Choice Of First-line Chemotherapy Research Articles

Abstract PO5-04-12: Comparison of chemotherapy efficacy in metastatic lobular vs. ductal breast cancer

Abstract Comparison of chemotherapy efficacy in metastatic lobular vs. ductal breast cancer Background: Invasive lobular carcinomas (ILC) are thought to be less chemo-sensitive than invasive ductal carcinomas (IDC), as reflected by lower rates of pathological complete response following neoadjuvant therapy. In the metastatic setting, evidence regarding chemotherapy (Cx) efficacy is limited. Methods: A retrospective review of prospectively collected data for consecutive patients (pts) with metastatic ILC (mILC) treated at a single institution between 2000 and 2023 was included. Pts with mILC were matched on a 1:2 ratio with a cohort of pts with metastatic IDC (mIDC) by age, era of diagnosis and initial metastatic burden. Primary outcome was efficacy of Cx in mILC vs. mIDC pts as measured by time to next treatment - TTNTc (months (m) between start date of first & second Cx). Key secondary endpoints included differences in efficacy of endocrine therapy between the two groups (as measured by TTNT and outcomes in pts with endocrine resistance (EnR) as defined by ESMO consensus guideline) and overall survival (time from diagnosis of metastatic breast cancer (BC) to death or last follow-up [OS]). Results: 376 pts were included, mILC (122) and mIDC (254) with median age 64y and 62y, respectively. A significantly higher proportion of mILC pts had hormone receptor positive/HER2 negative or lower proportion of triple negative disease (p< 0.0001). Compared to mIDC, mILC pts were more likely to have de novo disease (29% vs. 18%; p=0.02), lower grade (p< 0.0001), received endocrine therapy only (p=0.03) and were less likely to have visceral disease at diagnosis or any time after metastatic diagnosis (20% vs. 45% p< 0.0001, 35% vs. 51% < 0.0004, respectively). Median time to commencing chemotherapy from metastatic diagnosis was longer in mILC pts (5.8 v 2.0 m, p=0.03). There was no significant differences in TTNTc for patients with mILC and mIDC except for those with visceral disease at diagnosis (Table 1). There was no significant difference in TTNTc by histological subtype of mILC (p=0.46) or by choice of first line chemotherapy used (p=0.91). In the entire population, no significant OS difference observed in mILC and mIDC (Table 1). BC outcome was assessed in pts receiving endocrine therapy as first-line treatment (mILC 65, mIDC 102). There was no difference in TTNT (mILC 14.6m vs. mIDC 14.8m). There were no differences in incidence of EnR between the groups. OS was shorter in mILC pts with primary EnR. The presence of primary, secondary or no resistance within each histological group was significantly associated with OS (Table 1). Conclusion: Pts with mILC have a longer time to commencing chemotherapy, but efficacy of chemotherapy is similar to pts with mIDC; irrespective of lobular histologic subtype, first line chemotherapy regimen used and sites of disease, except for those mILC with visceral disease. There was no significant difference in OS between mILC and mIDC pts treated in this single centre study. Efficacy of endocrine treatment when given as first line treatment was similar in both groups with no significant difference when pts were evaluated by presence or absence of endocrine resistance, except for primary EnR, but pt numbers were small in this group. Our results demonstrate equivalent chemotherapy efficacy in pts with mILC as compared to mIDC.

390P Impact of age on treatment strategies in RAS/BRAF wild-type metastatic colorectal cancer (mCRC): A prespecified subgroup analysis of the GERCOR-PRODIGE STRATEGIC-1 phase III study

Nearly half of patients (pts) with CRC are over 70 years old in clinical practice. STRATEGIC-1 compared FOLFIRI-cetuximab followed by mFOLFOX6-bevacizumab (Arm A) to OPTIMOX-bevacizumab followed by FOLFIRI-bevacizumab and EGFR monoclonal antibody +/- irinotecan (Arm B) in pts with previously untreated RAS/BRAF wild-type unresectable mCRC. To elucidate the impact of age on treatment efficacy, we evaluated duration of disease control (DDC) and overall survival (OS). A subgroup analysis of pts ≥70 years old was preplaned. Pts were divided into two age groups, <70 and ≥70 years, at the time of diagnosis. DDC and OS were expressed by the Kaplan-Meier method and compared by log-rank testing and Cox regression. In the general population (N=263), 187 pts (71%) and 76 pts (29%) were <70 and ≥70 years old, respectively. In Arm A (N=131) and in Arm B (N=132), 35 pts (27%) and 41 pts (31%) were ≥70 years old, respectively. Subgroup analysis showed that age had similar prognostic value in terms of DDC (22.0 months in younger vs 25.3 months in elderly [HR=0.91, 0.66-1.25; P=0.553]) and OS (36.5 months vs 34.9 months [HR=1.08, 0.78-1.48; P=0.648], respectively). Although OS was significantly improved in Arm A (HR=1.45, 1.02-2.08; P=0.039) in <70 pts, median OS was better in Arm B in ≥70 pts (42.1 vs 33.7 months; but statistically non-significant [P=0.161]). The effect of age on the treatment efficacy is shown in Table.Table: 390PPts <70 yearsPts ≥70 yearsArm AArm BHR (95%CI)PArm AArm BHR (95%CI)PNo.96913541DDC, median (months)22.820.91.05 (0.75-1.48)0.76422.528.90.83 (0.48-1.42)0.483OS, median (months)42.631.71.45 (1.02-2.08)0.03933.742.10.90 (0.53-1.53)0.161 Open table in a new tab These results confirm the polychemotherapy regimens efficiency associated to targeted therapies despite of the age, but elderly were underrepresented in trial compared to real life. The best choice of first-line chemotherapy in older pts remains unclear. The COLAGE GERCOR study, assessing the quality of life in elderly treated by FOLFOX-bevacizumab vs the standard first-line treatment (capecitabine-bevacizumab), and further studies are needed to better target elderly with mCRC.

Shorter duration of first-line chemotherapy reflects poorer outcomes in patients with HER2-negative advanced breast cancer: a multicenter retrospective study

Post-progression survival affects overall survival (OS) in patients with HER2-negative advanced breast cancer (HER2-ABC); thus, the optimal choice of first-line chemotherapy (1LCT) remains controversial. We investigated patients with HER2-ABC focusing on their sensitivity to 1LCT. We retrospectively analyzed patients with HER2-ABC who received 1LCT between January 2011 and December 2016 in three participating institutions. We identified 149 patients in the shorter and 152 patients in the longer time to treatment failure (TTF) groups. The median OS was significantly longer in the longer TTF group (hazard ratio [HR] 0.44, P < 0.001, log-rank). In the shorter TTF group, OS of patients who received paclitaxel plus bevacizumab (PB) therapy was significantly inferior to that of those who received chemotherapy other than PB (HR 2.57, P < 0.001, log-rank), and subsequent eribulin therapy significantly improved OS from 1LCT initiation (Wilcoxon P < 0.001); multivariate analyses showed that 1LCT PB therapy was an independent risk factor for poorer OS (HR 2.05, P = 0.003), while subsequent eribulin therapy was an independent prognostic factor for better OS (HR 0.56, P = 0.004). OS was significantly poorer in patients with HER2-ABC with a shorter duration of 1LCT, including PB therapy, while subsequent eribulin therapy improved OS.

Treatment patterns and survival outcomes of older patients with advanced pancreatic cancer (APC): A Canadian real-world evidence study.

385 Background: We aimed to compare chemotherapy regimens used and overall survival (OS) among geriatric patients (≥ 75 years) with APC as compared to old (65-74 years) and young (&lt; 65 years) patients with APC. Methods: In this retrospective population-based analysis, we identified patients with APC (defined as inoperable/metastatic disease) from 5 large provinces in Canada who were diagnosed from 2011 to 2016. Kaplan-Meier curves were plotted to derive OS and multivariable Cox regression models were constructed to determine the associations of different age groups on OS. Results: We included 636 patients diagnosed with APC of whom 258 (40.6%), 247 (38.8%) and 131 (20.6%) were young, old and geriatric. Approximately half (45.7%) of all patients were women. Eastern Cooperative Oncology Group performance status (ECOG PS) was known in 508 patients at diagnosis among whom 62.2% were 0-1 and 37.8% were 2+. ECOG PS was more likely to be 2+ in the geriatric group (46.8% vs 41.1% vs 31.3%; P = 0.017). Most patients (95.8%) had metastatic disease while the remaining patients had inoperable locally advanced disease. Within the study cohort, 38.7% received chemotherapy. Treatment rates differed based on age: 41.9% in young patients, 40.9% in old patients and 28.2% in geriatric patients (P = 0.02). Choice of first-line chemotherapy varied and included FOLFIRINOX (F) in 99 (40.2%), gemcitabine and nab-paclitaxel (GN) in 91 (37.0%) and gemcitabine (G) in 56 (22.8%). F, GN and G were administered in 27.0%, 32.4% and 40.5% of geriatric patients, 40.6%, 32.7% and 26.7% of old patients, and 44.4%, 42.6% and 13.0% of young patients, respectively (P = 0.007). After adjusting for baseline factors, both geriatric (odds ratio [OR], 0.70; 95% confidence interval [CI], 0.42-1.17; P = 0.175) and old patients were as likely to receive chemotherapy (OR, 1.04; 95% CI, 0.70-1.56; P = 0.815) as their young counterparts. The median OS was 7.1 (6.3-8.4), 6.7 (5.5-8.9) and 5.3 (4.3-6.8) months in young, old and geriatric patients, respectively. After adjusting for baseline variables, both geriatric (hazard ratio [HR], 1.25; 95% CI, 0.96-1.62; P = 0.101) and old patients (HR, 1.16; 95% CI, 0.94-1.42; P = 0.171) experienced similar OS as young patients. ECOG PS 2+ at presentation was associated with worse OS as was treatment with G. Conclusions: Overall treatment rates for APC are low in the real world. The poor OS in geriatric patients with APC is driven by poor PS and use of less intensive chemotherapy. Age alone should not be considered a contraindication for more intensive chemotherapy since treatment benefit is observed across all age groups. [Table: see text]

Treatment of metastatic recurrence of urothelial carcinoma after previous cisplatin-based chemotherapy: A retrospective comparison of different chemotherapy regimens.

e17005 Background: The optimal choice of first-line chemotherapy for urothelial carcinoma (UC) patients who recur after previous cisplatin-based chemotherapy for locally-advanced disease is unclear. Our objective is to compare the efficacy of platinum (PBC) versus non-platinum (NPBC) based first-line chemotherapy regimens for such patients after metastatic recurrence. Methods: Data was collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database consisting of patients with muscle-invasive or advanced UC from 28 centers between 2005 and 2012. Patient inclusion criteria included: 1) UC with no initial metastases (cT2-4, cN0-N3, and cM0), 3) receipt of cisplatin in the locally advanced setting, and 4) receipt of chemotherapy in the first-line metastatic setting. Overall survival (OS) was the primary endpoint. Secondary endpoints included progression-free survival (PFS) and response to chemotherapy. Kaplan-Meier and Cox regression models estimated OS, PFS, and response, adjusting for age, gender, Eastern Cooperative Oncology Group (ECOG-PS), Charlson comorbidity index (CCI), surgery, T and N stage, albumin, creatinine clearance, number of initial cisplatin cycles, and time from last chemotherapy. Results: 152 patients with metastatic UC (88 PBC and 64 NPBC) were analyzed. Twelve (7.9%) patients received local definitive radiation and 7 of these 12 also underwent cystectomy. The most common NPBC regimens included taxanes, gemcitabine, or pemetrexed. The median OS was 8.70 (95% CI: 7.53 to 11.16) and 10.27 months (95% CI: 7.37 to 13.10) for PBC and NPBC (HR: 1.04, 95% CI: .67 – 1.61, p = 0.86), respectively. Multivariable analysis showed an independent prognostic effect on OS for number of previous chemotherapy cycles (3-4 vs. 1-2) (HR: 0.44, 95% CI 0.20 – 0.96, P = 0.03) and whether surgery was performed (HR: 0.44, 95% CI 0.26 – 0.75, P = 0.003). Time from last chemotherapy was not prognostic for OS (HR: 0.99, 95% CI: 0.99 – 1.00, p = 0.19). There were no significant differences for both investigator-designated PFS (HR: 0.84, 95% CI: 0.57 – 1.24, p = .39) and response to chemotherapy between PBC and NPBC (p = 0.57). Conclusions: There is no significant outcome difference between PBC vs. NPBC in patients with metastatic-recurrent urothelial carcinoma who previously received cisplatin-based chemotherapy for locally advanced disease. Those who previously underwent radical surgery or who received 3-4 cycles of cisplatin had better OS with PBC.

Burkitt Lymphoma in Adolescents and Adults in Malawi: A Prospective Cohort Study

INTRODUCTIONBurkitt lymphoma (BL) is the most common pediatric cancer in sub-Saharan Africa (SSA), and also occurs frequently in adolescents and adults, often associated with human immunodeficiency virus (HIV). BL is highly curable in high-income countries, but outcomes are worse for children in SSA due to advanced disease and inability to achieve cytotoxic intensity comparable to high-income countries. Moreover, unlike pediatric BL, there are few high-quality prospective studies describing non-pediatric BL in SSA. METHODSWe prospectively enrolled patients with newly diagnosed BL from 2013 to 2018 in Malawi, a low-income country in SSA, and restricted analyses to patients aged ≥15 years. Diagnoses were confirmed using local performed immunohistochemistry, real-time telepathology, and subsequent secondary review in the United States. Participants received standardized treatment according to local pediatric or adult standards of care, with concurrent antiretroviral therapy (ART) if HIV+. RESULTS36 patients ≥15 years with BL were enrolled, with median age 21 years (range 15-61), and 44% being HIV+. Five (14%) participants were over 40 years of age. At diagnosis, 23 (64%) participants presented with abdominal disease, 5 (14%) had CNS disease, and 5/23 (22%) had bone marrow involvement. 25 (69%) participants had B symptoms, 27 (75%) had stage 3/4 disease, and 19 (56%) had ECOG performance status >1. Among 16 HIV+ participants, 9 (56%) were aware of their HIV diagnosis for a median of 1.4 years (range 0.4-9.4) prior to BL diagnosis, and 8 (50%) were on ART for a median of 1.1 years (range 0.4-2.6). Among all HIV+ BL patients, median CD4 count was 134 (range 29-2235), and 8 (50%) had HIV VL <400 copies/mL. Four patients (11%) died before chemotherapy initiation. First-line chemotherapy consisted of bolus anthracycline-based chemotherapy (CHOP) in 25 (78%), infusional anthracycline-based chemotherapy (EPOCH) in four (12%), and high-dose methotrexate-based chemotherapy (COPADM) in two (6%). Only one participant received rituximab with CHOP as part of a clinical trial, since rituximab is not otherwise routinely available in Malawi. Participants received a median of 4 cycles of first-line chemotherapy (range 1-8). 14/29 (48%) evaluable participants achieved a complete response, 7 (24%) had a partial response and 8 (28%) were refractory. Median overall survival (OS) was 7 months and one-year OS was 36% (95% CI 20-52%). In a multivariate Cox proportional hazards model, death was associated with stage 3/4 disease (HR 6.3 [95% CI 1.4-27.2]; p=0.01) and ECOG performance status >1 (HR 7.4 [95% CI 1.5-35.1]; p=0.01) with a trend toward worse survival in HIV+ participants (HR 5.9 [95% CI 0.9-39.4]; p=0.07). There were no clear differences in outcome observed based on choice of first-line chemotherapy. Of 23 deaths during the follow-up period, six (26%) were classified as treatment-related. CONCLUSIONSThis is one of the best characterized prospective cohorts of non-pediatric BL in SSA, which occurred primarily among adolescents and young adults. Outcomes were worse than pediatric cohorts from the region, with most deaths due to progressive BL. This study highlights the need to develop effective treatments for non-pediatric BL with and without HIV in resource-limited settings, where high-intensity strategies from high-income countries may have limited applicability. DisclosuresFedoriw:ALEXION PHARMACEUTICALS: Consultancy, Honoraria.

Chemotherapy for previously unresectable colorectal metastases: Multi-line strategies and targeted therapies

The advent of more active cytotoxic drugs (oxaliplatin, irinotecan), combined with targeted therapies and advances in surgery, has increased the survival of patients with metastatic colorectal cancer. The choice of first-line chemotherapy in case of patients with definitely non-resectable metastasis is guided by the merits and feasibility of aggressive treatment, history of prior adjuvant oxaliplatin, and tumor RAS status that has become essential. A major prognostic factor is patient’s access to all anticancer drugs, which is linearly correlated to survival. The same is probably true regarding targeted agents. The combination of doublet chemotherapy (fluoropyrimidine combined with oxaliplatin or irinotecan) and a targeted agent (bevacizumab or anti-EGFR antibodies if wild-type RAS) is the first-line standard of care for patients with non-resectable metastasis. In case of disease control after a 4–6 month induction bitherapy, treatment maintenance with a fluoropyrimidine (alone or combined with bevacizumab) until disease progression is a therapeutic option. Supplementary data are warranted to select subgroups of patients that may benefit from intermittent treatment to improve quality of life. In case of slowly growing metastatic disease and/or in frail patients, fluoropyrimidine (alone or combined with bevacizumab) may also be a first-line treatment option (oxaliplatin or irinotecan being added at the time of disease progression), without damage to survival compared with a strategy based on immediate doublet chemotherapy continued until progression or dose-limiting toxicity. On the other hand, survival rates ever achieved were obtained in selected patients after tricytotoxic-induction therapy (alone or combined with targeted agent) followed by maintenance treatment. These strategies deserve to be compared through further randomized trials.

Angioimmunoblastic T cell lymphoma: clinical analysis of 42 cases

To explore the clinical characteristics and prognosis of patients with angioimmunoblastic T cell lymphoma (AITL). The clinical features and prognostic factors of 42 cases newly diagnosed as AITL at Peking University Cancer Hospital from January 2007 to August 2012 were retrospectively analyzed. Their median age was 59(34-76) years. Among them, 97.6% cases (41/42) belonged to Ann Arbor stage III/IV, 73.8% (31/42) cases presented with B symptoms, 85.7% (36/42)cases had painless lymphadenopathy, 52.4% (22/42)cases extranodal involvement, 64.3% (27/42) cases elevated lactate dehydrogenase and 45.2% (19/42) cases elevated β2-microglobulin at diagnosis. And 40.5% (17/42) cases had 3 points of international prognostic index (IPI) score with the highest proportion.First-line chemotherapy was predominantly CHOP (cyclophosphamide, vincristine, doxorubicin, prednisolone) or CHOP-like-based and complete response was achieved in 44.7% (17/38) of them. The median follow-up time was 40 (2-106) months The 1, 2, 5-year survival rates were 78%, 57% and 39% respectively.Statistical analysis showed that IPI was an independent prognostic factor (P = 0.009).Other factors included gender (P = 0.311), age (P = 0.263), with or without B symptoms (P = 0.102), Ki-67 index (P = 0.146) as well as the choice of first-line chemotherapy (P = 0.292) each had a tendency of affecting; the survival rate, but failed to reach statistical significance. Angioimmunoblastic T-cell lymphoma is a major type of peripheral T-cell lymphoma. Most AITL patients are elders with a late stage. The disease generally displays an aggressive clinical course and poor prognosis.

Treatment center (TC) variability in survival of patients (pts) with colorectal cancer (mCRC) treated with bevacizumab (BV): A subanalysis from the BRiTE Observational Study (OCS)

e17532 Background: Treatment options and overall survival (OS) rates for pts with mCRC have increased markedly over the past decade. However, the variability in OS across TCs, and possible contributing factors (measured and unmeasured), remain unclear. We present an analysis from the BRiTE OCS assessing variability in OS as a function of TC, and sought to identify site factors that may predict better outcomes. Methods: BRiTE enrolled 1,953 pts with mCRC receiving a first-line BV-based regimen, from 248 U.S. sites, mostly community practices (Grothey et al. J Clin Oncol. 2008 26:5326). A Cox proportional hazard model was used to identify predictors of OS (age, PS, albumin, alkaline phosphatase, site of primary tumor) and calculate the expected number of deaths (E) compared to the observed number of deaths (O) within each TC. The ratio O/E was calculated and its distribution is presented. Sites with high O/E (top 25%) vs low O/E (lowest 25%) were titled “worst” (W) and “best” (B), respectively. B and W sites were compared by type (academic vs community, hospital vs clinic, urban vs rural), number of pts treated, choice of first-line chemotherapy, postprogression (PD) therapy, and duration of BV. TCs with ≥3 pts were included in the analysis (198). Results: Significant variation in the O/E ratio was observed across TCs ( Table ). The differences between W and B TCs were that pts at W TCs were less likely to receive a first-line oxali containing regimen (65% vs 67%), had shorter overall duration of BV (8 m vs 12 m) and were less likely to use BV following PD (33% vs 39%). Measured site, pt, and treatment variables explained ∼7% of the variability in O/E, suggesting most TC variability was due to unmeasured factors. Conclusions: Significant variability in OS exists across BRiTE TCs, which appears partly related to the specific therapies received by pts. Further work is needed to determine whether W TCs can be optimized and improve outcomes in pts with mCRC. [Table: see text] [Table: see text]

Phase II study of tailored chemotherapy for advanced colorectal cancer with either 5-fluouracil and leucovorin or oxaliplatin and irinotecan based on the expression of thymidylate synthase and dihydropyrimidine dehydrogenase

Background: Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are essential enzymes for 5-fluorouracil (5-FU) metabolism. In patients with advanced colorectal cancer (ACRC), retrospective studies have shown that low expression levels of TS and DPD correlated with response to 5-FU. We performed a prospective study in which the choice of first-line chemotherapy with either 5-FU or a non-5-FU containing regimen was based on TS and DPD expression.Patients and methods: Fresh-frozen samples of metastases were obtained from 58 previously untreated patients with ACRC. mRNA expression of TS and DPD was quantified using an RT–PCR assay. Patients with low tumor expression of both TS and DPD received weekly bolus 5-FU/leucovorin (LV) 500mg/m2 (group A); patients with high TS and/or DPD received 3-weekly oxaliplatin 85mg/m2 and irinotecan 200mg/m2 (group B). After progression, cross-over to the alternative regimen was attempted.Results: Of 53 eligible patients, 31 had tumors with both low TS and low DPD, and were treated in group A. A response was observed in 11 patients [35%; 95% confidence interval (CI) 19% to 54%]. Cross-over to second-line oxaliplatin/irinotecan resulted in a partial response in two out of 16 patients (13%; 95% CI 1% to 38%). In group B, four out of 22 patients responded (18%; 95% CI 5% to 40%), while no responses were observed in 12 patients after cross-over to 5-FU/LV (0%; 95% CI 0% to 28%).Conclusions: Prospective selection of 5-FU/LV chemotherapy based on low TS and DPD expression in patients with ACRC did not confirm the high response rates reported in retrospective studies. The procedure of obtaining metastatic tissue and quantitation of enzymes appeared feasible but cumbersome. Before assessing the clinical utility of a predictive marker in a randomized trial, future studies should focus on prospective validation of the assay in a large and well defined population.

Distant Recurrence in Breast Cancer: Survival expectations and first choice of chemotherapy regimen

Controversial questions in recurrent breast cancer include the magnitude of the survival benefit of combination chemotherapy and the best choice of first line chemotherapy. Data from the files of the Danish Breast Cancer Cooperative Group (DBCG) show that with current systemic treatment median survival after distant recurrence is 19 months. Since historical data from the pre-chemotherapy era indicate a median survival of 12 months, the survival benefit of standard chemotherapy appears to be around 7 months in the average patient. The DBCG trial 80-R2 is the largest randomized trial of CAF (cyclophosphamide, doxorubicin, 5-fluorouracil) versus CMF (cyclophosphamide, methotrexate, 5-fluorouracil) in recurrent breast cancer. A review of this study and 6 other similar studies shows that CAF is clearly superior to CMF in terms of better tumor shrinkage, prolonged overall time to progression, and decreased need of secondary therapy. The adverse effects of the two treatments are largely comparable, but CAF causes severe alopecia and is more expensive than CMF. On balance, the existing evidence indicates that CAF rather than CMF should be chosen as first line chemotherapy in recurrent breast cancer.