross-resistant therapy.…”

Section: J O U R N a L P R E -P R O O F Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial

Chan

Moy

Mansi

et al. 2021

Clinical Breast Cancer

171

130

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Section: J O U R N a L P R E -P R O O F Discussionmentioning

confidence: 97%

Section: J O U R N a L P R E -P R O O F Discussionmentioning

confidence: 99%

Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial

Chan

Moy

Mansi

et al. 2021

Clinical Breast Cancer

171

130

View full text Add to dashboard Cite

show abstract

“…Compared with the overall population, treatment-related diarrhea leading to treatment discontinuation was slightly lower in the Asian cohort treated with N + C (1% vs 2.6%) [22]. Alternatively, neratinib tolerability may be further improved with strategies including preemptive prophylaxis with loperamide + budesonide, loperamide + colestipol, and the incorporation of a step-wise dose escalation to the starting dose [39].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Pan-Asian Subgroup of patients in the NALA Trial: A Randomized Phase III NALA Trial Comparing Neratinib + Capecitabine (N+C) vs Lapatinib + Capecitabine (L+C) in Patients with HER2+ Metastatic Breast Cancer (mBC) Previously Treated with Two or more HER2-Directed Regimens

Dai

Yin

Chen

et al. 2021

Preprint

View full text Add to dashboard Cite

Purpose: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+ breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib + capecitabine (N+C) against lapatinib + capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein.Methods: 621 centrally-assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240mg qd) + C (750mg/m2 bid, day 1-14) with loperamide prophylaxis, or to L (1250mg qd) + C (1000mg/m2 bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally-assessed progression free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety.Results: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P=0.0014), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P=0.039). Both median OS (23.8 versus 18.7 months; P=0.185) and DoR (11.1 versus 4.2 months; P<0.0001) were extended with N+C, compared to L+C. Diarrhea was the most frequent treatment-emergent adverse event (TEAE) in both arms (78.8 versus 51.0%). The incidence of grade 3/4 TEAEs and TEAEs leading to treatment discontinuation was comparable between the two arms.Conclusion: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. Clinical Trial Registration: NCT01808573

show abstract

“…Small molecule inhibitors continue to be utilised and developed, including neratinib [63]. This is a pan-HER irreversible tyrosine kinase inhibitor approved for extended adjuvant treatment in HER2+ breast cancer patients.…”

Section: Next Generation Treatmentsmentioning

confidence: 99%

HER2 splice variants in breast cancer: investigating their impact on diagnosis and treatment outcomes

et al. 2020

View full text Add to dashboard Cite

Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial

Cited by 85 publications

References 9 publications

Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial

Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial

Analysis of the Pan-Asian Subgroup of patients in the NALA Trial: A Randomized Phase III NALA Trial Comparing Neratinib + Capecitabine (N+C) vs Lapatinib + Capecitabine (L+C) in Patients with HER2+ Metastatic Breast Cancer (mBC) Previously Treated with Two or more HER2-Directed Regimens

HER2 splice variants in breast cancer: investigating their impact on diagnosis and treatment outcomes

Contact Info

Product

Resources

About