The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.
To define patterns of recurrence after adjuvant chemotherapy and the ...association with survival.
Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.
Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.
Overall survival, recurrence, and sites of recurrence.
Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P = .03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P = .04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P = .27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P = .85 and P = .35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .03).
There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.
ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434.
HER2 is overexpressed or amplified in a subset of biliary tract cancer. Zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, exhibited tolerability and preliminary anti-tumour ...activity in HER2-expressing or HER2 (also known as ERBB2)-amplified treatment-refractory biliary tract cancer.
HERIZON-BTC-01 is a global, multicentre, single-arm, phase 2b trial of zanidatamab in patients with HER2-amplified, unresectable, locally advanced, or metastatic biliary tract cancer with disease progression on previous gemcitabine-based therapy, recruited at 32 clinical trial sites in nine countries in North America, South America, Asia, and Europe. Eligible patients were aged 18 years or older with HER2-amplified biliary tract cancer confirmed by in-situ hybridisation per central testing, at least one measurable target lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were assigned into cohorts based on HER2 immunohistochemistry (IHC) score: cohort 1 (IHC 2+ or 3+; HER2-positive) and cohort 2 (IHC 0 or 1+). Patients received zanidatamab 20 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate in cohort 1 as assessed by independent central review. Anti-tumour activity and safety were assessed in all participants who received any dose of zanidatamab. This trial is registered with ClinicalTrials.gov, NCT04466891, is ongoing, and is closed to recruitment.
Between Sept 15, 2020, and March 16, 2022, 87 patients were enrolled in HERIZON-BTC-01: 80 in cohort 1 (45 56% were female and 35 44% were male; 52 65% were Asian; median age was 64 years IQR 58–70) and seven in cohort 2 (five 71% were male and two 29% were female; five 71% were Asian; median age was 62 years IQR 58–77). At the time of the data cutoff (Oct 10, 2022), 18 (21%) patients (17 in cohort 1 and one in cohort 2) were continuing to receive zanidatamab; 69 (79%) discontinued treatment (radiographic progression in 64 74% patients). The median duration of follow-up was 12·4 months (IQR 9·4–17·2). Confirmed objective responses by independent central review were observed in 33 patients in cohort 1 (41·3% 95% CI 30·4–52·8). 16 (18%) patients had grade 3 treatment-related adverse events; the most common were diarrhoea (four 5% patients) and decreased ejection fraction (three 3% patients). There were no grade 4 treatment-related adverse events and no treatment-related deaths.
Zanidatamab demonstrated meaningful clinical benefit with a manageable safety profile in patients with treatment-refractory, HER2-positive biliary tract cancer. These results support the potential of zanidatamab as a future treatment option in HER2-positive biliary tract cancer.
Zymeworks, Jazz, and BeiGene.
Goblet cell carcinoid tumours are often considered a subset of appendiceal neuroendocrine tumours which behave more aggressively. They usually metastasize through transcoelomic/peritoneal invasion ...and common sites include the ovaries, peritoneum, and liver. Metastases may have goblet cell carcinoid, signet ring cell carcinoma or classic carcinoid histology. We report the first case in the literature of a patient with a goblet cell carcinoid with lung metastasis, which was associated with unfavourable outcome.
Tiffany Foo and colleagues, Giovanni Brandi and colleagues, and Raja Pramanik and colleagues suggested other stratification factors such as progression-free survival after first-line chemotherapy of ...at least 6 months, previous resection, pretreatment serum CA19.9, peritoneal carcinomatosis, primary tumour site, and molecular profiling results. Platinum sensitivity has never been defined for biliary tract cancer; rather than using an arbitrary cutoff of 6 months, we tailored our definition to this cancer—namely, progression more than 90 days after day 1 of the last cycle of first-line cisplatin and gemcitabine, derived from 9 months' progression-free survival with cisplatin–gemcitabine minus 6 months of chemotherapy.2 Use of tumour markers as stratification factors in advanced disease has the difficulty of selecting a priori a clinically meaningful cutoff for high versus low categories. ...we advise against directly extrapolating the (modest) benefit identified from FOLFOX to other chemotherapy strategies, as suggested by Pramanik and colleagues; adequately designed and powered trials are necessary to test other regimens.
We report a rare presentation of metastatic renal cell carcinoma (RCC) in a 71-year-old man who presented with persistent shoulder pain. MRI revealed widespread lytic lesions within the bones ...suggestive of metastatic disease but extensive imaging including CT chest, abdomen and pelvis with contrast and fluorodeoxyglucose-positron emission tomography did not identify a primary cancer. The diagnosis was ultimately made from a targeted bone and subsequently targeted liver biopsy, whereby immunohistochemistry was consistent with metastatic RCC (mRCC). While bone metastases in RCC are very common, it is extremely rare for patients to present with mRCC and no identifiable renal primary.
Chemotherapy (CT) is widely used for neuroendocrine tumours (NETs), but there are no validated biomarkers to predict response. The Ki-67 proliferation index has been proposed as a means of selecting ...patients for CT, but robust data are lacking. The aim of this study was to investigate the relationship between response to chemotherapy and Ki-67 in NET. We reviewed data from 222 NET patients treated with CT. Tumours were graded according to Ki-67 index: G1 ≤2%, G2 3-20% and G3 >20%. Response was assessed according to RECIST and survival calculated from start of chemotherapy to death. To explore Ki-67 as a marker of response, we calculated the likelihood ratio and performed receiver operating characteristic analysis. Overall, 193 patients had a documented Ki-67 index, of which 173 were also evaluable for radiological response: 10% were G1, 46% G2 and 43% G3; 46% were pancreatic NET (PNET). Median overall survival was 22.1 months. Overall response rate was 30% (39% in PNET vs 22% in non-PNET) and 43% of patients had stable disease. Response rate increased with grade: 6% in G1 tumours, 24% in G2 and 43% in G3. However, maximum likelihood ratio was 2.3 at Ki-67=35%, and the area under the ROC curve was 0.60. As reported previously, a high Ki-67 was an adverse prognostic factor for overall survival. In conclusion, response to CT increases with Ki-67 index, but Ki-67 alone is an unreliable means to select patients for CT. Improved methods to stratify patients for systemic therapy are required.
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