Median Number Of Chemotherapy Cycles Research Articles

J-AVENUE: A retrospective, real-world study evaluating patient characteristics and outcomes in patients with advanced urothelial carcinoma treated with avelumab first-line maintenance therapy in Japan.

The JAVELIN Bladder 100 phase 3 trial showed that avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with advanced urothelial carcinoma who were progression-free following first-line platinum-based chemotherapy. We report findings from J-AVENUE (NCT05431777), a real-world study of avelumab first-line maintenance therapy in Japan. Medical charts of patients with advanced urothelial carcinoma without disease progression following first-line platinum-based chemotherapy, who received avelumab maintenance between February and November 2021, were reviewed. Patients were followed until June 2022. The primary endpoint was patient characteristics; secondary endpoints included time to treatment failure and progression-free survival. In 79 patients analyzed, median age was 72 years (range, 44-86). Primary tumor site was upper tract in 45.6% and bladder in 54.4%. The most common first-line chemotherapy regimen was cisplatin + gemcitabine (63.3%). Median number of chemotherapy cycles received was four. Best response to chemotherapy was complete response in 10.1%, partial response in 58.2%, and stable disease in 31.6%. Median treatment-free interval before avelumab was 4.9 weeks. With avelumab first-line maintenance therapy, the disease control rate was 58.2%, median time to treatment failure was 4.6 months (95% CI, 3.3-6.4), and median progression-free survival was 6.1 months (95% CI, 3.6-9.7). Findings from J-AVENUE show the effectiveness of avelumab first-line maintenance in patients with advanced urothelial carcinoma in Japan in clinical practice, with similar progression-free survival to JAVELIN Bladder 100 and previous real-world studies, supporting its use as a standard of care.

Adapted EXTREME regimen in the first-line treatment of fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (ELAN-FIT): a multicentre, single-arm, phase 2 trial

A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME trial, few older patients were included. We aimed to evaluate the efficacy and tolerance of an adapted EXTREME regimen in fit, older patients with recurrent or metastatic HNSCC. This single-arm, phase 2 study was done at 22 centres in France. Eligible patients were aged 70 years or older and assessed as not frail (fit) using the ELAN Geriatric Evaluation (EGE) and had recurrent or metastatic HNSCC in the first-line setting that was not eligible for local therapy (surgery or radiotherapy), and an Eastern Cooperative Oncology Group performance status of 0-1. The adapted EXTREME regimen consisted of six cycles of fluorouracil 4000 mg/m2 on days 1-4, carboplatin with an area under the curve of 5 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m2 on cycle 1-day 1, and 250 mg/m2 subsequently), all intravenously, with cycles starting every 21 days. In patients with disease control after two to six cycles, cetuximab 500 mg/m2 was continued once every 2 weeks as maintenance therapy until disease progression or unacceptable toxicity. Granulocyte colony-stimulating factor was systematically administered and erythropoietin was recommended during chemotherapy. The study was based on the two-stage Bryant and Day design, combining efficacy and toxicity endpoints. The primary efficacy endpoint was objective response rate at week 12 after the start of treatment, assessed by central review (with an unacceptable rate of ≤15%). The primary toxicity endpoint was morbidity, defined as grade 4-5 adverse events, or cutaneous rash (grade ≥3) that required cetuximab to be discontinued, during the chemotherapy phase, or a decrease in functional autonomy (Activities of Daily Living score decrease ≥2 points from baseline) at 1 month after the end of chemotherapy (with an unacceptable morbidity rate of >40%). Analysis of the coprimary endpoints, and of safety in the chemotherapy phase, was based on the per-protocol population, defined as eligible patients who received at least one cycle of the adapted EXTREME regimen. Safety in the maintenance phase was assessed in all patients who received at least one dose of cetuximab as maintenance therapy. The study is registered with ClinicalTrials.gov, NCT01864772, and is completed. Between Sept 27, 2013, and June 20, 2018, 85 patients were enrolled, of whom 78 were in the per-protocol population. 66 (85%) patients were male and 12 (15%) were female, and the median age was 75 years (IQR 72-79). The median number of chemotherapy cycles received was five (IQR 3-6). Objective response at week 12 was observed in 31 patients (40% [95% CI 30-51]) and morbidity events were observed in 24 patients (31% [22-42]). No fatal adverse events occurred. Four patients presented with a decrease in functional autonomy 1 month after the end of chemotherapy versus baseline. During chemotherapy, the most common grade 3-4 adverse events were haematological events (leukopenia [22 patients; 28%], neutropenia [20; 26%], thrombocytopenia [15; 19%], and anaemia [12; 15%]), oral mucositis (14; 18%), fatigue (11; 14%), rash acneiform (ten; 13%), and hypomagnesaemia (nine; 12%). Among 44 patients who received cetuximab during the maintenance phase, the most common grade 3-4 adverse events were hypomagnesaemia (six patients; 14%) and acneiform rash (six; 14%). The study met its primary objectives on objective response and morbidity, and showed overall survival to be as good as in younger patients treated with standard regimens, indicating that the adapted EXTREME regimen could be used in older patients with recurrent or metastatic HNSCC who are deemed fit with use of a geriatric evaluation tool adapted to patients with head and neck cancer, such as the EGE. French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer), Sandoz, GEFLUC, and GEMLUC. For the French translation of the abstract see Supplementary Materials section.

Neoadjuvant Chemotherapy in Locally Advanced Sinonasal Teratocarcinosarcoma a Rare Malignancy: An Audit From an Academic Tertiary Care Centre in India

AimsSinonasal teratocarcinosarcomas (SNTCS) are rare sinonasal malignancies, the incidence of which is less than 1% of all tumors. There is limited data available on SNTCS's, often as case reports and small case series. The management of SNTCS is complicated because of its location, locally aggressive biology, difficulty in achieving complete resection, and limited data on chemotherapy in these malignancies. This audit was performed to understand the role of neoadjuvant chemotherapy (NACT) in SNTCS's, its ability to downstage the disease, achieve complete resection, and impact on long-term survival outcomes. MethodsThis was a retrospective analysis of a prospectively maintained database approved by the Institutional Ethics Committee (IEC). The baseline characteristics, the extent of tumor, Kadish stage, NACT regimen, and adverse events were extracted from the Electronic Medical Records and the patient's case file. Patients with baseline extensive/inoperable disease were referred for NACT from the multidisciplinary joint clinic followed by response assessment (RECIST v1.1). Patients underwent skull-base surgery if respectable post-completion of NACT, however, if deemed unresectable were treated with non-surgical modalities or palliative therapies. ResultsThe data of 27 patients were evaluated from the year 2015–2022. The median age was 42 years (IQR:30–56) and 85.2% (n = 23) were males. The ECOG-PS was 0–1 in 88.8% (n = 24) patients. All 27 patients received NACT in view of extensive disease at presentation. 74.1% (n = 20) patients received Cisplatin-Etoposide and 25.9% (n = 7) received other chemotherapy regimens. The median number of chemotherapy cycles was 2(IQR:2–3). 96.3% patients (n = 26) completed the planned NACT cycles. 70.4% (n = 19) patients achieved a partial response in post-NACT imaging. 77.8% (n = 18) underwent surgery, 18.5% (n = 5) received CTRT, and 7.4% (n = 2) received definitive-RT alone. The median PFS and OS of the cohort was 19months (95%CI:12.0–25.6) and 23months (95%CI:5.94–40.06) respectively. ConclusionNACT is safe, feasible, and effective with significant response rates, leading to effective downstaging, resectability and improved survival in patients with locally advanced SNTCS's.

Association of intensifying supportive care with improved survival in patients with gastric cancer with malignant ascites.

294 Background: Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that precludes receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan. Methods: We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010-2022. We compared survival between patients diagnosed from 2010-2018, which will be referred to as the historical control era and patients diagnosed from 2019-2022, which will be called the aggressive supportive care era. Results: 54 patients were included in our analysis; 31 patients were treated in the historical control time frame and 23 patients treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p=0.008). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p=0.001). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median overall survival for historical control patients was 5.4 months as compared to 10.4 months for patients treated during aggressive supportive care era (p=0.035). Conclusions: Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared to historic controls.Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.

Intensifying supportive care is associated with improved survival in gastric cancer patients with malignant ascites.

Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that preclude receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan. We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010 and 2022. We compared overall survival (OS) between patients diagnosed from 2010 to 2018, which will be referred to as the historical control era and patients diagnosed from 2019 to 2022, which will be called the aggressive supportive care era. Fifty-four patients were included in our analysis; 31 patients were treated in the historical control time frame, and 23 patients were treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p < 0.01). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p < 0.01). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median OS for historical control patients was 5.4 months as compared with 10.4 months for patients treated during aggressive supportive care era (p = 0.04). Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared with historic controls. Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.

Small-Dose Trimethoprim-Sulfamethoxazole Prevents Pneumocystis Jiroveci Pneumonia in B-Cell Lymphoma Patients Receiving Chemotherapy: Analysis of a Randomized Controlled Clinical Trial

B-cell lymphoma is the most common non-Hodgkin lymphoma and is usually treated with the R-CHOP regimen. However, some patients might develop interstitial pneumonitis (IP), which has led to death in some patients. With advances in detection techniques, infections are now considered to be an important etiologic factor in IP, particularly the common opportunistic causative agent Pneumocystis jiroveci. A retrospective cohort analysis at our center has tentatively elucidated that TMP-SMX can achieve effective IP prevention. There are no prospective studies to confirm the preventive effect of TMP-SMX and its mechanism. A single-arm, single-center, randomized controlled clinical trial of TMP-SMX for the prevention of interstitial pneumonitis was conducted at our center. Prophylactic treatment with TMP-SMX in patients in the treatment group was turned on immediately after starting chemotherapy and continued until one month after the end of chemotherapy. The dose of prophylactic treatment was 0.16 g of TMP/0.8 g of SMX once daily. From April 26, 2022, to July 25, 2023, a total of 198 patients with the diagnosis of B-cell lymphoma met the criteria for enrollment and were randomly assigned to the control and treatment groups. Eleven were lost to follow-up before completing 4 courses of chemotherapy, 19 did not complete 4 courses of chemotherapy as of July 25, 2023, and 3 were excluded from the evaluation when they were switched to chemotherapy with other regimens not based on R-CHOP because of poor efficacy after 1 course of chemotherapy, among other reasons. 80 patients in the treatment group and 85 in the control group were finally included in the assessment (Figure 1, Figure 2). There were no statistical differences between patients in the control and treatment group in terms of baseline clinical characteristics such as gender, age, smoking history, lung disease, type of pathology, Ann Arbor stage, LDH level, ECOG score, IPI score, chemotherapy regimen, and group B symptoms. Observation of the primary outcome events in this study showed a significant reduction in the incidence of IP (5.0% vs 47.1%, P&amp;lt;0.001) and PJP (0.0% vs 28.2%, P&amp;lt;0.001) in the patients in the treatment group (Figure 2). IP occurred in 4 (5.0%) in the treatment group, and retrospective patient characteristics revealed that all were COVID-19, in addition to no patients developing IP. Forty (47.1%) in the control group developed IP, 16 were COVID-19, and 24 patients had a complete bronchoscopy with alveolar lavage sent for NGS, all of which revealed PJs or concomitant other pathogens. As of July 25, 2023, 1 patient discontinued TMP-SMX because of the development of renal insufficiency. There have been no deaths due to PJP in patients enrolled in this clinical trial at our center. The results of the subgroup analyses showed that TMP-SMX prophylaxis in any subgroup significantly reduced the risk of IP and there was no interaction. Of the 44 patients who developed IP, 24 underwent bronchoscopy, and PJ was detected by alveolar lavage NGS in all of them, and other pathogens such as Streptococcus pneumoniae, human herpesvirus, Catamoeba, and Candida albicans were detected in some patients. The median number of chemotherapy cycles in which IP occurred was 4 (Figure 1). In the control group, between patients who developed IP and those who did not, there were statistically significant differences in LDH levels (IP 237.0 (194.5, 398.0) vs Non-IP 198.0 (161.0, 278.0), P=0.032), R-CDOP chemotherapy regimen (IP 67.5% vs Non-IP 42.2%, P=0.004) difference, and the rest of the factors did not differ between the two groups. Binary logistic regression analysis of risk factors for the development of IP in the control group showed that patients on the R-CDOP chemotherapy regimen had a significantly increased risk of IP (OR=2.72, 95% CI 1.09-6.80, P=0.033), whereas there was no significant difference between age and LDH. As the chemotherapy cycle progressed, the patients' CD4 + T-cell counts gradually decreased, with the same trend in the control group as in the treatment group. In patients receiving chemotherapy with R-CHOP/R-CDOP-based regimens, the majority of IP that occurs is PJP and prevention with TMP-SMX is safe and effective. Patients treated with PLD have a higher risk of IP occurrence.

Gestational trophoblastic neoplasia: does centralization of care impact clinical management?

ObjectiveInternational societies advocate for gestational trophoblastic neoplasia referral to designated expert centers. This study assessed the impact of centralization of trophoblastic care on clinical outcomes.MethodsA centralized program was implemented in...

Chemotherapy effect on myocardial fibrosis markers in patients with gynecologic cancer and low cardiovascular risk.

Patients with gynecologic cancers experience side effects of chemotherapy cardiotoxicity. We aimed to quantify cardiac magnetic resonance (CMR) markers of myocardial fibrosis in patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy. This study is part of a registered clinical research. CMR T1 mapping was performed in patients with gynecologic cancer and low cardiovascular risk undergoing chemotherapy. The results were compared with those of age-matched healthy control subjects. 68 patients (median age = 50 years) and 30 control subjects were included. The median number of chemotherapy cycles of patients was 9.0 (interquartile range [IQR] 3.3-17.0). Extracellular volume fraction (ECV) (27.2% ± 2.7% vs. 24.5% ± 1.7%, P < 0.001) and global longitudinal strain (-16.2% ± 2.8% vs. -17.4% ± 2.0%, P = 0.040) were higher in patients compared with controls. Patients with higher chemotherapy cycles (>6 cycles) (n=41) had significantly lower intracellular mass indexed (ICMi) compared with both patients with lower chemotherapy cycles (≤6 cycles) (n=27) (median 27.44 g/m2 [IQR 24.03-31.15 g/m2] vs. median 34.30 g/m2 [IQR 29.93-39.79 g/m2]; P = 0.002) and the control group (median 27.44 g/m2 [IQR 24.03-31.15 g/m2] vs. median 32.79 g/m2 [IQR 27.74-35.76 g/m2]; P = 0.002). Patients with two or more chemotherapy regimens had significantly lower ICMi compared with both patients with one chemotherapy regimen (27.45 ± 5.16 g/m2 vs. 33.32 ± 6.42 g/m2; P< 0.001) and the control group (27.45 ± 5.16 g/m2 vs. 33.02 ± 5.52 g/m2; P < 0.001). The number of chemotherapy cycles was associated with an increase in the ECV (Standard regression coefficient [β] = 0.383, P = 0.014) and a decrease in the ICMi (β = -0.349, P = 0.009). Patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy have diffuse extracellular volume expansion, which is obvious with the increase of chemotherapy cycles. Myocyte loss may be part of the mechanism in patients with a higher chemotherapy load. http://www.chictr.org.cn, identifier ChiCTR-DDD-17013450.

Phase III randomized clinical trial comparing the efficacy of neoadjuvant chemotherapy and standard treatment in patients with locally advanced colon cancer: The NeoCol trial.

LBA3503 Background: Locally advanced colon cancer presents a therapeutic challenge regarding improving survival and minimizing side effects by optimizing the timing of surgical and systemic treatments. Neoadjuvant chemotherapy is a widely accepted approach in numerous cancers as it aims to eliminate micrometastases and reduce tumor size. Our study aimed to assess the impact of neoadjuvant chemotherapy on locally advanced colon cancer compared to standard initial surgery. Methods: This was a randomized, controlled, phase III clinical trial. Patients aged 18 years or older with biopsy-proven colon cancer were eligible for inclusion if staged as T4 or T3 with invasion depth ≥5 mm, N0-2, and M0 according to CT scan evaluation. Patients were randomly assigned to either standard upfront surgery or surgery after neoadjuvant chemotherapy with either 3 cycles of CAPOX (oxaliplatin, capecitabine every 3 weeks) or 4 cycles of FOLFOX (oxaliplatin, 5FU every 2 weeks). Adjuvant chemotherapy was chosen based on the pathological stage of the cancer according to guidelines. The primary endpoint, disease-free survival (DFS), was analyzed on an intent-to-treat basis. The sample size was set at 125 patients per arm, based on a projected increase in two-year disease-free survival from 80% to 90%, with a two-sided significance level of 5%, power of 80%, 3 years of inclusion, 2 years of follow-up, and a 10% drop-out rate. Results: Nine centers in 3 countries included 122 patients in the standard group and 126 patients in the neoadjuvant group from 10/2013 to 11/2021. Forty-four % were female, the median age was 66 years, and 91% had a performance status (PS) of 0, while 9% had a PS of 1. Seventy-three % of the tumors were classified as T3, with a median outgrowth of 11 mm, while 26% were classified as T4 on the baseline CT scan. There were no significant differences in baseline characteristics. The median number of chemotherapy cycles was lower in the neoadjuvant group, 3 (IQR 1-7) vs. 4 (0-8). There were slightly more postoperative complications in the standard group regarding ileus, anastomotic leakage, and length of stay. Postoperatively, more patients in the standard arm had an indication of adjuvant chemotherapy, 88 vs. 72 (p = 0.02). DFS at 2 years was similar in the two arms (p = 0.95, logrank), as was overall survival (OS) (p = 0.95, logrank). Conclusions: Neoadjuvant chemotherapy and standard upfront surgery showed no significant difference in DFS and OS in patients with colon cancer. However, neoadjuvant chemotherapy seemed to have more favorable outcomes in terms of chemotherapy cycles, postoperative complications, and downstaging. CT scan alone may not be sufficient in identifying high-risk patients preoperatively. These findings suggest that neoadjuvant chemotherapy could be considered a viable treatment option for patients with locally advanced colon cancer. Clinical trial information: NCT01918527 .

An audit of neoadjuvant chemotherapy in sinonasal teratocarcinosarcoma from an academic tertiary care centre in India.

e18109 Background: Sinonasal teratocarcinosarcoma (SNTCS) are rare types of sinonasal malignancies, incidence is approximately 3% of all head and neck cancers and less than 1% of all tumors. There is very limited literature available on SNTCS and most of the literature available is in the form of case reports and small case series. The management of these tumors is complicated because of the location and paucity of data available in such scenarios where resection becomes difficult in extensive disease and the role of neoadjuvant chemotherapy (NACT) becomes significant. This audit was performed to study the tolerance and outcomes with NACT followed by surgery(Sx) in these treatment protocols. Methods: A retrospective analysis of a prospectively maintained database approved by the IEC of TMH. The baseline characteristics, extent of tumor, type of NACT, adverse events was curated from the EMR and patients' hospital files. Patients with clinically or radiologically extensive/inoperable disease at presentation were planned for NACT for a duration of 6-8 weeks. Post NACT these patients underwent axial imaging for response assessment.(RECIST v1.1). The adverse events due to NACT were noted as per CTCAE v5.0. Results: There were 27 patients of SNTCS. The median age of the whole cohort was 42 years (IQR 30-56) and 85.2% (n=23) were male. The ECOG PS was 0-1 in 24 (88.8%) patients and only 3 (11.1%) patients had ECOG PS 2. 17 patients (63%) had a history of addiction. 7 patients had clinical palpable regional nodes (25.9%) and 1 patient (3.7%) had lung metastasis at presentation. All 27 patients received NACT in view of extensive disease .15 patients (55.6%) had intracranial extension of disease with intradural extension. Only 10 patients (37%) had intraparenchymal disease. 22 patients (81.5%) had Kadish stage C-D disease and the remaining 5 patients (18.5%) had Kadish stage B at baseline. 20 patients (74.1%) received Cisplatin &amp; Etoposide as NACT and remaining 7 received other chemotherapy. Median number of chemotherapy cycles was 2 (Q1 is 2 - Q3 is 3). 1 patient (3.7%) did not complete the planned NACT due to toxicity. The incidence of grade 3-5 toxicity in accordance with CTCAE version 5.0 was 37.03%. There was 1 death (3.7%) due to chemotherapy toxicity. Details of response to NACT are given in the table. 18 patients (77.8%) underwent Sx, 5 patients (18.5%) received CTRT and 2 patients (7.4%) received definitive RT and 2 patients (7.4%) did not receive any local therapy .Post Sx in local node was found in 3 patients (11.11%).The 2 years progression free survival was 53.2%(95%CI 31.3 - 70.9) and 2 years overall survival was 60.9%(95%CI 37.6 - 77.8). Conclusions: NACT improves survival in locally advanced SNTC with significant response rates. [Table: see text]

Randomized placebo-controlled trial of intravenous vitamin C plus docetaxel in metastatic prostate cancer.

e17050 Background: Some phase I/II trials showed that combining high dose IV vitamin C with chemotherapies decreased toxicities and improved QoL in advanced cancers, while others failed to show benefits. While grade ¾ AEs are not typically a co-primary endpoint, they are a measure of cumulative toxicity. We investigated whether high-dose IV vitamin C could improve prostate-specific antigen (PSA) response rate and mitigate docetaxel toxicities in patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving docetaxel. Methods: Patients were randomized (2:1) to receive docetaxel (75mg/m2 IV every 3 weeks) plus IV vitamin C (1g/kg) or placebo twice a week. The primary endpoints were PSA50 response by24 weeks and adverse events (AEs) of fatigue, nausea, bone pain, and anorexia. Secondary endpoints included overall survival (OS) and QoL measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Results: 50 patients were randomized, 47 received therapy (treatment N = 32, control N = 15), 3 untreated (withdrawal, elevated creatine, low hemoglobin). The median age was 74 years (range 45-85) and ECOG 1. The median PSA was 108.3 ng/mL (range: 0.3, 2102.3). The median number of chemotherapy cycles was 6 (IQR 3-8). The study was suspended after the pre-specified interim analysis for primary endpoints showed futility. The PSA50 response was 41% for treatment and 33% for control (P = 0.44). Grade 1-2 and grade 3-4 prespecified AEs occurred in 69% and 6% of treatment group patients versus 60% and 0% of control group patients (one-sided Cochran Armitage test, P =0.90). Diarrhea (72% vs 19%) and anemia (47% vs 25%) and neutropenia (22% vs 19%) are more frequent in the Vit C group. Compared with the control group, treatment group patients showed a trend towards shorter median OS. FACT-P was not significantly different at any timepoints. Conclusions: Initial concurrent high-dose IV vitamin C with docetaxel did not improve PSA response, toxicity, or clinical outcomes. MCRPC patients receiving docetaxel should be advised against seeking concurrent high-dose IV vitamin C. Clinical trial information: NCT02516670 .

Outcomes for immuno-chemotherapy based treatment in patients with poorly differentiated extrapulmonary neuroendocrine carcinoma.

e14619 Background: Extrapulmonary neuroendocrine carcinoma (EP-NEC) represents a rare collection of neuroendocrine cancers characterized with a poor prognosis and modest treatment benefit similar to small cell lung carcinoma (SCLC). Platinum-based chemotherapy (cisplatin or carboplatin) and etoposide is the preferred 1st line therapy for patients (pts) with metastatic EP-NEC who are not eligible for curative surgery (Frizziero et al. 2019). Studies in pts with advanced SCLC have shown improved progression free survival (PFS) and overall survival (OS) with the addition of atezolizumab, an anti-PD-L1 monoclonal antibody, to induction chemotherapy (4 cycles) versus chemotherapy alone (Horn et al. 2018). Prospective trials investigating immune checkpoint inhibitors such as atezolizumab plus chemotherapy have yet to be published in EP-NEC. Methods: We retrospectively reviewed all registered pts at the Gastrointestinal Medical Oncology Clinic at Banner-University of Arizona Cancer Center who received at least 1 dose of atezolizumab from 1/2017 through 3/2022 (UAIRB00001593). Criteria for pt selection for analysis was based on the following: pts diagnosed with grade III, Ki 67&gt;20%, poorly differentiated, metastatic EP-NEC and treated with ≥ 1 dose of atezolizumab plus chemotherapy as 1st line treatment. Results: Ten pts received atezolizumab based therapy during this timeframe. 6 pts met criteria for analysis and 4 pts were excluded for alternative diagnoses. 4 pts were female, 2 pts were male, and the average age at diagnosis was 63.8 years. The median number of chemotherapy cycles was 7.0 [4-17]. The median number of atezolizumab doses was 7.5 [6-28]. The median PFS was 7 months (95% CI 5-*). The median overall survival (mOS) was 13 months (95% CI 8-*). The mOS since starting atezolizumab was 12 months (95% CI 8-*). [*Upper bound of 95% CI cannot be determined.] Five pts (83%) demonstrated a partial response per RECISTv1.1. All pt tumors were MMR-proficient/MSI-stable and PD-L1 expression was negative in 3 pts (PD-L1 status unavailable for 3 pts). No hospitalizations related to immunotherapy or chemotherapy were observed. The most common adverse events included nausea, diarrhea and fatigue. One immune-mediated adverse event of thyroid dysfunction was observed and successfully medically managed. Conclusions: Our experience with atezolizumab plus chemotherapy for 1st line EP-NEC pts demonstrated efficacy via high response rate and survival rates above historical experience. Continuing chemotherapy beyond the induction phase until maximum clinical response demonstrated tolerability with manageable side effects. Although the scope is limited due to sample size, this data supports further investigation of this combination. There is an ongoing large, randomized, prospective trial investigating this regimen in frontline, metastatic EP-NEC pts ( NCT05058651 ).

Abstract P3-06-03: Trilaciclib induces immune changes within the tumor microenvironment in early-stage triple-negative breast cancer

Abstract Background: In early-stage triple-negative breast cancer (TNBC), there is accumulating evidence of a correlation between tumor-infiltrating lymphocytes in tumor tissue and favorable clinical outcomes, with a high CD8+/regulatory T-cell (Treg) ratio after neoadjuvant chemotherapy being predictive of overall survival and associated with pathologic complete response (Ladoire S, et al. Br J Cancer. 2011; Park YH, et al. Nat Commun. 2020). Trilaciclib is a transient inhibitor of cyclin-dependent kinase 4/6 that is administered intravenously prior to chemotherapy. In preclinical studies, trilaciclib has been shown to have immune-enhancing effects by differentially arresting CD8+ T-cell and Treg subsets, which is followed by the faster recovery of CD8+ T cells than Tregs in the tumor microenvironment. Methods: This phase 2, single-arm, open-label study aims to evaluate neoadjuvant, single-dose trilaciclib followed by trilaciclib plus dose-dense anthracycline/cyclophosphamide and taxane in patients with early-stage TNBC (NCT05112536). Patients with previously untreated, non-metastatic, confirmed TNBC and a primary tumor ≥ 1.5 cm of any nodal status receive a single dose of trilaciclib 240 mg/m2 during the lead-in phase, followed by 4 cycles of doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2, and 12 weekly cycles of paclitaxel 80 mg/m2. Trilaciclib 240 mg/m2 is administered prior to the first chemotherapy dose of each cycle. Pembrolizumab 400 mg every 6 weeks starting on day 1, cycle 1, and/or carboplatin AUC 1.5 every week starting on day 1, cycle 5, is allowed per investigator discretion. Tumor biopsies and peripheral blood samples are collected prior to any treatment, 7 days ± 1 day post administration of trilaciclib, and during surgery, with an additional blood sample collection on day 1, cycle 2. The primary objective is to evaluate the immune-based mechanism of action of trilaciclib after a single dose of trilaciclib, as measured by changes in the CD8+/Treg ratio in tumor tissue. Pathologic complete response, safety and tolerability, and additional exploratory immune biomarker endpoints will also be assessed. Results: As of June 3, 2022, 9 patients with early-stage TNBC had been enrolled and 8 patients had received the trilaciclib lead-in dose and initiated doxorubicin/cyclophosphamide. Patients had a median age of 53.0 years, and all had stage II tumors at diagnosis, with 7 having ductal carcinoma. The median number of chemotherapy cycles received was 3 (range 1–6), and all 8 patients received pembrolizumab. Seven patients continue study treatment; 1 patient discontinued due to disease progression. Five patients had an adverse event (AE) related to any study treatment, including 4 patients with ≥ 1 trilaciclib-related AE. There were no grade ≥ 3 treatment-related AEs or serious AEs. On-treatment, post-trilaciclib monotherapy biopsies were available for 4 patients. Following neoadjuvant trilaciclib treatment, the median density of stromal CD8+ T cells increased from 103.1/mm2 at baseline to 229.8/mm2 at day 7. The median CD8+/Treg ratio increased in 2 patients from 1.85 at baseline to 1.90 at day 7. Conclusions: Preliminary analysis of on-treatment tumor biopsies from 4 patients suggests that a single dose of trilaciclib may modulate the immune cell composition in the tumor microenvironment to support antitumor immune responses. The increase in CD8+ T cells following 7-day neoadjuvant treatment with trilaciclib supports previous data suggesting a role in T-cell infiltration. The complete dataset from all patients (estimated enrollment: N ≈ 24) and additional biomarker analyses will be presented. Citation Format: Michael Danso, Joyce O’Shaughnessy, Lisa S. Wang, Kailash Mosalpuria, Sara Hurvitz, Shom Goel, Sarah Ahn, Subing Cao, John S. Yi, Taofik Oyekunle, Amanda Jacobson, Andrew Beelen, Jeremy Force. Trilaciclib induces immune changes within the tumor microenvironment in early-stage triple-negative breast cancer [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 P3-06-03.

Therapeutic efficacy of platinum/etoposide regimens in the treatment of advanced poorly differentiated neuroendocrine carcinomas of the lung: A retrospective analysis.

Lung neuroendocrine neoplasms (NENs) are rare malignancies developed from bronchial mucosa. Because of its rarity and complex histopathology, there is limited data on the role of chemotherapy in this subset of tumors. Few studies regarding the treatment of poorly differentiated lung NENs, known as neuroendocrine carcinomas (NECs), are available and many limits are detectable as heterogeneity of tumor samples including different origins and different clinical behaviors, moreover, no evidence of therapeutic advances have been achieved along the last thirty years. We performed a retrospective analysis of 70 patients affected by poorly differentiated lung NECs: half of patients underwent a first line therapy with a combination of cisplatin plus etoposide; the remaining patients receiving carboplatin instead of cisplatin, plus etoposide. Results: In our analysis, the outcomes of patients treated with either cisplatin or carboplatin schedule are similar in terms of ORR (44% versus 33%), DCR (75% versus 70%), PFS (6.0 versus 5.0 months) and OS (13.0 versus 10 months). Median number of chemotherapy cycles was 4 (range 1-8). The 18% of patients required a dose reduction. Main toxicities reported were hematological (70.5%), gastrointestinal (26.5%) and fatigue (18%). Survival rate in our study suggests that high grade lung NENs are characterized by an aggressive behavior and a poor prognosis, despite the treatment with platinum/etoposide according to available data. Clinical results of present study contribute to strengthen available data on the usefulness of platinum/etoposide regimen in the treatment of poorly differentiated lung NENs.

The High Incidence of Occult Carcinoma in Total Hepatectomy Specimens of Patients Treated for Unresectable Colorectal Liver Metastases With Liver Transplant.

To describe the rate of occult carcinoma deposits in total hepatectomy specimens from patients treated with liver transplant (LT) for colorectal liver metastases (CRLM). Previous studies have shown that patients with CRLM treated with systemic therapy demonstrate a high rate of complete radiographic response or may have disappearing liver metastases. However, this does not necessarily translate into a complete pathologic response, and residual invasive cancer may be found in up to 80% of the disappearing tumors after resection. Retrospective review of 14 patients who underwent LT for CRLM, at 2 centers. Radiographic and pathologic correlation of the number of tumors and their viability before and after LT was performed. The median (interquartile range) number of tumors at diagnosis was 11 (4-23). The median number of chemotherapy cycles was 24 (16-37). Hepatic artery infusion was used in 5 patients (35.7%); 6 (42.9%) underwent surgical resection, and 5 (35.7%) received locoregional therapy. The indication for LT was unresectability in 8 patients (57.1%) and liver failure secondary to oncologic treatment in the remaining 6 (42.9%). Before LT, 7 patients (50%) demonstrated fluorodeoxyglucose-avid tumors and 7 (50%) had a complete radiographic response. Histopathologically, 11 patients (78.6%) had a viable tumor. Nine (64.2%) of the 14 patients were found to have undiagnosed metastases on explant pathology, with at least 22 unaccounted viable tumors before LT. Furthermore, 4 (57.1%) of the 7 patients who demonstrated complete radiographic response harbored viable carcinoma on explant pathology. A complete radiographic response does not reliably predict a complete pathologic response. In patients with unresectable CRLM, total hepatectomy and LT represent a promising treatment options to prevent indolent disease progression from disappearing CRLM.

Long telomeres at baseline and male sex are main determinants of telomere loss following chemotherapy exposure in lymphoma patients.

Although chemotherapy (CHT) exposure is an established cause of telomere attrition, determinants of telomere length (TL) dynamics after chemotherapy are poorly defined. In this study, we analyzed granulocyte telomere dynamics in 34 adult lymphoma patients undergoing first-line CHT. TL was measured by southern blot at each CHT cycle and after 1year from CHT completion. Median age was 59yrs (range 22-77). Median number of CHT cycles was 6 (range 3-6). The majority of patients (79%, n=27) experienced TL shortening following CHT exposure. Mean telomere loss was 673 base pairs (bp) by cycle 6. Telomere shortening was an early event as 87% of the total telomere loss (mean 586 bp) occurred by the end of cycle 3, with no significant recovery after 1year. A significant correlation was observed between baseline TL and total or fractional telomere loss (p<0.001), with telomere shortening by cycle 3 observed predominantly in male patients with long telomeres at pre-treatment evaluation. Stratifying the analysis by gender and age only young women (<51years of age) did not show significant telomere shortening following chemotherapy exposure. These findings indicate that gender and baseline TL are major determinants of TL dynamics following chemotherapy exposure in lymphoma patients.

Real-World Treatment Outcomes and Toxicities of Outpatient R-CHOP/R-DHAP in Patients with Mantle Cell Lymphoma Eligible for Autologous Stem Cell Transplant

INTRODUCTION: Despite a significant increase in median overall survival (OS) over the past three decades, mantle cell lymphoma (MCL) remains incurable with no standard frontline therapy. The addition of R-DHAP to R-CHOP with autologous stem cell transplant (ASCT) in the European MCL Network - MCL younger trial showed significant improvement in median progression free survival (PFS), although some concerns remain regarding increased toxicity. On this basis, R-CHOP/R-DHAP was approved as first line therapy for MCL at CancerCare Manitoba (CCMB) in 2016. In contrast to the original study, R-DHAP is currently administered in an outpatient setting in Manitoba. OBJECTIVE: To assess the real-world, non-trial PFS, OS, and toxicities of patients with MCL eligible for autologous stem cell transplant receiving R-CHOP/R-DHAP, administered on an outpatient basis, as induction therapy in Manitoba. METHODS: All patients with MCL in Manitoba eligible for R-CHOP/R-DHAP induction between Jan 1, 2016 and Dec 31, 2021 were identified through the CCMB. Individual patient records were obtained and reviewed for baseline demographic data, laboratory data, treatment characteristics including response, and treatment toxicities. SPSS was then used for statistical analysis to calculate PFS and OS using the Kaplan-Meier method. RESULTS: 25 charts were identified. 5 were excluded based on duplicate data for a total of 20 patients (85% male). The mean age at diagnosis was 54.4 (range 42-67). 75% had stage IV disease and 35% had constitutional symptoms. 15% of patients had ECOG ≥2 at diagnosis. 50% had elevated LDH at diagnosis, and the mean β-2-microglobumin was 3.5mg/L (range 1.9-16.1). 10% of patient's largest nodal dimension was >=7.5cm, 20% had disease with Ki67>=40%, and 15% had high risk disease by MIPI. The median number of chemotherapy cycles completed was 6 (range 2-6), with 50% requiring modification to therapy (5% progression, 20% infection, 20% ototoxicity, 20% nephrotoxicity, 5% corneal toxicity, 5% patient preference). 70% received ASCT, with 100% complete response by PET post-ASCT. 75% of all patients received maintenance rituximab, with a median of 8 cycles completed (range 2-8). At the end of follow up, there were 3 progression events, 3 deaths, and 1 death attributed to MCL. At a median follow up of 56.8 months, median PFS and OS were not reached. CONCLUSION: Our real-world data show feasibility of administering R-CHOP/R-DHAP in the outpatient setting with comparable outcome and toxicities to original study where R-DHAP was administered as inpatient. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ABCL-398 Primary Breast Diffuse Large B-Cell Lymphoma: An Indian Experience

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare site of localized extranodal DLBCL. It represents 0.5% of all primary malignant neoplasms of the breast and around 2% of extranodal lymphomas. There is a paucity of data regarding the clinicopathologic characteristics, cell of origin, response, and outcome of treatment with uniform treatment protocol in patients from India diagnosed with PB-DLBCL. This was a retrospective study of 18 consecutive cases of PB-DLBCL registered at All India Institute of Medical Sciences between 2006 and 2021 treated with uniform 3x weekly cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) ±rituximab (R) with involved-field radiotherapy. The patients were classified as germinal center B-cell-like or activated B-cell (ABC) type using the Hans classification. The median age was 43 (21-67) years with a male:female ratio of 1:17. All the patients presented with a breast lump with a median tumor size of 5 cm. The right side was involved in 11 (61.1%) cases. Eight patients were diagnosed with lumpectomy, 9 patients with biopsy, and one patient with mastectomy specimen. Out of 18 patients, Ann Arbor: Stage I was seen in 6 (33.3%) patients, Stage IIE in 11 (61.1%) patients, and Stage 1V in 1 (5.5%) patient. B-symptoms and bulky disease were seen in 6 (33.3%) and 7 (38.8%) patients, respectively. Cell of origin data were available in 14 patients, and 11 (71.4%) were ABC in origin. Low- and intermediate-risk International Prognostic Index was seen in 42% and 48% of patients, respectively. The median number of chemotherapy cycles was 4 (3-6), rituximab was used in 10 (55.5%) cases, and CNS prophylaxis with intrathecal methotrexate was used in 10 (55.5%) cases. The complete response rate was 83.3%. After a median follow-up of 42 months, the 3-year progression-free survival and overall survival were 75% and 88%, respectively. The most common site of relapse (n=3) was parenchymal brain disease. Multimodality combination therapy (chemotherapy, immunotherapy, and radiation) can give good survival with PB-DLBCL but adding high-dose methotrexate to existing protocol needs further exploration.

Dose intensity and outcomes of VDC/IE chemotherapy for adolescent and adult patients with Ewing’s family sarcoma.

11570 Background: Ewing’s family sarcoma (EFS) is a rare and aggressive malignancy with peak incidence in the second decade of life. Treatment is multimodal, involving local surgery and/or radiotherapy, and chemotherapy, typically with VDC/IE (Vincristine, Doxorubicin, Cyclophosphamide alternating with Ifosfamide, Etoposide). There is paucity of data in the adult setting, with treatment protocols extrapolated mainly from the paediatric setting. We assessed chemotherapy dose intensity and outcomes across four Australian sarcoma centres (three adult and one paediatric centre). Methods: Using the Australia New Zealand Sarcoma Association national database (ACCORD) and medical records, we identified patients aged ≥10 years diagnosed with EFS between 2010-2020. Clinical characteristics, treatment and survival information were collected for those receiving Ewing protocol with VDC/IE backbone. Received Dose Intensity (RDI) of chemotherapy was calculated using planned and actual doses received and time taken. RDI ≥85% was considered acceptable, consistent with published literature. We compared survival outcomes based on RDI. Clinical predictors of achieving an acceptable RDI were explored using logistic regression. Results: Of 146 patients with EFS identified, 76 received VDC/IE (59% male). The median age was 25 years, with age distribution 24% aged 10-19, 58% aged 20-39, and 18% aged 40-59. Majority had extraskeletal Ewing’s (57%), non-extremity primary site (64%) and localised disease (stage, II 37%; III 28%; IV 28%). Treatment received included surgery (74%), radiotherapy (66%) and chemotherapy (100%). Over two-thirds (70%) completed their scheduled chemotherapy and 57% achieved an acceptable RDI (67% aged 10-19, 61% aged 20-39, 29% aged 40-59). Compared to those aged 10-19, the odds ratio (OR) of an acceptable RDI for patients aged 20-39 was 0.79 (95% CI 0.24-2.46, p = 0.70) and for patients aged 40-59 was 0.20 (95% CI 0.04-0.86, p = 0.04). The median number of chemotherapy cycles was 14 (range, 2-17). Dose reductions were mostly within 20% cumulative target dose (91%), and were predominantly for neutropenia (47%), thrombocytopenia (30%) and/or anaemia (28%), and less frequently for cardiotoxicity (7%). Median follow-up was 37.3 months. Two-year progression-free survival (PFS) rates were 56% for acceptable RDI, compared to 30% for low RDI (p = 0.001), with two-year overall survival (OS) rates respectively 88% versus 49% (p &lt; 0.001). After adjustment for age, gender, Ewing’s type, primary site and stage, RDI remained an important prognostic factor (PFS HR 0.39, 95% CI 0.18-0.82; OS HR 0.25, 95% CI 0.10-0.63). Conclusions: Survival outcomes in EFS were contingent on achieving an acceptable RDI. It was more difficult to maintain VDC/IE chemotherapy dose intensity in adults aged over 40 years, due to myelosuppression. Optimal treatment strategy for older adults remains to be defined.

MO311: Acute Kidney Injury in Leukaemia Patients Submitted to Allogeneic Haematopoietic Stem Cell Transplant—Incidence and Risk Factors: A Cohort Analysis

Abstract BACKGROUND Studies on acute kidney injury (AKI) in hematopoietic stem cell transplant (HSCT) consider several haematologic diagnoses in their cohorts and heterogeneous definitions for AKI not taking into consideration urinary output (UO). We aimed to evaluate the incidence and risk factors of the first AKI episode in patients with leukaemia submitted to allogeneic HSCT occurring in the first 100 days post-HSCT, considering both SCr and UO criteria in KDIGO classification. METHODS We conducted a single-center retrospective cohort study, including patients with leukaemia admitted for allogeneic HSCT between 2005 and 2015. KDIGO classification was used for AKI diagnosis considering daily values of SCr and 6-h UO from admission day for HSCT until hospital discharge, and weekly evaluations within the first 100 days beyond hospital discharge. To estimate AKI cumulative incidence and to establish AKI risk factors, survival analysis methods considering death as a competing risk were used. RESULTS A total of 164 patients, 54.3% female, 91.5% Caucasian, median age 39.1 (P25 = 28.1–P75 = 50.4), body mass index 23.2(20.9–25.3), HCT-CI (haematopoietic cell transplantation-specific comorbidity index) &amp;lt; 2 in 85.4% of patients. Of them, 55.5% had acute myeloid leukaemia, 33.5% had acute lymphoblastic leukaemia, 8.5% had chronic myeloid leukaemia and 2.4% had rare forms of leukaemia. A total of 6.7% had been submitted to radiotherapy in the past, median number of chemotherapy cycles was 3 (2–4). A total of 71.3% were prescribed a reduced-intensity conditioning regimen, 56.1% had a related donor and peripheral blood was the source of progenitor cells in 13.4%. In the 100 days post-HSCT, 89.6% developed sepsis, 82.9% were exposed to nephrotoxic drugs, 39.0% had hypovolemia, 25.0% complicated with shock and 7.9% went to intensive care unit. A total of 71.3% developed graft versus host disease, 32.3% registered cytomegalovirus infection. The cumulative incidence of AKI was 58.5% at 30 days post-HSCT and 63.4% at 100 days post-HSCT. AKI diagnosis was first made by SCr criteria in 76.9%, by UO criteria in 15.4% and by both in 7.7%. The highest stage of AKI was 1 in 61.8%, 2 in 21.6% and 3 in 16.7%. A total of 12.5% underwent renal replacement therapy. In our multivariable model, variables independently associated with a higher incidence of AKI were: HCT-CI &amp;lt; 2 [HR 1.88, 95% confidence interval (95% CI) 1.13–3.11; P = .015], previous radiotherapy (HR 2.07, 95% CI 1.06–4.03; P = .034), shock (HR 1.57, 95% CI 1.02–2.39; P = .039), LDH (HR 1.51, 95% CI 1.03–2.21; P = .035) and sepsis (HR 3.36, 95% CI 1.22–9.24; P = .019). CONCLUSIONS AKI incidence affects almost two-thirds of patients with acute and chronic leukaemia submitted to allogeneic HSCT. More than 25% of AKI patients reach stages 2–3. HCT-CI, previous radiotherapy, shock, LDH and sepsis are important independent AKI risk factors. This should bring the attention to the need of developing prevention strategies towards these aspects. This is the first study considering both SCr and UO for defining AKI by KDIGO classification in HSCT, as well as focusing specifically on patients with leukaemia. This approach contributes for a more accurate evaluation and bias reduction.