Search

Background Tyrosine kinase inhibitors remain a cornerstone in managing metastatic clear cell renal cell carcinoma (RCC). The 4 weeks on/2 weeks off intermittent sunitinib schedule could result in rebound angiogenesis and tumor progression in the 2-week rest period. We propose using bevacizumab during this period for continuous antiangiogenic effects. Method This was a phase I/II study of patients with advanced clear cell RCC. Sunitinib was given 50 mg daily on a 4-week on/2-week off schedule. Bevacizumab was given on day 29 of each sunitinib cycle. The bevacizumab starting dose was 5 mg/kg, and the dose was escalated to 10 mg if there was no dose-limiting toxicity. The primary endpoints were response rate and progression-free survival (PFS). Results Twenty-five patients were recruited. The study was closed prematurely because of poor accrual. No dose-limiting toxicity was observed with 5 mg bevacizumab. One patient achieved a complete response, and 12 achieved a partial response (52% response rate). At a median follow-up of 42.2 months (95%, confidence interval (CI) 32.9 to 51.4), the median PFS duration was 16.5 months (95% CI 4.1-28.8), and the median overall survival time was 33.3 months (95% CI 19.4-47.3). Twenty-two patients (88%) had at least one grade 3 or 4 toxicity; the most common were thrombocytopenia (32%), lymphopenia (32%), hypertension (28%), and fatigue (24%). Conclusion Continuous angiogenesis blockade by adding bevacizumab to the sunitinib on/off regimen for advanced RCC yields significant antitumor activity with manageable increased toxicity.

Background. Numerous chemotherapeutic agents have antitumor activity in recurrent/metastatic (R/M) nasopharyngeal cancer (NPC). Evidence of capecitabine’s effectiveness as monotherapy is limited. Capecitabine tolerability in solid malignancies has ethnic and geographical variability. We investigated capecitabine’s tolerability and identified potential prognostic factors for clinical outcomes in R/M NPC. Methods. A consecutive retrospective cohort of patients who received capecitabine as the first recurrence, second- or third-line monotherapy for metastatic NPC (2011–2019) was reviewed concerning patient characteristics, pathological features, treatment outcomes, and toxicity. Results. Fifty-one patients were eligible (median age at diagnosis: 42 [35.5–52.5] years). Most patients (78.4%) tolerated a standard oral dose of 1,250 mg/m2 capecitabine (2 weeks on/1 week off) in a 3-week cycle. The objective response rate was 49%, and the disease control rate was 66.7%, with a median response duration of 6.2 months. Hand-foot syndrome (HFS) was associated with a higher objective response rate (odds ratio, 5.1 [95% confidence interval: 1.18–21.98]; P = 0.02 ). The median follow-up duration was 17.8 (interquartile range: 7.8–30.4) months. The median (95% confidence interval) progression-free survival and overall survival were 6.6 (4.3–8.8) and 32.7 (25.9–39.5) months, respectively. HFS ( P = 0.02 ), better performance status ( P = 0.02 ), and absence of brain metastasis ( P = 0.04 ) were associated with prolonged progression-free survival. Conclusion. Capecitabine monotherapy is effective and well-tolerated as a palliative treatment for R/M NPC. Despite the lower incidence of HFS in our patients, it remained a favorable prognostic factor for objective response and progression-free survival.

Background Gastric cancer (GC) carries a poor survival outcome despite the availability of many therapeutic agents active in treatment. In this study, we aimed to evaluate the survival outcomes of metastatic GC treatment from a single center in Saudi Arabia and identify possible prognostic factors. Methodology Data on patients diagnosed with metastatic GC between December 2009 and November 2013 were collected and analyzed. Results During this period, 41 patients were diagnosed with a median age at diagnosis of 52 years, and 56.1% of patients were males. Only four (9.2%) patients had human epidermal growth factor receptor 2 overexpression. Overall, 83% were treated with oxaliplatin-based chemotherapy. The median progression-free survival (PFS) and overall survival (OS) were 4.1 and 15.4 months, respectively. Female sex was an independent prognostic factor for better PFS and OS. Normal lymphocyte count was associated with improved PFS. Conclusions Our study highlights poor outcomes in patients with metastatic GC and the need for further research in this field.

The peritoneum frequently is the only recurrence site after radical resection of gastric cancer. Data suggest that hyperthermic intraperitoneal chemotherapy (HIPEC) and intraoperative radiotherapy (IORT) reduce peritoneal recurrence and possibly improve survival for patients with resected gastric and serosal involvement. This study aimed to evaluate the efficacy of combining prophylactic HIPEC and IORT after radical resection of localized gastric cancer.In this retrospective study, the medical records of adult patients with histologically proven gastric/gastroesophageal adenocarcinoma who underwent radical resection with curative intent were evaluated for recurrence and survival according to whether they received prophylactic HIPEC and IORT.The eligibility criteria were met by 58 patients, 33 of whom underwent prophylactic HIPEC and IORT after radical surgery. Overall, 91% the HIPEC/IORT group and 72% of the surgery-only group had ≤pT3 disease. The median follow-up period was 26.6 months for the HIPEC/IORT group and 50.6 months for the surgery group. Locoregional recurrence occurred for six patients (18.1%) in the HIPEC/IORT group and five patients (20%) in the surgery-only group, with peritoneal metastasis (PM) occurring in respectively three (9%) and six (24%) patients. The median recurrence-free survival (RFS) duration was 23.2 months (95% confidence interval [CI] 6.5-39.9 months) for the HIPEC/IORT group versus 24.8 months (95% CI 0.0-51.1 months) for the surgery-only group (p = 0.88), and the corresponding 5-year overall survival (OS) estimates were 69% and 58%.Prophylactic HIPEC and IORT after radical surgery for localized gastric or gastroesophageal cancer did not improve RFS or OS for an unselected group of patients at risk for peritoneal recurrence.

Background. The outcome of patients with refractory metastatic colorectal cancer (mCRC) treated with trifluridine/tipiracil (FTD/TPI) beyond the second-line has not been studied in Saudi Arabia. Therefore, this multicenter retrospective analysis was conducted to evaluate the efficacy of FTD/TPI. Methods. This multicenter retrospective analysis included five centers in Saudi Arabia. FTD/TPI was administered to all the patients beyond the oxaliplatin- and irinotecan-based chemotherapy regimens. The electronic medical records were reviewed, and progression-free survival (PFS) and overall survival (OS) were determined. Results. The study included 100 patients with a mean age of 55.4 ± 11.8 years. The overall response to FTD/TPI was 4%. The median PFS was 4 months (95% confidence interval (CI) 3.487–4.513), and the median OS was 11 months (95% CI, 9.226–12.771). In a Cox regression analysis of the independent predictors for PFS, advanced stage of the disease ( P = 0.037 ; HR, 2.614; and CI, 1.102–7.524), presence of lymph node metastasis ( P = 0.018 ; HR, 3.664; and 95% CI, 1.187–8.650), and >2 metastatic sites ( P = 0.020 ; HR, 1.723; and 95% CI, 1.089–2.727) were independent factors predicting disease progression. The Cox regression analysis confirmed that age ≥ 55 years ( P = 0.046 ; HR, 1.667; and 95%, 1.097–3.100), advanced disease stage ( P = 0.044 ; HR, 1.283; and 95% CI, 1.035–2.940), prior use of adjuvant chemotherapy ( P = 0.037 ; HR, 0.892; and 95% CI, 0.481–0.994), liver metastasis ( P = 0.025 ; HR, 2.015; and 95% CI, 1.091–3.720), >2 metastatic sites ( P = 0.038 ; HR, 1.248; and 95% CI, 1.036–1.846), development of neutropenia after receiving first cycle of FTD/TPI ( P = 0.042 ; HR, 1.505; and 95% CI, 1.064–2.167), and increased number of FTD/TPI cycles ( P = 0.002 ; HR, 0.769; and 95% CI, 0.664–0.891) were independent variables for OS. Conclusion. Treatment with FTD/TPI is feasible and effective in daily clinical practice in Saudi Arabian patients. The risk of progression increased with advanced disease stage, lymph node metastasis, bone metastasis, and metastasis to >2 sites. Age ≥ 55 years, advanced disease stage, liver metastasis, metastasis to >2 sites, neutropenia after the first cycle of FTD/TPI, and increased number of FTD/TPI cycles were independent factors predicting mortality.

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with hormonal treatment is the standard of care in the management of hormone receptor positive, human epidermal growth factor receptor-2 (Her2) negative metastatic breast cancer (MBC) patients. Data coming from the Middle east region is very rare and our patients’ population were poorly represented in the CDK4/6 inhibitors landmark clinical trials, This retrospective study is to evaluate our real-world experience with this treatment combination in our patients’ population. Patients and methods: A retrospective study was conducted in a middle eastern tertiary institution, where the clinical data of treatment outcome and toxicity were collected from the electronic medical records of 164 patients with hormone receptor positive, Her2 negative MBC who were managed with CDK4/6 inhibitors in combination with hormonal treatment, at and beyond first line of treatment. Progression free survival (PFS) was the study primary objective, Objective response rate (OR), Overall survival (OS), and toxicity profile were the secondary objectives. Results: From January 2017 to April 2021, 164 patients (5 men and 159 women) were managed with CDK4/6 inhibitors in combination with hormonal treatment for MBC, median age was 52 years (IQR: 45-59), 63% of patients were postmenopausal, 60% had luminal type B tumors, 22% had Her2 expression of 2+ by IHC, 55% had de Novo metastases, 67% had visceral metastases, 61% defined to have endocrine resistant disease (13% primary and 48% secondary resistance), CDK inhibitors (46% Palbociclib, 54% Ribociclib) were given as 1st, 2nd and beyond 2nd line in (48%, 28% and 24% respectively), at a median duration of follow up of 25.3 months (IQR: 13.8-33.9 months), the median PFS for the overall group was 14.2 months (CI 09.8-18.7), it was highest for 1st line treatment 19 months vs 15 and 5 months for the 2nd and beyond 2nd line treatment respectively. The median overall survival was 51.6 months (CI 35.8-67.5) for the whole group, 50.3 and 51.6 months for 1st and 2nd line vs 33.1 months for beyond 2nd line treatment. 5% of patients had achieved complete response, 37% partial response, and 24% had stable disease, with a clinical benefit rate of 74%. A body mass index (BMI) < 30, KI67 < 20%, luminal type A, de Novo metastases, Ribociclib as a CDKi, Aromatase inhibitor (AI) as the hormonal partner, and introducing the treatment combination in early treatment lines (1st and 2nd lines) were all associated with significantly higher PFS in univariate analysis. BMI and AI were the only factors associated with significantly higher PFS in multivariate analysis. Efficacy was consistent regardless of the menopausal status, type of endocrine resistance, and site of metastases. The most common toxicities were neutropenia, fatigue, vomiting, diarrhea, QTC prolongation and hepatic toxicity, the most common G3&4 toxicity were Neutropenia 56%, hepatic toxicity 5.4% and QTC prolongation in 4.3%. Treatment was permanently stopped because of toxicity in 12 patients (7.3%). Conclusion: Our real-life data came consistent with the pivotal clinical trials’ results, encouraging and supporting the use of CDK 4/6 inhibitors in combination with hormonal treatment in our patient population with metastatic breast cancer, especially in the early treatment lines, deferring the start of more toxic therapies to a later stage. Citation Format: Ahmed Mostafa Gad, Adhar AlSayed, Aisha AlShibani, Taher Twegieri, Kausar Suleman, Dahish Ajarim. Clinical outcome and toxicity profile of Cyclin-dependent kinase 4/6 inhibitors in combination with hormonal treatment in management of metastatic breast cancer patients: A Middle-East Real World Experience. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-41.

665 Background: Tyrosine kinase inhibitors remain a corner stone in the management of metastatic clear cell renal cell carcinoma (RCC). The intermittent schedule of sunitinib with 4 weeks on/2 weeks off could result in a rebound angiogenesis and tumor progression in the 2 weeks rest period. We propose the use of bevacizumab to alternate with sunitinib to attain continuous anti-angiogenesis during sunitinib therapy. Methods: This was a phase I/II design. Patients advanced clear cell RCC were recruited. Sunitinib was given as 50 mg daily on 4 weeks on/2 weeks off schedule. Bevacizumab was given on day 29 of each sunitinib cycle. Bevacizumab starting dose was 5 mg/kg and the dose was escalated to 10 mg if no dose limiting toxicity. Primary endpoints were response rate and progression-free survival. Results: Twenty-five patients were recruited. The study was closed prematurely because of poor accrual. No dose limiting toxicity was found on the 5 mg dose level of bevacizumab. One patient achieved complete response and 12 achieved partial response for a response rate of 52%. At a median follow up was 42.2 months (95%, confidence interval (CI) 32.9 to 51.4), the median progression-free survival was 16.5 months (95% CI 4.1-28.8), and the median overall survival was 33.3 months (95% CI 19.4-47.3). Twenty-two patients (88%) had at least one grade 3 or 4 toxicity. The commonest grade 3 or 4 toxicity was thrombocytopenia and lymphopenia each occurring at a rate of 32%, followed by hypertension at a rate of 28% followed by fatigue at a rate of 24%. Conclusions: Continuous angiogenesis blockade by adding bevacizumab to sunitinib 4 weeks on and 2 weeks break regimen in advanced RCC produce significant anti-tumor activity with manageable increased toxicity. Clinical trial information: NCT02919371 .

94 Background: The achievement of a pathological complete response with preoperative concurrent chemoradiotherapy in locally advanced rectal cancer has been found to correlate with a reduced incidence of local and distant recurrences. With the radiosensetizing properties of gemcitabine, we tested the efficacy and toxicity of preoperative concurrent infusional gemcitabine and radiotherapy in locally advanced rectal cancer. Methods: This was a phase II, single-arm, single-institution trial. Eligibility included a diagnosis of rectal adenocarcinoma with stage T2–4 and/or nodal involvement by MRI and endoscopic rectal ultrasound, age ≥ 18 years and no prior chemotherapy or radiotherapy. Patients received preoperative radiation at a dose of 50.4–54 Gy over 28 days with concurrent infusional gemcitabine administered at a dose of 100 mg/m2 over the course of 24 hours weekly for 6 weeks. The primary endpoint was a pathological complete response (pCR). The trial was registered at clinicaltrials.gov (NCT02919878). Results: Forty patients were enrolled in the study. All of the patients completed the planned therapy, except for one patient who died at the end of his concurrent chemoradiation. Eight patients did not undergo surgery, with 1 patient dying (mentioned above), 2 patients progressing to nonresectable disease and 5 patients withdrawing consent. Six patients progressed prior to or had metastases identified at surgery, with 2 patients having unresectable metastases, 3 patients having resectable liver metastases and 1 patient having a peritoneal metastasis (not resected). Serious adverse events were reported in 8 patients (20%). The most common grade 3–4 toxicities in the preoperative period included lymphopenia (50%), neutropenia (41%), anemia (15%), diarrhea (12%), abdominal pain (12%) and proctitis (8%). Out of the 32 patients who underwent surgery, 7 patients achieved pCR at a rate of 20%. With a median follow-up of 30 months, 4 additional patients relapsed (all of these patients had distant metastases, with one subsequently having a local recurrence). The 3-year event-free and overall survival rates were 70% and 85%, respectively. Conclusions: Concurrent preoperative chemoradiotherapy using infusional gemcitabine for locally advanced rectal cancer achieved an encouraging local control. Distant metastasis remains not decreased. Further investigations of a preoperative regimen containing gemcitabine is warranted. Clinical trial information: NCT02919878.