Influence of imatinib as adjuvant therapy on relapse-free survival in patients with gastrointestinal stromal tumors at moderate to high risk of recurrence

119 Background: For patients with KIT+ gastrointestinal stromal tumors (GIST), several algorithms can evaluate the risk of recurrence and initiation of adjuvant therapy following primary GIST resection. With a variety of risk assessment tools and no standardized approach for assessing risk, it is unclear how physicians estimate the risk of recurrence in real-world clinical practice, and how they use the level of risk when considering adjuvant therapy. Methods: We conducted a cross-sectional survey of US oncologists on August 2013. From an existing panel of US physicians, oncologists were randomly asked to participate in an online survey of their assessment and management of GIST recurrence risk after resection of primary resectable disease. Oncologists’ feedback included rated responses by Likert scale and ranked responses by priority. Results: Of 109 participating oncologists, 69 (63%) were in private practice and 61 (56%) were in practice for >10 years. Mitotic count and primary tumor size were the most influential factors chosen for assessing risk of recurrence, followed by presence of tumor rupture during surgery, tumor location, and presence of genetic mutations. A majority of oncologists (56%) reported the revised NIH criteria as the preferred risk classification tool, mainly because it was easy to use and remember. Initial level of risk assessed after GIST resection was the key factor influencing initiation, dosage, and duration of adjuvant therapy with imatinib. 98% of physicians would treat high risk patients with adjuvant imatinib, whereas 79% would consider adjuvant treatment for intermediate risk patients, and 28% for low risk patients. The percentage who would prescribe at least 3 years of adjuvant therapy varied from 26% for low-risk patients to 52% for intermediate-risk patients and 76% for high-risk patients. Conclusions: Level of risk of recurrence is a key factor when considering adjuvant therapy after resection of resectable GIST. However, significant variability exists in the perception physicians have regarding the initiation of adjuvant therapy among intermediate to high risk patients. This may be attributed to the variability in the different risk assessment tools and criteria.

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The real world outcomes of 3-year adjuvant therapy with imatinib in patients with high-risk molecular profiled gastrointestinal stromal tumors (GIST).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e23524 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e23524-e23524

Author(s):

Piotr Rutkowski ◽

Marcin Zietek ◽

Bozena Cybulska-Stopa ◽

Joanna Streb ◽

Stanislaw Gluszek ◽

...

Keyword(s):

Clinical Trials ◽

High Risk ◽

Adjuvant Therapy ◽

Real World ◽

Gastrointestinal Stromal Tumors ◽

Disease Relapse ◽

Adjuvant Imatinib ◽

Stromal Tumors ◽

Exon 9 ◽

Exon 11

e23524 Background: The real-world data on outcomes of adjuvant therapy in high-risk gastrointestinal stromal tumors (GIST) are very limited. Methods: We have analyzed the data of 107 consecutive patients (52 male, 56 female) with GIST after resection treated with adjuvant imatinib (for planned 3 years with initial dose 400 mg daily, started not later than 4 months after operation) in 6 oncological centers in 2013-2018. All patients were required to have high risk of recurrence (at least 50% according to NCCN/AFIP criteria), known mutational status to exclude PDGFRA D842V mutants and KIT/PDGFRA-wild type cases from therapy. Median follow-up time was 24 months. Results: The most common primary localization of GIST was small bowel (63 patients; 59%), followed by the stomach (40 patients; 37%). The majority of GIST cases harbored exon 11 KIT mutations (88 cases, 82%), 11 cases had exon 9 KIT mutations (10%), 8 had other KIT/PDGFRA mutations potentially sensitive to imatinib. Thirty three patients (31%) finished 3-year adjuvant imatinib therapy as planned, 59 (55%) still continue therapy, 4 (4%) patients had finished adjuvant therapy prematurely due to toxicity, 6 (6%) due to disease progression on treatment and 5 (4%) due to other reasons. The disease relapse was detected in 16 patients, of them in 4 cases in exon 9 KIT mutants (36%), and 10 cases in patients with exon 11 KIT mutations (11%) [p < 0.05]. Estimated 4-year relapse-free survival (RFS) rate is 78%. Conclusions: The early results of adjuvant therapy with imatinib in routine practice outside clinical trials in high-risk mutation-drive GIST patients only confirm high efficacy of this therapy with better tolerability than in clinical trials. Moreover, overrepresentation of exon 9 KIT mutants in a group of patients with disease relapse may indicate that standard 400 mg dose in adjuvant treatment is not sufficient for prevention of disease relapse.

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Phase II study of pembrolizumab after chemoradiotherapy (CRT) as adjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients at high risk of recurrence following preoperative CRT plus surgery.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.tps259 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. TPS259-TPS259

Author(s):

Chih-Hung Hsu ◽

Jhe-Cyuan Guo ◽

Ta-Chen Huang ◽

Hung-Yang Kuo ◽

Chia-Chi Lin ◽

...

Keyword(s):

Clinical Trial ◽

Squamous Cell Carcinoma ◽

High Risk ◽

Adjuvant Therapy ◽

Cell Carcinoma ◽

Phase Ii ◽

Squamous Cell ◽

Phase Ii Study ◽

Free Survival ◽

Risk Of Recurrence

TPS259 Background: LA-ESCC is a potentially curable disease, for which preoperative CRT followed by esophagectomy is a standard-of-care. Previous studies have identified that close/involved margin and lymph node metastasis with extranodal invasion (ENI) in post-CRT surgical specimens are associated with increased risk of recurrence. In CheckMate-577 trial, adjuvant nivolumab significantly improved disease-free survival (DFS) in patients with esophageal cancer treated with preoperative CRT and surgery; in another trial (the “PACIFIC” trial), adjuvant durvalumab has significantly improved overall survival (OS) in stage III non-small cell lung cancer treated with definitive CRT. We hypothesize that adding pembrolizumab to CRT as an adjuvant therapy would improve the outcomes of LA-ESCC patients who are treated with preoperative CRT plus esophagectomy and with high-risk of recurrence. Methods: This single institution single-arm phase II study include patients with histologically confirmed LA-ESCC (AJCC 7th staging system:cT3-4aN0M0 or T1-4aN1-3M0) harboring at least one risk factor (closed/involved margin, ENI, or ypN2-3) in post-CRT surgical specimens. Patients with adenocarcinoma of esophagus or gastroesophageal junction or synchronously diagnosed with a squamous cell carcinoma of aero-digestive way other than ESCC are excluded. Patients enrolled will receive adjuvant weekly cisplatin–CRT (cisplatin, 30mg/m2 for 2 cycles every week; radiotherapy, 180-200 cGy/fraction for 10-13 times) followed by pembrolizumab (200 mg, every 3 weeks, for 18 cycles). The primary endpoint of this study is 1-year relapse-free survival (RFS) rate; and the key secondary endpoints include RFS, 3-year RFS rate, OS, 3-yr OS rate, toxicity and safety. The study, registered with clinical trial ID of NCT03322267, started patient enrollment in Aug 2018. As of Aug of 2020, 11 of 46 planned patients have been enrolled. Clinical trial information: NCT03322267.

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Does Gastrointestinal Bleeding Affect the Prognosis of Patients With Gastrointestinal Stromal Tumor: A Meta-analysis.

10.21203/rs.3.rs-634354/v1 ◽

2021 ◽

Author(s):

Yue Zhang ◽

Qi Liu ◽

Hao Xu

Keyword(s):

Overall Survival ◽

Gastrointestinal Bleeding ◽

Gastrointestinal Stromal Tumor ◽

Random Effects ◽

Gastrointestinal Stromal Tumors ◽

Meta Analysis ◽

Random Effects Model ◽

Relapse Free Survival ◽

Free Survival ◽

Stromal Tumors

Abstract Background: The effect of gastrointestinal bleeding on the prognosis of gastrointestinal stromal tumors has been widely studied in recent years, but it is still controversial. Therefore, we performed the first comprehensive meta-analysis to evaluate the effect of gastrointestinal bleeding on the prognosis of gastrointestinal stromal tumors.Methods: We searched PubMed, MEDLINE, Web of Science, EMBASE, and Cochrane Library databases to recruit studies on the effect of gastrointestinal bleeding on the prognosis of patients with gastrointestinal stromal tumor. Eight studies containing 2915 patients were involved in this meta-analysis until May 31, 2021. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to estimate the effect using random-effects model. Results: The pooled results revealed that gastrointestinal bleeding was not associated with relapse-free survival (HR = 1.33, 95% CI 0.66-2.68, P < 0.001; random-effects model I2=87.7, P < 0.001) and overall survival (HR = 1.29, 95% CI 0.43-3.87, P < 0.001; random-effects model I2=88.9, P < 0.001) in patients with gastrointestinal stromal tumors. Conclusions: Our present a meta-analysis indicates that gastrointestinal bleeding has no effect on relapse-free survival and overall survival of patients with gastrointestinal stromal tumors, although gastrointestinal bleeding is one of the major clinical symptoms of gastrointestinal stromal tumors.

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LONG-TERM RESULTS OF TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN PATIENTS WITH A HIGH RISK OF RECURRENCE

International Journal of Applied and Fundamental Research (Международный журнал прикладных и фундаментальных исследований) ◽

10.17513/mjpfi.13188 ◽

2021 ◽

pp. 35-39

Author(s):

K.E. Kiseleva ◽

E.A. Kiselev

Keyword(s):

High Risk ◽

Gastrointestinal Stromal Tumors ◽

Long Term Results ◽

Risk Of Recurrence ◽

Stromal Tumors ◽

Results Of Treatment

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Laparoscopy-Assisted versus Open Surgery for Gastrointestinal Stromal Tumors of Jejunum and Ileum: Perioperative Outcomes and Long-Term Follow-Up Experience

The American Surgeon ◽

10.1177/000313481207801235 ◽

2012 ◽

Vol 78 (12) ◽

pp. 1399-1404 ◽

Cited By ~ 3

Author(s):

Ping Wan ◽

Chen Li ◽

Min Yan ◽

Chao Yan ◽

Zheng Gang Zhu

Keyword(s):

Gastrointestinal Stromal Tumors ◽

Open Surgery ◽

Postoperative Outcomes ◽

Open Group ◽

Perioperative Outcomes ◽

Relapse Free Survival ◽

Free Survival ◽

Stromal Tumors ◽

Significant Difference

Whether laparoscopy-assisted resections for gastrointestinal stromal tumors (GISTs) of small bowel can achieve more benefits on the aspect of postoperative outcomes than open surgery remains a question. The aim of this study is to evaluate the benefits of laparoscopy-assisted surgery for GISTs of jejunum and ileum on the perioperative outcomes and long-term relapse-free survival. From January 2004 to December 2010, 81 patients who underwent either laparoscopy-assisted (LAP group, n = 43) or open surgery (OPEN group, n = 38) were included in final analysis after the eligibility criteria. Clinicopathological characteristics of the selected patients were similar between the two groups. Oral intake was significant earlier ( P < 0.001) and postoperative hospital stay duration was significantly shorter ( P < 0.001) in the LAP group than in the OPEN group. The complication rate of patients in the LAP group and OPEN group was 9.3 and 26.3 per cent, respectively ( P = 0.04). No significant difference was observed in terms of 5-year relapse-free survival between LAP and OPEN groups (91.1 vs 93.8%, P = 0.4). Laparoscopy-assisted surgery for GISTs of jejunum and ileum could get preferable short-term postoperative outcomes and similar long-term relapse-free survival compared with open surgery, so it should be recommended for GISTs of the small intestine.

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A phase III study of atezolizumab (atezo) vs placebo as adjuvant therapy in renal cell carcinoma (RCC) patients (pts) at high risk of recurrence following resection (IMmotion010).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.tps4598 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. TPS4598-TPS4598 ◽

Cited By ~ 7

Author(s):

Robert Uzzo ◽

Axel Bex ◽

Brian I. Rini ◽

Laurence Albiges ◽

Cristina Suarez ◽

...

Keyword(s):

High Risk ◽

Adjuvant Therapy ◽

Distant Metastasis ◽

Single Agent ◽

Tumor Resection ◽

Disease Free Survival ◽

Phase Iii ◽

Disease Stage ◽

Free Survival ◽

Risk Of Recurrence

TPS4598 Background: Nephrectomy is the SOC in early RCC; however, the 5-y relapse rate is 30-40% in stage II or III pts, with tumor stage and grade correlating with survival and recurrence after surgery. Currently, there is a limited role for adjuvant therapy after nephrectomy in pts who have had complete tumor resection; observation is standard. In a Ph II first-line metastatic RCC study, treatment with single-agent atezo (anti–PD-L1) resulted in an ORR of 25%. Thus, IMmotion010, a Ph III, multicenter, randomized, placebo-controlled, double-blinded trial, will evaluate the efficacy and safety of atezo as adjuvant therapy in RCC pts who are at high risk of recurrence after resection (NCT03024996). Methods: Eligible RCC pts (clear cell or sarcomatoid histologies) will have undergone nephrectomy (radical or partial) and be at high risk of recurrence (T2 Grade 4, T3a Grade 3-4, T3b/c any Grade, T4 any Grade or TxN+ any Grade) or have had complete resection of limited metachronous/synchronous metastasis. Pts must show no residual disease or evidence of metastases by CT scan at enrollment. ECOG PS ≤ 1 and tumor specimens evaluable for PD-L1 will also be required. Pts will be randomized 1:1 to receive atezo 1200 mg IV q3w or placebo IV q3w for 16 cycles or 1 y; stratification will be by disease stage (T2/T3a vs T3b/c/T4/N+ vs metastasectomy), region (North America [excluding Mexico] vs rest of world) and PD-L1 status on tumor-infiltrating immune cells (IC; PD-L1 IC expression < 1% vs ≥ 1%). The primary endpoint is independent review facility (IRF)-assessed disease-free survival (DFS), defined as the time from randomization to the first documented recurrence event (local recurrence, new primary RCC, distant metastasis) or death. Secondary endpoints include OS, investigator-assessed DFS, IRF-assessed and investigator-assessed DFS in pts with ≥ 1% PD-L1 IC, disease-specific survival, distant metastasis-free survival and the 3-y rates of IRF-assessed DFS and investigator-assessed DFS. Safety and biomarkers will be evaluated. The planned analysis will occur when at least ≈ 65% of pts in the 2 populations have died. 664 pts will be enrolled at 150-200 sites worldwide. Clinical trial information: NCT03024996.

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