Perioperative FLOT in elderly patients with resectable gastric cancer: Subgroup analysis from the observational RealFLOT study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4548-4548
Author(s):  
Elisa Giommoni ◽  
Ferdinando De Vita ◽  
Irene Pecora ◽  
Francesco Iachetta ◽  
Antonia Strippoli ◽  
...  

4548 Background: The treatment strategy for patients with resectable gastric cancer changed in the last few years with perioperative treatments. FLOT regimen (fluorouracil, oxaliplatin, docetaxel) turned out to be feasible and effective, offering significant improvement in survival outcomes. However, the safety profile of triplet therapies for elderly patients deserves a special attention and, consequently, the best treatment strategy for these patients is still debated. Methods: Focusing on the elderly patient population (age ≥65 years), real-world data from patients with resectable gastric or gastro-oesophageal junction (GEJ) adenocarcinoma (T≥2 and/or N+) enrolled in the observational RealFLOT study were collected. Results: A total of 206 patients with resectable gastric or GEJ adenocarcinoma received perioperative FLOT at 15 Italian centers in routine clinical practice, between September 2016 and September 2019. The median age was 63 years (range 36-77) and 43% of patients enrolled (n = 89) were ≥65 years. Among elderly patients, 46 (52%) received FLOT for at least 4 full-dose cycles in the preoperative phase, 82 (92%) underwent surgery, and 56 (62%) started the postoperative phase. The primary end point of the study, pathological complete response (pCR) rate, was similar among patients aged ≥65 and < 65 (6.7% vs 7.7%, respectively). The distribution of pathological stages did not differ according to age (p = 0.473), and disease-free survival (DFS) is unrelated to the age of patients (log-rank 0.57; p = 0.89). The incidence of grade (G) 3-4 adverse events (AEs) was similar in the two age groups (Table) and the 30-day mortality rates after surgery did not differ according to age. Conclusions: FLOT regimen demonstrated to be feasible and safe in elderly patients since no differences were observed in terms of pCR, DFS and safety profile according to age. [Table: see text]

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 300-300
Author(s):  
Elisa Giommoni ◽  
Ferdinando De Vita ◽  
Irene Pecora ◽  
Francesco Iachetta ◽  
Antonia Strippoli ◽  
...  

300 Background: Perioperative treatments have significantly improved survival in patients with resectable gastric cancer, increasing 5-year overall survival from 23% with surgery alone to 45% with FLOT (fluorouracil, oxaliplatin, docetaxel). Pathological regression is a prognostic marker of better survival. Methods: In this observational, retro- and prospective study we collected data from patients with resectable gastric or gastro-oesophageal junction (GEJ) adenocarcinoma treated, as clinical practice, with perioperative FLOT. All patients had clinical T2 or higher and/or nodal involvement, according to FLOT4-AIO trial. Results: A total of 206 patients received perioperative chemotherapy with FLOT at 15 Italian centres, between September 2016 and September 2019. Overall, 186 (90.3%) patients completed the preoperative phase, 190 (92%) underwent surgery, and 142 (68.9%) started the postoperative phase. Among patients who started the postoperative phase, 105 (51.0%) received FLOT, while 37 (18%) received less intensive regimens (e.g. FOLFOX or De Gramont), depending on performance status after surgery or toxicity in the preoperative phase. Pathological complete response (pCR) was obtained in 7.3% of cases. In the preoperative phase, grade (G) 3-4 hematological and gastrointestinal adverse events (AEs) were reported in 42 (20.4%) and 13 (6.3%) patients, respectively. Conclusions: These real data confirmed the feasibility of perioperative FLOT in a less-selected population, representative of the clinical practice. The pCR rate was lower than in the FLOT4-AIO trial. The survival outcomes, potential predictive or prognostic factors and comprehensive safety data will be included in the final analysis. [Table: see text]


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14724-e14724
Author(s):  
Michael E. Barfield ◽  
Brian R. Untch ◽  
Justin T. Arcury ◽  
Brian G. Czito ◽  
Christopher Willett ◽  
...  

e14724 Background: Outcomes are poor in patients with gastric cancer, and recurrence is common. Perioperative chemotherapy and adjuvant chemoradiation therapy (CRT) improve survival in patients with resectable disease. Experience with neoadjuvant CRT for potentially resectable disease is limited, and its role remains undefined. We report our experience using neoadjuvant CRT for potentially resectable gastric cancer. Methods: An IRB-approved, retrospective review from 1994 to 2007 identified 23 patients with biopsy-proven, potentially resectable gastric cancer. Patients had T2/T3 and/or N1 disease and no evidence of metastatic disease by endoscopic ultrasound and cross-sectional imaging. All underwent neoadjuvant external beam radiation with concurrent 5-FU or platinum-based chemotherapy followed by restaging and surgery if appropriate. Results: Of the 23 patients, 20 completed neoadjuvant CRT and surgical exploration. Two patients (n=2) had radiographic disease progression during neoadjuvant CRT and did not undergo resection. One patient (n=1) developed a perforated gastric ulcer during CRT and underwent emergent resection. The median time from diagnosis to surgery and completion of neoadjuvant CRT to surgery was 104 days and 37.5 days, respectively. Gastrectomy was performed in 17 (85%) patients who completed neoadjuvant CRT. Metastatic disease was identified in the remaining 3 (15%) patients. Following gastrectomy, a complete pathologic response was observed in 4 (23.5%) patients, a partial response in 11 (64.7%) patients, and no response was identified in 2 (11.8%) patients. One (6%) patient had microscopic positive margins, and 9 (53%) had positive lymph nodes. There was no perioperative mortality. Two (11.8%) patients had anastomotic leaks, which were managed non-operatively. The median length of stay was 10 days. The median disease-free survival was 10.5 months, and median overall survival was 19.6 months. Conclusions: Gastric cancer carries a poor prognosis. Surgical resection after neoadjuvant CRT has low treatment-associated morbidity and mortality. Survival and complete response rates are comparable to published series. Further evaluation of this treatment strategy is warranted to assess its efficacy.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elisa Giommoni ◽  
Daniele Lavacchi ◽  
Giuseppe Tirino ◽  
Lorenzo Fornaro ◽  
Francesco Iachetta ◽  
...  

Abstract Background Perioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) has recently become the gold standard treatment for fit patients with operable gastric (GC) or gastroesophageal (GEJ) adenocarcinoma, getting a 5-year overall survival (OS) of 45%, over 23% with surgery alone. Methods RealFLOT is an Italian, multicentric, observational trial, collecting data from patients with resectable GC or GEJ adenocarcinoma treated with perioperative FLOT. Aim of the study was to describe feasibility and safety of FLOT, pathological complete response rate (pCR), surgical outcomes and overall response rate (ORR) in an unselected real-world population. Additional analyses evaluated the correlation between pCR and survival and the prognostic role of microsatellite instability (MSI) status. Results Of 206 patients enrolled that received perioperative FLOT at 15 Italian centers, 124 (60.2%) received at least 4 full-dose cycles, 190 (92.2%) underwent surgery, and 142 (68.9%) started the postoperative phase. Among patients who started the postoperative phase, 105 (51.0%) received FLOT, while 37 (18%) received de-intensified regimens, depending on clinical condition or previous toxicities. pCR was achieved in 7.3% of cases. Safety profile was consistent with literature. Neutropenia was the most common G 3–4 adverse event (AE): 19.9% in the preoperative phase and 16.9% in the postoperative phase. No toxic death was observed and 30-day postoperative mortality rate was 1.0%. ORR was 45.6% and disease control rate (DCR) was 94.2%. Disease-free survival (DFS) and OS were significantly longer in case of pCR (p = 0.009 and p = 0.023, respectively). A trend towards better DFS was observed among MSI-H patients. Conclusions These real-world data confirm the feasibility of FLOT in an unselected population, representative of the clinical practice. pCR rate was lower than expected, nevertheless we confirm pCR as a predictive parameter of survival. In addition, MSI-H status seems to be a positive prognostic marker also in patients treated with taxane-containing triplets.


Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 80 ◽  
Author(s):  
Tom van den Ende ◽  
Emil ter Veer ◽  
Mélanie Machiels ◽  
Rosa Mali ◽  
Frank Abe Nijenhuis ◽  
...  

Background: Alternatives in treatment-strategies exist for resectable gastric cancer. Our aims were: (1) to assess the benefit of perioperative, neoadjuvant and adjuvant treatment-strategies and (2) to determine the optimal adjuvant regimen for gastric cancer treated with curative intent. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to August 2017 for randomized-controlled-trials on the curative treatment of resectable gastric cancer. We performed two network-meta-analyses (NMA). NMA-1 compared perioperative, neoadjuvant and adjuvant strategies only if there was a direct comparison. NMA-2 compared different adjuvant chemo(radio)therapy regimens, after curative resection. Overall-survival (OS) and disease-free-survival (DFS) were analyzed using random-effects NMA on the hazard ratio (HR)-scale and calculated as combined HRs and 95% credible intervals (95% CrIs). Results: NMA-1 consisted of 9 direct comparisons between strategies for OS (14 studies, n = 4187 patients). NMA-2 consisted of 16 direct comparisons between adjuvant chemotherapy/chemoradiotherapy regimens for OS (37 studies, n = 10,761) and 14 for DFS (30 studies, n = 9714 patients). Compared to taxane-based-perioperative-chemotherapy, surgery-alone (HR = 0.58, 95% CrI = 0.38–0.91) and perioperative-chemotherapy regimens without a taxane (HR = 0.79, 95% CrI = 0.58–1.15) were inferior in OS. After curative-resection, the doublet oxaliplatin-fluoropyrimidine (for one-year) was the most efficacious adjuvant regimen in OS (HR = 0.47, 95% CrI = 0.28–0.80). Conclusions: For resectable gastric cancer, (1) taxane-based perioperative-chemotherapy was the most promising treatment strategy; and (2) adjuvant oxaliplatin-fluoropyrimidine was the most promising regimen after curative resection. More research is warranted to confirm or reproach these findings.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7553-7553 ◽  
Author(s):  
M. Fruh ◽  
H. Tribodet ◽  
J. Pignon ◽  
T. Winton ◽  
T. Le Chevalier ◽  
...  

7553 Background: Adjuvant cisplatin-based chemotherapy (CT) has been shown to increase survival in NSCLC, but uncertainty exists concerning its efficacy and toxicity in elderly patients (≥ 70). Methods: We performed a pooled analysis using individual patient data from 4,584 patients in the LACE database with resected stage IA-III NSCLC enrolled in 5 randomized trials, comparing postoperative CT to no CT (ALPI, ANITA, BLT, IALT and JBR10). Patient and treatment characteristics, CT toxicity and delivery, overall survival, disease-free survival (DFS) and cause-specific mortality were compared among 3 age groups: 3,269 (71%) young (<65), 901 (20%) mid-category (65–69) and 414 (9%) elderly (≥70). The analysis was performed on an intent-to-treat basis. Cox models stratified by trials and adjusted for age, associated drug, planned radiotherapy, total dose of cisplatin (<300, 300, >300), gender, stage, performance status, type of surgery and histology were used with a test for trend to study the effect of CT on survival according to age. Results: Baseline characteristics differed among the age groups, but this was due mainly to the different trial populations and designs. No difference in severe toxicity rate was observed among the age groups. Elderly patients received significantly smaller total doses of cisplatin than the other patients (Chi2-test: p<0.0001) and also the cisplatin doses received were more often lower than the planned one (Kruskal-Wallis test: p<0.0001). The Hazard ratio (HR) of death for the young patients was 0.82 (95% CI 0.73–0.92), 0.86 (95% CI 0.70–1.07) for the mid category and 1.01 (95% CI 0.78–1.32) for elderly patients (test for trend: p=0.17). The HR for DFS was 0.79 (95% CI 0.71–0.87) for the young, 0.76 (95% 0.62–0.93) for the mid category and 0.94 (95% CI 0.73–1.22) for the elderly patients (test for trend: p=0.35). More elderly patients died from non- lung cancer related causes (10% young, 16% mid category and 20% elderly; p<0.0001). Conclusions: The survival benefit from cisplatin-based adjuvant therapy for NSCLC patients was not significantly different according to age, but this may be due to lack of power. Supported by unrestricted grants from PHRC and LNCC No significant financial relationships to disclose.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8026-8026
Author(s):  
Thierry Facon ◽  
Philippe Moreau ◽  
Thomas G. Martin ◽  
Ivan Spicka ◽  
Albert Oriol ◽  
...  

8026 Background: A prespecified interim efficacy analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib (K) and dexamethasone (d) (Isa-Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (HR 0.531; 99% CI, 0.318–0.889; P=0.0007), with a clinically meaningful increase in minimal residual disease negativity (MRD-) (29.6% vs 13.0%) and complete response (CR) (39.7% vs 27.6%) rates, and a manageable safety profile. This subgroup analysis of IKEMA examined efficacy and safety in pts aged <70 and ≥70 years. Methods: Pts with 1–3 prior lines of therapy were randomized 3:2 to receive Isa-Kd (n=179) or Kd (n=123). The primary end point was PFS, as assessed by an independent response committee. We compared outcomes in pts <70 vs ≥70 years; division into different or additional age groups resulted in smaller sample sizes. Results: Of the 302 randomized pts, 71.5% were aged <70 years (Isa-Kd: 70.9%; Kd: 72.4%) and 28.5% were aged ≥70 years (Isa-Kd: 29.1%; Kd: 27.6%). Consistent with the significant improvement of PFS in the overall population, the addition of Isa to Kd resulted in improved PFS independently of age (Table). The CR, ≥very good partial response (VGPR), and MRD- rates were higher with Isa-Kd vs Kd. Within the Isa-Kd arm, CR rate and ≥VGPR rate were similar in elderly and younger pts. MRD- was observed in 32.3% of younger pts and 23.1% of elderly pts with Isa-Kd. In both arms, Grade ≥3 and serious treatment-emergent adverse events (TEAEs) were more frequently reported in elderly pts vs pts <70 years old (Table). For both age groups, the incidence of Grade ≥3 TEAEs was higher whereas the incidence of serious TEAEs was similar between Isa-Kd and Kd. In the elderly subgroup, 3 (5.9%) pts receiving Isa-Kd and 1 (2.9%) receiving Kd had fatal TEAEs (Isa-Kd, infection; Kd, general health deterioration due to progressive disease). The most common Grade ≥3 TEAEs in pts aged <70 and ≥70 years treated with Isa-Kd vs Kd were hypertension (18.3% vs 17.0% [<70 years] and 25.5% vs 26.5% [≥70 years]) and pneumonia (14.3% vs 9.1% [<70 years] and 21.6% vs 20.6% [≥70 years]). Conclusions: The addition of Isa to Kd improved PFS and quality of response in elderly pts, with a manageable safety profile, consistent with the benefit observed in the overall IKEMA study population. Isa-Kd provides a potential new treatment option for elderly pts with RMM. Funding: Sanofi. Clinical trial information: NCT03275285. [Table: see text]


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1778-1778
Author(s):  
Scott F Huntington ◽  
Mahsa Sharifi ◽  
John P Greer ◽  
David Morgan ◽  
Nishitha Reddy

Abstract Abstract 1778 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of lymphoma diagnosed in the United States. Majority of patients diagnosed with DLBCL are in their seventh decade at the time of presentation. Previous studies demonstrate that relative dose intensity (RDI) is an important prognostic factor for survival in patients with DLBCL. Elderly patients who receive chemotherapy intensity comparable to younger patients demonstrate similar outcomes. In our experience, elderly patients appear to receive lower doses of anthracycline based chemotherapy secondary to significant toxicity, poor performance status, or comorbid conditions. We present our experience of RCHOP chemotherapy in the treatment of DLBCL among octogenarians and nonagenarians. Methods: The study population was selected using the Vanderbilt electronic medical record database. After obtaining IRB approval, 102 patients undergoing RCHOP therapy at a single institution between January 2000 and January 2010 were included in our analysis. Patients who were treated with RCHOP elsewhere were excluded from the study. Pre-treatment co-morbidities were identified and scored using the Cumulative Illness Rating Scale (CIRS). All data was compiled using Research Electronic Data Capture (REDCap). Descriptive statistics and multivariate logistic regression modeling were performed using SPSS software. Results: Of the 102 identified patients, 37 (36%) were aged 70 years or greater with a median age of 79 years (range 70–90). The median age of patients <70 years was 59 years (range 20–70). The majority had a diagnosis of DLBCL while eight (7.8%) patients had follicular grade 3b lymphoma. Differences in baseline BMI and body surface area (BSA) were statistically significant between age groups (70 years or greater: less than 70 years). All baseline laboratory data including absolute neutrophil count, absolute lymphocyte count, hemoglobin, blood albumin level, and LDH level were similar between groups. In addition, disease stage, International Prognostic Index (IPI), and age-adjusted IPI were not statistically different between the two age groups. Baseline comorbidities quantified with CIRS scoring showed that pts >70 had a higher average CIRS score (7.5 vs. 5.8, p <0.005), and a greater proportion had severe or not optimally controlled chronic baseline conditions (43% vs. 23 %, OR 2.5, p< 0.03). The two groups had a similar average number of chemotherapy cycles (5.8 vs. 5.7). The average chemotherapy dose intensity was lower in pts> 70 and experienced a greater frequency of dose reductions during treatment (73% vs. 18%, OR 12, p<0.001). The average relative dose intensity however remained greater than 70% of reference standard intensity in 32 of 37 aged patients (86%). Furthermore, only 4 of the aged patients (11%) received doxorubicin at an RDI < 10mg/m2/week. A complete response was observed in 92% of the patients and a difference was not observed between the two age groups (95% vs 91%). Frequency of neutropenia (grade 3–4) and febrile neutropenia was similar between age groups (43% vs. 45% for neutropenia, 22% vs. 17% febrile neutropenia). Prophylactic colony stimulating factors from the onset of RCHOP was more commonly administered among the elderly (92% vs. 28%, OR 29, p<0.001). Despite the use of early growth factors and dose reductions, the frequency of at least one hospitalization during chemotherapy was significantly higher among the octogenarians and nonagenarians (54% vs. 32%, OR 2.5, p<0.03). Multivariate logistic regression analysis was performed to identify age, BSA and comorbidity scoring as statistically significant predictors of any dose reduction after controlling for sex, LDH level, disease stage, performance status, and prophylactic G-CSF use. Conclusion: Our study identifies age as a predictor of dose reduction in RCHOP used to treat patients with aggressive lymphoma. The RDI of anthracycline among the vast majority of patients was maintained at greater than 10mg/m2/week and may help explain the high frequency of complete response observed in both age groups. We conclude that patients over the age of 70 years can receive an attenuated dose of chemotherapy without compromising the response rates while experiencing similar toxicities. Additional studies with expanded population size and extended outcome data could help identify target RCHOP intensity for elderly patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2988-2988 ◽  
Author(s):  
Anne Etienne ◽  
Aude Charbonnier ◽  
Thomas Prebet ◽  
Diane Coso ◽  
Evelyne D’Incan ◽  
...  

Abstract New international recommendations of response for treatment of AML include morphologic complete remission with incomplete blood count recovery (CRi). This response criteria was defined following evaluation of new drugs used for the treatment of AML in first relapse (Sievers et al., JCO2001;19:3244–3254). The objective of our study was to evaluate this criterion in elderly patients with AML who are in first line of treatment. Between 1995 and 2006, 454 patients aged 55 years or older with previously untreated acute non promyelocytic leukemia received a conventional anthracycline and cytarabine induction chemotherapy in our institution. Ages were between 55 and 85 years (median 65 years). Two hundred and fourty-eight patients achieved a complete response (CR) (55%), 37 patients achieved CRi (8%), 104 patients had persisting leukemia (23%), and 49 died during remission induction therapy (13%). Multilineage dysplasia, secondary AML and blasts expressing CD34 were significantly more frequent in patients achieving CRi than CR (58% versus 29%, p=0.001, 33% versus 15%, p=0.007, and 79% versus 54%, p=0.01, respectively). No favorable prognostic karyotype was found in the CRi group but cytogenetic distribution did not differ statistically between the two groups. All patients who reached CR or CRi were scheduled to receive consolidation. Only 24 patients (65%) in CRi actually received this consolidation chemotherapy course and 11 patients (30%) had intensification (intermediate-dose cytarabine and/or autologous stem cell transplantation) whereas for patients achieving CR, 233 (94%) and 214 patients (86%) received consolidation and intensification, respectively (p&lt;0,001 for both). None of the patients in CRi received an allogenic stem cell transplantation whereas 18 (7%) of CR patients had one (p=0,2). Disease-free survival (DFS) and remission duration were significantly different between patients in CRi and CR, with a median of 4 and 12 months, and 5 and 9 months respectively (p&lt;0,001 and 0,03). The median overall survival (OS) was also significantly lower for patients in CRi versus CR, respectively 8 and 23 months (p&lt;0,001). By landmark analysis, there was no difference in OS between patients in CRi and a group of 98 patients with induction failure surviving at least 60 days (p=0,4). We also noted that OS was better, in the group of patients in CRi, for those who finally achieved CR criteria after 1 or more course of post-remission chemotherapy (median 16 months, against 7 months for patients still in CRi, p=0,03). Our results show that the CRi criterion is not equivalent to CR in elderly patients who received intensive chemotherapy as the first line treatment of AML. This should be kept in mind when the results of new agents used in this setting are compared to historical data.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14140-e14140
Author(s):  
Christian Jehn ◽  
L. Böning ◽  
Hendrik Kröning ◽  
Kurt Possinger ◽  
Antonio Pezzutto ◽  
...  

e14140 Background: In clinical practice elderly patients (pts) with comorbidities may not be treated appropriately based on perceptions about their life expectancy and ability to tolerate potential side effects of chemotherapy. We investigated the influence of comorbidity, ECOG status and age on the efficacy and safety profile of cetuximab and irinotecan in irinotecan pretreated mCRC patients aged < 65 and > 65 years. Methods: 497 irinotecan-pretreated pts with mCRC were entered in the database of this noninterventional study. Comorbid conditions were recorded and scored according to the Charlson Comorbidity Index (CCI). Descriptive statistics, χ²-or Fishers exact test and multivariate analysis were applied. Results: A total of 247 and 250 pts aged < 65 (median:59) and > 65 (median:70) years, respectively, were documented. 79% of the pts showed a reduced ECOG status of 1–2, with no difference the age groups (p=0.65). Grade III/IV toxicities occurred in 18 % of pts without any difference between age groups although older pts had more comorbidities, with a higher CCI (p=0.002). The duration of any grade of skin reaction was in pts age < 65 significant longer (42 d), than in patients aged > 65 (31 d); (p=0.04). However, there was a trend towards higher grade (≥2) skin toxicity in pts aged > 65. A total of 71% of the pts developed skin rash, which was strongly related to response (P=0.006). Age, line of therapy, ECOG, gender, CCI had no influence on response in multiple regression analysis. The objective response rates were similar for both groups: 38.1% for age < 65 vs. 36.4% for age > 65 (p=0.57). Progression-free survival (PFS) did not differ between pts 18–65 years old (6.0 months) in comparison with pts >65 years (6.1 months) (p=0.99; log-rank test). In a multivariate analysis only ECOG status had a negative impact on PFS (HR: 0,499; 95% Cl, 0.34–0.72; p=0.002), but not CCI, age or gender. Conclusions: Only ECOG had a negative influence on PFS. There were no significant differences in response rate and safety profile for patients aged < 65 and > 65 years when treated with cetuximab and irinotecan. Comorbidities had no influence on efficacy or toxicity.


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