Author(s): Vikas Ostwal, MD, DM1, Sarika Mandavkar, BSc1, Prabhat Bhargava, MD, DM1, Sujay Srinivas, MD, DM1, Akhil Kapoor, MD, DM2, Omshree Shetty, PhD3, Sadhana Kannan, MSc4, Deepali Chaugule, BSc1, Rajshree Patil, BSc1, Manali Parulekar, BSc1, Chaitali Nashikkar, BHMS5, Suman Kumar Ankathi, MD6, Akshay Dwarka Baheti, MD6, Daksha Mehta, MD6, Rajiv Kumar Kaushal, MD7, Subhash Yadav, MD7, Aekta Shah, MD7, Shraddha Patkar, MS, MCh8, Mahesh Goel, MS, Anant Ramaswamy, MD, DM9
PURPOSE
Human epidermal growth factor receptor 2 (HER2) overexpression is seen in 4%-16% of biliary tract cancers (BTCs). We aimed to evaluate the clinical activity of gemcitabine-cisplatin (GC) plus anti-HER2 antibody trastuzumab as initial treatment in HER2-positive BTCs.
METHODS
This study was an investigator-initiated, open-label, single-arm, multi-institutional, phase II trial in adult patients with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+ and fluorescent in situ hybridization–positive), treatment-naïve BTCs. The primary end point of the study was 6-month progression-free survival (PFS). Next-generation sequencing was performed on tissue samples to evaluate mutational status.
RESULTS
From March 2020 to August 2022, of the 876 screened patients, 118 (13.4%) were found to have HER2-positive status, of whom 90 were enrolled in the study. Most patients had GBC (n = 96; 96%) with two or more sites of metastatic disease (n = 70; 78%). With a median follow-up of 17.3 (95% CI, 15.22 to 19.32) months, 72 patients had disease progression with a median PFS of 7 (95% CI, 6.2 to 7.8) months. The diagnosis to event 6-month PFS rate was 75.6% (95% CI, 66.6 to 84.6). A complete or partial response was seen in 50 (55.5%) patients and 22 (24.4%) patients had stable disease as the best response to treatment, for an overall disease control rate of 80%. The presence of isolated TP53 mutations was associated with inferior PFS compared with other mutations (TERT promoter, HER2, PIK3CA, etc) or no detected mutations (6.51 v 12.02 v 10.58 months; P < .001).
CONCLUSION
The combination of GC and trastuzumab achieved its primary end point of improving PFS compared with historical data in the treatment-naïve HER2-positive BTC. Evaluating additional mutations such as TP53 and PIK3CA along with HER2 testing may help to preferentially select patients for anti-HER2 therapy in the future (Clinical Trial Registry India number: CTRI/2019/11/021955).
Author Affiliations
1Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India, 2Department of Medical Oncology, Homi Bhabha Cancer Hospital, Varanasi, India, 3Department of Molecular Oncology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India, 4Department of Statistics, Advanced Centre for Treatment, Research and Education in Cancer, Homi Bhabha National Institute (HBNI), Mumbai, India, 5Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India, 6Department of Radiology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India, 7Department of Pathology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India, 8Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, India, 9Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, India
