Abstract
To evaluate the efficacy of triplet chemotherapy (gemcitabine, cisplatin, and nab-paclitaxel) to the standard of care in locally advanced or metastatic gall bladder cancer. A total of 60 patients with locally advanced (unresectable) and metastatic gall bladder cancer were randomized to either of the 2 arms. Arm A received two drugs gemcitabine and cisplatin and arm B received three drugs gemcitabine, cisplatin and nab-paclitaxel. The evaluation was done post 3 and 6 cycles of chemotherapy. Patients were then followed up every 6 months for 2 years to assess response rates (RR), progression-free survival (PFS), and overall survival (OS). The combination of gemcitabine and cisplatin (arm A) had an overall response rate of 13.3% whereas it was 61.9% in patients who received gemcitabine, cisplatin, and nab-paclitaxel (0.004). The median progression-free survival for patients who received gemcitabine and cisplatin was 4.5 months (95% CI, 4.0-4.9) compared to 7.6 months (95% CI, 3.9–11.2) for patients treated with gemcitabine, cisplatin, and nab-paclitaxel (p ≤ 0.05). There was no increase in grade 3 adverse events with the addition of nab-paclitaxel. This study showed promising results, with triplet chemotherapy having a significantly better overall response rate and median progression-free survival.
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-026-36231-9.
Keywords: Doublet therapy, Gall bladder cancer, Locally advanced, Metastatic, Triplet therapy
Subject terms: Cancer, Oncology
Introduction
Biliary tract cancer (BTC) includes gall bladder cancer (GBC) as well as intrahepatic and extrahepatic cholangiocarcinoma. GBC is the most common malignancy among biliary tract cancers1.
In 2022, there were an estimated 122,469 new cases of gall bladder cancers and 89,045 deaths worldwide2. GBC accounts for about 1.3% of total cancer incidence and 1.7% of total cancer- related deaths globally3.
India has a high incidence of GBC, contributing approximately 10% (21,780 cases) of the global burden4. According to a study by Dutta et al., the ASR (age standardised rate) for Indian women with GBC is 11.8 per 100,000 population in northern India and 17.1 per 100,000 in north-eastern India5.
GBC may be diagnosed preoperatively, intraoperatively during surgical exploration for abdominal symptoms attributed to another disease process, or postoperatively upon histopathological examination of the gallbladder specimen - typically removed during cholecystectomy for symptomatic cholelithiasis. The majority of patients present at later stages, with a poor prognosis6. This poor prognosis is primarily due to the asymptomatic nature of the disease, making early diagnose difficult. A majority (60%–70%) of patients in India present with Stage IV disease, and approximately one‑third have metastatic disease (Stage IVB) at presentation7–9.
Doublet chemotherapy with gemcitabine and cisplatin has been the standard of care for metastatic GBC for over a decade10,11. Recently, TOPAZ 112 and KEYNOTE 96613 studies have shown a survival benefit with the addition of durvalumab or pembrolizumab, respectively, to the chemotherapy backbone in patients with locally advanced/metastatic BTC.
In a phase II trial conducted by Shroff et al., patients with metastatic BTC were treated with a triplet regimen consisting of gemcitabine, nab- paclitaxel and cisplatin. This triplet combination has shown a good response rate, with improved overall survival and progression-free survival among patients14. The authors presented the updated results of their phase III trial SWOG 1815 in ASCO 2023, where they concluded that the triplet combination did not result in a statistically significant improvement in median overall survival (OS) when compared to the doublet regimen. However, in a subset analysis, patients with locally advanced disease and those with GBC had a median OS benefit15.
Studies from the Indian subcontinent have lacked data on the treatment of patients with metastatic GBC. While there have been reports and articles discussing the complexity of the disease, none have explored the use of the triplet regimen in patients with locally advanced or metastatic gall bladder cancer7.
Therefore, this study aimed to evaluate the efficacy of the triplet regimen in Indian patients with metastatic and locally advanced (unresectable) GBC. We hypothesized that the triplet regimen would be more efficacious than the doublet regimen in Indian patients with GBC. This study aims to provide real-world evidence from a high-incidence region, offering insights into treatment outcomes for metastatic or locally advanced GBC that may inform management strategies in other populations facing similar disease patterns globally.
Methodology
Study design and patients
We conducted an open-label, single-center, phase II randomized controlled trial at Indraprastha Apollo Hospital, Delhi, India, from December 2019 to December 2021, in adults with newly diagnosed locally advanced (unresectable) and metastatic gallbladder cancer.
Inclusion criteria were: (1) locally advanced GBC deemed unresectable by a surgical oncologist and (2) histologically and radiologically confirmed metastatic gallbladder cancer, diagnosed via contrast-enhanced CT scan of the chest, abdomen, and pelvis; MRI of the abdomen and pelvis with CECT chest; or whole-body PET CT scan. Eligible patients had an ECOG performance status of 0–2 and adequate organ function, including renal function (CrCl > 60 mL/min), hepatic function (serum bilirubin < 1.5× ULN, SGOT/SGPT < 10× ULN), and haematological parameters (Hb > 8 g/dL, platelet count > 100,000/µL, ANC > 1500/µL). Patients were excluded if they had received prior systemic chemotherapy for their current malignancy.
The study was approved by Institutional Ethics Committee – Biomedical Research of Indraprastha Apollo Hospitals, New Delhi (Registration No.-EC /NEW/INST/2020/567). All methods were performed in accordance with the relevant guidelines and regulations. Written informed consent was obtained from all patients. The trial was conducted in line with the Declaration of Helsinki and Good Clinical Practice (GCP) Guidelines. It was registered with the Clinical Trials Registry—India (CTRI) on 09/09/2021 (registration number: CTRI/2021/09/036362).
Randomisation
Patients were randomized (using online computer- generated random number tables) into two arms after imaging and biopsy as depicted in Fig. 1.
Fig. 1.
Flow chart showing allocation of participants to each treatment arm and the corresponding drug regimens. *Contrast-enhanced CT scan of chest, abdomen, and pelvis / MRI abdomen and pelvis with CECT chest /whole-body PET CT scan.
Arm A received gemcitabine (1000mg/m2 IV) and cisplatin (25mg/m2 IV) on Days 1 and 8 of the 21-day cycle.
Arm B received a triplet regimen of gemcitabine (1000 mg/m2), cisplatin (25 mg/m2), and nab-paclitaxel (125 mg/m2) IV on Days 1 and 8 of the 21-day cycle.
Treatment response was assessed using RECIST v.1.1 or PERCIST 1.0 criteria16 after 3 and 6 cycles of chemotherapy. Patients were followed up every 6 months for 2-years to assess the primary and secondary endpoints.
Endpoints
The primary endpoint was the Overall Response Rate (ORR), defined as the sum of complete and partial response rates based on radiological assessment using either RECIST 1.1 or PERCIST 1.0 criteria (For Definitions See Supplementary File).
According to RECIST 1.1 (Response Evaluation Criteria in Solid Tumors), progressive disease is defined as at least a 20% increase in the sum of diameters of up to five target lesions (maximum of two per organ), using the smallest sum on study, with an absolute increase of at least 5 mm, or the appearance of new lesions. A complete response (CR) is the disappearance of all target lesions, while a partial response (PR) is defined as at least a 30% decrease in the sum of the diameters of target lesions. Stable disease (SD) is defined as not meeting the criteria for either PR or progressive disease16.
According to PERCIST 1.0, a complete metabolic response (CMR) is the disappearance of all FDG-avid lesions. A partial metabolic response (PMR) is defined as a ≥ 30% decrease in SULpeak (standardized uptake value peak) and an absolute decline of ≥ 0.8 SUL. Progressive metabolic disease (PMD) is defined as a ≥ 30% increase in SULpeak and an increase of > 0.8 SUL, or the appearance of new lesions. Stable metabolic disease (SMD) is defined as not meeting the criteria for PMR or PMD16.
Secondary endpoints
Secondary endpoints included progression-free survival (PFS) and overall survival (OS). (For Definitions See Supplementary File)
Treatment-related adverse events were classified using the Medical Dictionary for Regulatory Activities, version 23.0, and graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE), version 4.017.
Statistical methods
Results were tabulated in Microsoft Excel. Quantitative data were presented as minimum and maximum values, and as mean ± standard deviation (SD). Qualitative data were summarized using frequency and percentage, separately for each group.
Statistical significance for quantitative variables between the two groups was assessed using the unpaired t-test or the non-parametric Mann–Whitney U test, as appropriate. For qualitative variables, the Chi-square test or Fisher’s exact test was used. A p-value of < 0.05 was considered statistically significant.
Statistical analysis for correlations between clinical/laboratory features and treatment outcomes was performed using SPSS version 24.018.
Sample size calculation
It was calculated using the formula,
 |
Where.
Zα/2 is the critical value at α/2 (e.g. for (e.g., 1.96 for a 95% confidence level).
Zβ is the critical value at β (e.g., 0.84 for 80% power).
p1 and p2 are the expected overall response rates in the two groups.
Based on previous data, the overall response rate with doublet therapy (gemcitabine and oxaliplatin) was estimated at 4.3% (p1), according to André et al.19. The ORR for triplet therapy (gemcitabine, cisplatin, and nab-paclitaxel) was estimated at 40% (p2), as reported by Shroff et al.14.
Using this formula, the minimum required sample size was 18 patients per arm (36 total). However, 60 patients were enrolled in the study to strengthen the analysis.
Results
A total of 60 patients were enrolled, of whom 54 were randomized to receive either doublet therapy (gemcitabine and cisplatin) or triplet therapy (gemcitabine, cisplatin, and albumin-bound paclitaxel). Patients were followed until the data cut-off in December 2021 (Fig. 2).
Fig. 2.
CONSORT diagram illustrating patient enrolment, randomization, and analysis.
The median follow-up duration for the overall study population was 13.2 months (range: 1.9–24.4 months). The median follow-up duration was 6.15 months in Arm A and 13.2 months in Arm B.
All baseline characteristics were well matched between the two arms, and there was no significant difference in age, sex, performance status, BMI, and stage between two arms of treatment (Table 1).
Table 1.
Demographic profile of patients in the doublet therapy (ARM A) and the triplet therapy (ARM B).
| ARM | Total (N;%) | p-value | |||
|---|---|---|---|---|---|
| A (N;%) | B(N;%) | ||||
| Age (years) | ≤ 40 | 2 (7.4) | 4 (14.8) | 6 (11.1) | 0.370 |
| 41–50 | 9 (33.3) | 7 (25.9) | 16 (29.6) | ||
| 51–60 | 6 (22.2) | 9 (33.3) | 15 (27.7) | ||
| 61–70 | 5 (18.5) | 6 (22.2) | 11 (20.3) | ||
| 71–80 | 5 (18.5) | 1 (3.7) | 6 (11.1) | ||
| Sex | Males | 12 (44.4) | 10 (37) | 22 (40.7) | 0.580 |
| Females | 15 (55.5) | 17 (62.9) | 32 (59.3) | ||
| BMI (kg/m2) | < 18.5 | 5 (18.5) | 5 (18.5) | 10 (18.5) | 1.000 |
| 18.5–22.9 | 5 (18.5) | 9 (33.3) | 14 (25.9) | 0.214 | |
| 23–24.9 | 7 (25.9) | 4 (14.8) | 11 (20.3) | 0.311 | |
| 24–24.9 | 10 (37.0) | 9 (33.3) | 19 (35.1) | 0.776 | |
| ECOG PS | 0 | 7 (25.9) | 11 (40.7) | 18 (33.3) | 0.257 |
| 1 | 16 (59.2) | 15 (55.5) | 31 (57.4) | ||
| 2 | 4 (14.8) | 1 (3.7) | 5 (9.2) | ||
| Stage | III | 5 (18.5) | 7 (25.9) | 12 (22.2) | 0.513 |
| IV | 22 (81.4) | 20 (74.0) | 42 (77.7) | ||
| h/o gallstones | Yes | 8 (29.6) | 11 (40.7) | 19 (35.2) | 0.393 |
| No | 19 (70.3) | 16 (51.2) | 35 (64.8) | ||
| Obesity | Yes | 10 (37) | 9 (33.3) | 19 (35.2) | 0.776 |
| No | 17 (62.9) | 18 (66.6) | 35 (64.8) | ||
| No. of cycles | 1 | 1 (3.7) | 1 (3.7) | 2 (3.7) | 1 |
| 2 | 1 (3.7) | 2 (7.4) | 3 (5.5) | 0.64 | |
| 3 | 8 (29.6) | 3 (11.1) | 11 (22.2) | 0.036 | |
| 4 | 2 (7.4) | 0 | 2 (3.7) | 0.49 | |
| 6 | 15 (55.5) | 21 (77.7) | 36 (64.8) | 0.046 | |
| Dose reduction | Yes | 6 (22.2) | 14 (51.8) | 20 (37.0) | 0.024 |
| No | 21 (77.7) | 13 (48.1) | 34 (62.9) | ||
Response assessment using RECIST 1.1 or PERCIST criteria was performed after completion of 3 and 6 cycles of chemotherapy as shown in Table 2.
Table 2.
Response assessment after 3 & 6 cycles of chemotherapy in arm A & arm B.
| Parameters | Arm A (N;%) | Arm B (N;%) | Total | p-value | |
|---|---|---|---|---|---|
| Response post 3 cycles | CR | 1 (4) | 6 (25) | 7 (14.2) | 0.036 |
| PR | 5 (20) | 13 (52) | 18 (36.7) | 0.013 | |
| SD | 9 (36) | 2 (8) | 11 (22.4) | 0.02 | |
| PD | 10 (40) | 3 (12) | 13 (26.5) | 0.029 | |
| Response post 6 cycles | CR | 0 | 5 (23.8) | 5 (13.8) | 0.042 |
| PR | 2 (13.3) | 8 (38) | 10 (27.7) | 0.102 | |
| SD | 7 (46.6) | 5 (23.8) | 12 (33.3) | 0.15 | |
| PD | 6 (40) | 3 (14.2) | 9 (25) | 0.079 | |
After three cycles, response assessment was completed for 49 patients (25 in Arm A and 24 in Arm B). Two patients in the doublet arm and three in the triplet arm were lost to follow-up at the time of interim assessment. At this point, the overall response rate (ORR: complete response + partial response) was 24% in Arm A (6/25) versus 79% in Arm B (19/24). This difference was statistically significant (p < 0.001), as shown in Table 3.
Table 3.
Overall response rate post 3 cycles & post 6 cycles of chemotherapy in arm A & arm B.
| Parameters | Arm A (N;%) | Arm B (N;%) | Total (N;%) | p-value |
|---|---|---|---|---|
| Overall response rate post 3 cycles | 6 (24) | 19 (79) | 25 (51) | < 0.001 |
| Overall response rate post 6 cycles | 2 (13.3) | 13 (61.9) | 15 (41.6) | 0.004 |
After six cycles, response assessment was completed for 36 patients (15 in Arm A and 21 in Arm B). In Arm A, 10 patients showed disease progression after three cycles and were shifted to second-line chemotherapy. In Arm B, 3 patients progressed after three cycles. At the final assessment (after six cycles), the ORR was 13.3% in Arm A (2/15) compared to 61.9% in Arm B (13/21). This difference was also statistically significant (p = 0.004), as shown in Table 3.
The median progression-free survival (mPFS), as estimated by the Kaplan–Meier method, was 4.5 months (95% CI: 4.0–4.9) in patients receiving gemcitabine and cisplatin, compared to 7.6 months (95% CI: 3.9–11.2) in those treated with the triplet regimen of gemcitabine, cisplatin, and nab-paclitaxel. This difference was statistically significant (p ≤ 0.05). Survival data were censored at 25 months (Table 4; Fig. 3).
Table 4.
Median progression-free survival in both arms.
| Arms | Median PFS (months)/(95% CI) | P-value |
|---|---|---|
| A (doublet therapy) | 4.50 (4.01–4.98) | 0.0001 |
| B (triplet therapy) | 7.60 (3.99–11.20) |
Fig. 3.
Kaplan – Meier Survival Plot for Progression Free Survival.
The median overall survival (mOS), as estimated by the Kaplan–Meier method, was 9.2 months (95% CI: 2.6–15.7) in patients treated with gemcitabine and cisplatin. In contrast, the median OS was not reached in the triplet arm (gemcitabine, cisplatin, and nab-paclitaxel). Survival data were censored at 25 months (Table 5; Fig. 4).
Table 5.
Median overall survival in both arms.
| Arms | Median OS (Months)/(95% CI) |
P-value |
|---|---|---|
| A (doublet therapy) | 9.2 (2.67–15.72) | 0.264 |
| B (triplet therapy) | NR |
Fig. 4.
Kaplan–Meier survival plot for overall survival.
Adverse events were analysed in all patients who received at least one cycle of chemotherapy, including 27 patients in Arm A (doublet) and 27 in Arm B (triplet).
In the doublet arm, the most common adverse events (all grades) were anemia (96.2%), fatigue (77.7%), and neutropenia (48.1%). In the triplet arm, the most frequent adverse events (all grades) were anemia (96.2%), fatigue (96.2%), peripheral neuropathy (96.2%), and neutropenia (77.7%).
The incidence of neutropenia, thrombocytopenia, diarrhoea, fatigue, and peripheral neuropathy (all grades) was significantly higher in the triplet arm compared to the doublet arm (p = 0.024, p = 0.01, p = 0.001, p = 0.04, and p = 0.001, respectively).
For grade 3 toxicities, the most common in Arm A was anemia (14.8%), followed by neutropenia (11.1%) and febrile neutropenia (7.4%). In Arm B, the most frequent grade 3 toxicity was neutropenia (29.6%), followed by febrile neutropenia (14.8%) and anemia (7.4%). However, these differences in grade 3 events between the two arms were not statistically significant. No grade 4 adverse events were observed in either treatment arm (Table 6).
Table 6.
Toxicity profile of patients in both arms.
| Adverse event | All grades (N;%) | Grade 3 (N;%) | ||||
|---|---|---|---|---|---|---|
| Doublet(N = 27) | Triplet(N = 27) | P value | Doublet(N = 27) | Triplet(N = 27) | P value | |
| Hematologic | ||||||
| Anemia | 26 (96.2%) | 26 (96.2%) | 1 | 4 (14.8%) | 2 (7.4%) | 0.386 |
| Neutropenia | 13 (48.1%) | 21 (77.7%) | 0.024 | 3 (11.1%) | 8 (29.6%) | 0.091 |
| Febrile neutropenia | – | – | 2 (7.4%) | 4 (14.8%) | 0.386 | |
| Thrombocytopenia | 5 (18.5%) | 14 (51.8%) | 0.01 | 0 | 0 | NA |
| Gastrointestinal | ||||||
| Increased ALT | 11 (40.7) | 13 (48.1%) | 0.58 | 0 | 0 | NA |
| Other abnormal liver functions | 12 (44.4%) | 15 (55.5%) | 0.414 | 0 | 0 | NA |
| Vomiting | 2 (7.4%) | 2 (7.4%) | 1 | 0 | 0 | NA |
| Nausea | 4 (14.8%) | 2 (7.4%) | 0.386 | 0 | 0 | NA |
| Constipation | 4 (14.8%) | 1 (3.7%) | 0.159 | 0 | 0 | NA |
| Diarrhoea | 3 (11.1%) | 16 (59.2%) | < 0.001 | 0 | 1 (3.7%) | 0.98 |
| General | ||||||
| Hypokalemia | 2 (7.4%) | 2 (7.4%) | 1 | 0 | 0 | NA |
| Hyponatremia | 2 (7.4%) | 2 (7.4%) | 1 | 0 | 0 | NA |
| Maculopapular rash | 2 (7.4%) | 4 (14.8%) | 0.386 | 0 | 0 | NA |
| Anorexia | 12 (44.4%) | 8 (29.6%) | 0.26 | 0 | 0 | NA |
| Fatigue | 21 (77.7%) | 26 (96.2%) | 0.043 | 0 | 0 | NA |
| Impaired KFT | 2 (7.4%) | 2 (7.4%) | 1 | 0 | 0 | NA |
| Infection without neutropenia | 5 (18.5%) | 6 (22.2%) | 0.735 | 0 | 0 | NA |
| Infection with neutropenia | 0 | 1 (3.7%) | 0.97 | 0 | 0 | NA |
| Infection with biliary sepsis | 0 | 0 | NA | 0 | 1 (3.7%) | 0.98 |
| Infection of any type | 4 (14.8%) | 3 (11.1%) | 0.68 | 0 | 0 | NA |
| DVT | 2 (7.4%) | 1 (3.7%) | 0.9 | 0 | 0 | NA |
| Thromboembolic event | 0 | 0 | NA | 1 (3.7%) | 1 (3.7%) | 1 |
| Peripheral neuropathy | 1 (3.7%) | 26 (96.2%) | < 0.001 | 0 | 1 (3.7%) | 0.98 |
| Other | 4 (14.8%) | 5 (18.5%) | 0.715 | 0 | 0 | NA |
Discussion and conclusion
Our findings suggest that adding nab paclitaxel to the standard chemotherapy backbone of gemcitabine and cisplatin may be a promising option for patients with GBC. After a median follow-up of 13.2 months, the ORR was 61.9%, in triplet arm, significantly higher than 13.3% in the doublet arm. Median PFS was also significantly improved in the triplet arm (7.6 months 95% CI, 3.9–11.2) compared to the doublet arm (4.5 months 95% CI, 4.0-4.9). Median OS was not reached during the study period.
Several earlier studies have established gemcitabine–cisplatin as the standard of care in unresectable or metastatic biliary tract cancer (BTC), including non-randomized trials by Doval et al.19, Lee et al.20, and Goldstein et al.21, and the phase III ABC-02 trial22. In a phase II study by Shroff et al.14, the triplet regimen of gemcitabine, cisplatin, and nab-paclitaxel was first evaluated in 60 patients with BTC. Their subsequent phase III trial (SWOG 1815)15 assessed PFS and OS in a broader BTC population, primarily intrahepatic cholangiocarcinoma (ICC), with only 16% of patients having GBC. In contrast, our study focused exclusively on unresectable or metastatic GBC.
Our findings align with Shroff et al.14, who demonstrated clinical activity of the triplet regimen. Compared to the ABC-02 trial22, which reported a higher ORR (81.4%) in the doublet arm, our study’s lower response rates may be attributed to differences in patient population, tumor biology, or sample size. Nonetheless, the ORR in our doublet arm was higher than those reported in single-arm trials by Doval et al.19, Lee et al.20, and Goldstein et al.21. Cross-trial comparisons, however, should be interpreted with caution.
In SWOG 1815 trial15, there was similar significant improvement (p - value = 0.01) in PFS in patients with GBC as compared to patients having ICC or ECC, though this was a subset analysis. Compared to studies like ABC-0223 and Shroff et al.14, our study observed a lower median PFS, possibly due to differences in patient population, genetics, or the small sample size.
Dose reductions were necessary for 22.2% of patients on doublet therapy and 51.8% on the triplet regimen due to toxicity. In the Shroff et al.14 trial, 46% of patients received a modified dose of the triplet therapy due to adverse chemotherapy effects.
One crucial aspect of any chemotherapy regimen is its toxicity profile. Though there was no increase in grade 3 adverse events with the addition of nab-paclitaxel, there were no grade 4 events observed in either of the two arms of the study group. The findings in the triplet arm of our study were similar to the results by Shroff et al.14 where neutropenia was the most common AE at grade 3 or higher, occurring in 19 of the 57 patients (33%).
A direct comparison cannot be made to the SWOG 1815 trial15, regarding the dose modifications and the adverse events, as the relevant subset analysis for only the GBC patient pool is not available.
Beyond chemotherapy, recent advances include immunotherapy. The TOPAZ-1 trial12 evaluated durvalumab with gemcitabine and cisplatin, including 171 patients with GBC. Median PFS was 7.2 months versus 5.7 months for durvalumab and placebo, respectively. OS benefit was observed across all BTC subtypes, though full subgroup analysis is awaited. Similarly, the KEYNOTE-966 trial13 showed that pembrolizumab combined with gemcitabine and cisplatin improved OS to 12.7 months, with no new safety concerns. These trials suggest immunotherapy may offer benefit, but it comes with a financial burden.
Despite their efficacy, immune checkpoint inhibitors remain financially inaccessible to many patients in low- and middle-income countries. In such settings, triplet chemotherapy may offer a more practical and effective alternative. Our findings suggest that this regimen not only improves response rates but could also be explored in neoadjuvant settings for patients with borderline resectable or locally advanced disease.
Our study has several limitations. First, although the sample size met statistical requirements, it remains small, partly due to COVID-19-related restrictions. Second, the study’s follow-up duration was limited, and median OS was not reached. Third, our primary endpoint was ORR rather than OS, which is typically considered more robust in clinical trials.
Despite these limitations, our study is the first to compare gemcitabine–cisplatin–nab-paclitaxel versus gemcitabine–cisplatin exclusively in GBC. Previous trials grouped GBC with other BTC subtypes, despite potential biological differences. Given that North India has one of the highest global incidences of gallbladder cancer, our findings may be particularly relevant to this population and could also offer insights for regions facing similar disease patterns worldwide.
In conclusion, our study provides early evidence supporting the feasibility and efficacy of the triplet chemotherapy regimen in unresectable or metastatic GBC. Further validation through larger, multicentric studies is necessary to determine whether this combination could represent a new standard of care.
Recommendation
Gemcitabine, cisplatin, and nab-paclitaxel combination chemotherapy may be considered as an alternative first-line option for patients with locally advanced or metastatic gallbladder cancer, alongside existing standard-of-care regimens, especially in resource-constraint settings.
Supplementary Information
Below is the link to the electronic supplementary material.
Author contributions
C.K. collected the data and analyzed the data and wrote the manuscript, P.K. planned the study and helped in data collection, R.R. and J.P. helped in the data collection. All authors reviewed the manuscript.
Data availability
The datasets generated and/or during the current study are not publicly available to protect the privacy of the study population. Still, they are available from the corresponding author on reasonable request.
Declarations
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets generated and/or during the current study are not publicly available to protect the privacy of the study population. Still, they are available from the corresponding author on reasonable request.