Adjuvant Single Agent Research Articles

Cost-Effectiveness of Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Single-Agent Pembrolizumab for High-Risk Early-Stage Triple-Negative Breast Cancer in the United States.

The randomized phaseIII KEYNOTE-522 trial demonstrated that addition of pembrolizumab to neoadjuvant chemotherapy provided a significant improvement in event-free survival and a favorable trend in overall survival for high-risk early-stage triple-negative breast cancer (eTNBC). This analysis evaluated the cost-effectiveness of pembrolizumab in combination with chemotherapy as neoadjuvant treatment and continued as a single-agent adjuvant treatment after surgery vs. neoadjuvant chemotherapy for patients with high-risk eTNBC in the USA. The analysis was conducted from a US third-party public healthcare payer perspective. A multistate transition model was developed using efficacy and safety data from the KEYNOTE-522 trial. The model included four mutually exclusive health states: event-free, locoregional recurrence, distant metastasis, and death to simulate patients' lifetime disease course. Quality-adjusted life years (QALYs) were calculated on the basis of EuroQoL-5 Dimensions utility data collected in KEYNOTE-522. Costs for drug acquisition/administration, adverse events, disease management, and subsequent therapies were reported (2021 US dollars). Costs and outcomes were discounted at 3% annually. A series of sensitivity analyses were performed to test the robustness of the main results. In the base case scenario, pembrolizumab plus chemotherapy followed by pembrolizumab resulted in expected gains of 3.37 life years (LYs) and 2.90QALYs, and an incremental cost of $79,046 versus chemotherapy. The incremental cost per QALY gained was $27,285, which is lower than all commonly cited US willingness-to-pay thresholds. Sensitivity analyses showed the results were robust over plausible values of key model inputs and assumptions. Compared with neoadjuvant chemotherapy, pembrolizumab in combination with chemotherapy as neoadjuvant treatment and continued as a single-agent adjuvant treatment after surgery is considered a cost-effective option for high-risk eTNBC in the USA.

A phase 3, randomized, open-label study of the anti-Globo H vaccine adagloxad simolenin/obi-821 in the adjuvant treatment of high-risk, early-stage, Globo H-positive triple-negative breast cancer.

TPS611 Background: Adagloxad simolenin (A-S) is an anti-Globo H immunogen comprised of the carbohydrate tumor antigen Globo H, covalently linked to keyhole limpet hemocyanin, a carrier protein that deploys T cells to enhance the humoral response. Administration of A-S in combination with the immune adjuvant OBI-821 serves as an anti-tumor associated carbohydrate antigen vaccine intended to generate anti-Globo H humoral responses in patients with Globo H-expressing tumors. Methods: Study OBI-822-011, a phase 3 study, was initiated in 2018. Following feedback from investigators and advisors the study design was changed from a double-blind, placebo-controlled study to an open-label, standard of care (SOC) study. The revised protocol includes patients who have recovered from surgery and completed all planned neoadjuvant and/or adjuvant multiagent chemotherapy and/or radiation therapy. SOC in the A-S/OBI-821 arm is concomitant therapy of capecitabine or immune checkpoint inhibitor. In the SOC arm patients will receive SOC therapy consisting of observation alone, or adjuvant capecitabine alone, or immune checkpoint inhibitor alone. The key protocol changes included a change from open-label to standard of care, providing unblinding and reconsent guidelines for patients enrolled into the study prior to the protocol amendment, allowing concurrent adjuvant single agent chemotherapy, revising the stratification algorithm from a non-hierarchical to a hierarchical structure and aligning the stratification factors with prognostic factors more representative of the study population, revising the eligibility criteria, number and frequency of assessments to reduce patient burden, revising the interim analysis timepoints for futility, and removed an interim analysis for superiority. Study Objectives: Primary Objective: To determine the effect of A-S/OBI-821 treatment on improving IDFS in the study population. Secondary Objectives: To determine the impact of A-S/OBI-821 treatment on Overall survival (OS), Quality of life (QoL), Breast cancer-free interval (BCFI), Distant disease-free survival (DDFS) in the study population; To determine the safety and tolerability of A-S/OBI-821 in the study population. Key Exploratory Objectives: Beyond the safety, efficacy, and QoL endpoints of this trial, exploratory endpoints will evaluate the relationship between aberrant Globo H expression and baseline characteristics, including tumor pathology and immune factors. Conclusion: An estimated 668 subjects will be enrolled, treated for up to 2 years, and followed until occurrence of 187 events (invasive disease recurrence or death) or 3 years from last subject randomized. Survival follow-up is for 5 years from randomization of last subject. Clinical trial information: NCT03562637.

Immunostimulatory and anticancer effect of Reishi and Coriol extracts at the level of clinical studies and their implementation in practice

Background Mushrooms Reishi and Coriolus have been used for centuries in Asian countries to treat various diseases, mainly respiratory tract infections or pulmonary diseases, and more recently also cancers. Polysaccharides and triterpenes, which are found in these mushrooms, are their main bio-active components. Preclinical and clinical studies in humans presented their beneficial effects as immunomodulators; besides this, they possess a direct anticancer effect. In Asia, they are used after cancer treatment as single agents or in combination with chemotherapy or radiotherapy. Extracts from Coriolus have been approved for more than 30 years as an effective adjuvant addition to standard cancer treatment in Japan and China without obvious toxicity. Purpose In this review, clinical studies with Reishi and Coriolus in cancer patients and their meta-analyses are briefly summarized. Conclusion Both extracts from Reishi and Coriolus, if used in combination with standard therapy or as an adjuvant single agent, have shown benefits at immune function measures, tumor-related symptoms and performance status of cancer patients. Moreover, they have prolonged their disease-free interval and overall survival. They are well tolerated even in advanced cancer diseases and could be safely used continuously for long periods of time. Because of clinically approved efficacy and safety, they are applied mainly in some countries as a complementary therapy for various types of cancers.

A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆

Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P= 0.042) and S-1 versus SOXRT, 0.724 (P= 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P= 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

Abstract B87: Co-expression of GLUT1 and MCT4 is a poor prognostic marker and predicts response to adjuvant chemotherapy in PDAC

Abstract Background: Mutant KRAS stimulates glucose uptake and lactate production in pancreatic ductal adenocarcinoma (PDAC), contributing to metabolic pathway reprogramming and tumor progression. A prognostic effect for glucose transporter GLUT1 and lactate transporter MCT4 expression in PDAC has been demonstrated but it is not known if the expression of markers of glycolytic and lactate metabolism pathways is predictive of treatment response. We aimed to validate the prognostic and assess the predictive effects of GLUT1 and MCT4 protein levels in resectable PDAC. Methods: Immunohistochemical analysis for GLUT1 and MCT4 was performed on a tissue microarray (TMA) comprising 261 resected PDAC tumors with associated clinical outcome data. The expression of GLUT1 and MCT4 in the epithelial compartment of PDAC was quantified and patient samples were scored as low (negative and weak staining) and high (moderate and strong staining) expression groups. Univariable disease-specific survival (DSS) was assessed using the Kaplan-Meier method. Results: 70% (182) of the patients included in the TMA had high GLUT1 staining and 58% had high MCT4 staining. GLUT1high patients had reduced median DSS compared to GLUT1low patients (1.34 vs. 2.05 years, p=0.0136). Median DSS was also reduced in the MCT4high group (1.33 vs. 1.91 years in MCT4low, p=0.0153). There was a significant co-occurrence of high GLUT1 with high MCT4 expression (70%, p<0.0001). GLUT1highMCT4high patients had reduced DSS (N=124, 1.21 years, p=0.0114) compared to GLUT1lowMCT4low (N=55, 2.04 years), GLUT1lowMCT4high (N=27, 2.12 years) and GLUT1highMCT4low (N=61, 1.85 years). 31% of all patients received adjuvant single agent chemotherapy with a pyrimidine analog. Two of the combined GLUT1/MCT4 phenotypes were found to be predictive biomarkers for adjuvant chemotherapy. GLUT1lowMCT4low showed a treatment associated two year increase in median DSS (3.32 vs. 1.38 years, p=0.0020) and GLUT1highMCT4high demonstrated a treatment associated 10 month increase in median DSS (1.68 vs. 0.89 years, p=0.0071) compared to no adjuvant therapy. No significant treatment related differences were observed in either the GLUT1lowMCT4high (p=0.24) or GLUT1highMCT4low groups (p=0.95). Conclusions: GLUT1 and MCT4 expression are poor prognostic markers in PDAC and co-expression of these biomarkers enhances this effect. Neither GLUT1 nor MCT4 were found to be of predictive relevance when considered individually. Patients with low tumor GLUT1 and MCT4 expression had the best outcomes with chemotherapy with a pyrimidine analog. Hence, immunohistochemical analysis of GLUT1 and MCT4 in resected PDAC defines patient subgroups with different survival prognosis and predicted sensitivity to pyrimidine analog chemotherapy. The combined effect of GLUT1 and MCT4 expression on PDAC outcome suggests that therapeutic agents which can alter the glycolytic/lactate pathway may have potential for increasing sensitivity to treatment. Citation Format: Joanna M. Karasinska, Steve E. Kalloger, Hui-li Wong, Taixiang Wang, Daniel J. Renouf, David F. Schaeffer.{Authors}. Co-expression of GLUT1 and MCT4 is a poor prognostic marker and predicts response to adjuvant chemotherapy in PDAC. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B87.

Severe ileitis associated with capecitabine: Two case reports and review of the literature.

Capecitabine is a commonly used anticancer drug, which has been associated with adverse events, including skin and gastrointestinal symptoms, such as vomiting and diarrhea. We herein present treated two rare cases of capecitabine-associated ileitis. In one of the patients, ileitis occurred during combination chemotherapy for metastatic colon cancer, despite previous good tolerance to this drug; the other patient developed ileitis following adjuvant single-agent treatment. The first case is unlike previously reported cases, in which patients had no past exposure to capecitabine. Ileitis may be severe but reversible with early diagnosis and proper supportive treatment, and patients may resume chemotherapy following capecitabine discontinuation.

Primary Carcinoma of the Fallopian Tube: A Review of a Single Institution Experience of 8 Cases

Aims and Objectives. To evaluate the clinicopathologic features, response to cytoreductive surgery and adjuvant platinum-based chemotherapy with or without paclitaxel. Materials and Methods. A retrospective observational study of 8 women with a histopathologic diagnosis of primary fallopian tube carcinoma (PFTC) from January 2000 to February 2013. Results. 4/8 (50%) of the women were in the early stage and an intraoperative frozen section was 100% effective in identifying fallopian tube carcinoma and then a staging laparotomy was performed. All 4/8 cases in the early stage had received and responded to single agent carboplatin and all are alive without clinical, radiological, or biochemical evidence of recurrence at the end of 2 years and the longest survivor has completed 13 years. Primary optimal cytoreductive surgery was achievable in 3/4 (75%) in advanced disease. All showed response to adjuvant paclitaxel and carboplatin (T+C), but all had succumbed to the disease following recurrence with mean progression-free survival of 19 months (range 15–21 months) and mean overall survival of 27 months (range 22–36 months). Conclusion. The pivotal role played by a frozen section in diagnosing PFTC which is rare needs to be reemphasized, therefore justifying a primary staging laparotomy in an early stage. Prolonged survival observed in this group following an optimum tailored adjuvant single agent carboplatin is worth noting.

Simplified staging laparotomy in FIGO stage 1 epithelial ovarian cancer: Follow-up and outcomes in South Wales, UK

We have conducted a retrospective analysis of FIGO stage 1 ovarian cancer patients in South Wales, who underwent a simplified staging laparotomy without routine nodal sampling and peritoneal biopsies. Patient records from January 2004 to December 2010 were analysed. A total of 116 patients were included in the final analysis. Adjuvant chemotherapy was offered to patients with risk factors for relapse (grade > 1, clear cell histology, or stage > Ia); overall, 89 patients (76.7%) received adjuvant single agent carboplatin (n = 54, 46.5%) or combination chemotherapy (n = 35, 30.2%). After a median follow up of 41 months (range 12–95), 18 patients have relapsed (15.5%), of these 17 had risk factors and 16 had received adjuvant chemotherapy. Eighteen patients have died, of whom 6 of non-cancer related causes without prior relapse. 5-year overall and relapse free survival were 80%. In conclusion, in situations where there are limited resources and operating time constraints, our data suggest that a simplified staging laparotomy approach may be a reasonable compromise in apparently early stage ovarian cancer: this may result in a more aggressive use of chemotherapy, but survival outcomes seem comparable to other series.

P-0178 - Response to Neoadjuvant Chemoradiation in Rectal Cancer: Time to Consider Risk-Adapted Adjuvant Chemotherapy

Background: Randomization of clinical trial in locally advanced rectal cancer has long been based according to pre-chemotherapy clinical stage including recently published CAO/ARO/AIO-04 German trial. Pathological stage post chemoradiation seemed to better risk- stratify patients than initial clinical stage. Few studies have been published so far pertaining the relationship of pathological stage grouping post neoadjuvant therapy and long term outcomes. To further explore on this issue, we report our experience at a single institution. Methods: 196 patients between July 2001 and December 2010 with clinical T3-4 or node positive rectal cancer who received neoadjuvant radiation only (51 pts, 26%) or 5-FU based chemoradiation (145 pts, 74%) followed by curative tumor specific mesorectal excision and had adjuvant single agent fluoropyrimidine-based chemotherapy (5-FU/LV: 115 pts, 58.7%; and capecitabine: 81 pts, 41.3%) were retrospectively reviewed. Median radiation dose: 5040 cGY. Postoperatively, the 7th edition of AJCC TNM colorectal cancer staging system was used. End points include three-year disease free survival (DFS) and five-year overall survival (OS) according to clinical and pathological stages. Differences between curves were evaluated using the log-rank test. Results: Median follow up was 46 months (2.4 -130). Median age: 55 years (range 26- 89). Male: 102 (52%). Similar three year DFS has been observed for clinical stage II and III at 66.2% and 68.3%, respectively (p= 0.909). Likewise, five-year OS was equal at 84.3% and 79.8%, respectively (p = 0.466). Three year DFS according to pathologic stages were as follows: 93% in pathologic complete remission (ypCR, n = 15), 86% in stage I (ypT1-2N0, n = 38), 78% in stage II (ypT3-4N0, n = 58), 65% in stage III (ypT1-4N +, n =85), p = 0.0006. The 5-year OS rates of these respective stages were: 100%, 92%, 86%, and 72%, p = 0.005. In ypN negative patients, multivariate analysis showed that perineural invasion was the only independent prognostic factor for DFS. None of the proposed variables emerged as an independent factor for survival. Conclusion: Pathological stage grouping post neoadjuvant therapy as opposed to clinical stage correlates well with long term outcomes in locally advanced rectal cancer. Our findings justify risk-adapted adjuvant therapy in which adjuvant chemotherapy may be omitted in ypCR and adapted in ypT3-4N0 and ypN positive patients in the context of randomized clinical trials.

Freedom from progression (FFP) by adding paclitaxel (T) to doxorubicin (A) followed by CMF as adjuvant or primary systemic therapy: 10-yr results of a randomized phase III European Cooperative Trial in Operable Breast Cancer (ECTO).

537 Background: At the time the ECTO was designed in 1996, taxanes were only indicated for patients with metastatic breast cancer. However, paclitaxel and docetaxel were still to be tested in the adjuvant setting. In addition there was relatively scarce information on the comparative efficacy of neoadjuvant and adjuvant regimens. The ECTO trial was designed to evaluate the addition of paclitaxel to an anthracycline-based adjuvant regimen and to compare this combination with the same regimen given as primary systemic (neoadjuvant) therapy. Methods: A total of 1,355 women with operable breast cancer were randomized to one of three treatments: 1) surgery followed by adjuvant single agent doxorubicin (A) followed by CMF (arm A); 2) surgery followed by adjuvant paclitaxel plus doxorubicin (AT) followed by CMF (arm B); 3) AT followed by CMF followed by surgery (arm C). The two co-primary objectives were to assess the effects on freedom from progression (FFP) of: 1) the addition of paclitaxel to post-operative chemotherapy (arm B versus arm A); and 2) primary versus adjuvant chemotherapy (arm B versus arm C). Results: At 10 years, in the adjuvant setting FFP remained statistically significant in favor of AT followed by CMF (arm B, HR 0.77, P=0.045). Distant FFP was similarly improved but overall survival was not (HR 0.82, P=0.24). There was no significant difference in FFP when chemotherapy was given after surgery compared with the same regimen given before surgery (arm B vs arm C, HR 0.79, P=0.07). In the primary chemotherapy arm, patients who achieved a pathological complete remission (pCR) had improved distant FFP (P < 0.001) compared to patients who did not achieve pCR. When given as primary systemic therapy, the paclitaxel-containing regimen allowed breast-sparing surgery in a significant percentage of patients, which did not translate in an increased risk of ipsilateral breast recurrence compared to the risk observed in patients in the adjuvant arms. Conclusions: Incorporating paclitaxel into anthracycline-based adjuvant therapy resulted in a significantly improved FFP and DFFP.

Risk-adapted adjuvant chemotherapy after concomitant fluoropyrimidine-radiotherapy neoadjuvant treatment for patients with resectable cT3-4 or N+ rectal cancer

Adjuvant chemotherapy in rectal cancer is not well defined.After neoadjuvant chemoradiation and surgery, at least a short period of treatment with 5-fluorouracil is recommended, and some investigators claim a more aggressive approach, in particular, for those patients with a high risk of systemic relapse. Nevertheless, there are few studies about adjuvant combination therapy tolerance and efficacy, and no randomized trials have been conducted comparing fluoropyrimidines versus combination therapy such as folinic acid plus 5-fluorouracil plus oxaliplatin(FOLFOX), considered the standard of care in stage IIIcolon cancer. We present an institutional series of risk adapted adjuvant therapy. Sixty evaluable patients who had received treatment with neoadjuvant fluoropyrimidine radiotherapy and surgery now received adjuvant fluoropyrimidines in the case of pT0-2N0 or oxaliplatin based combination in the case of pT3-4 or N+ . Overall, 33 patients experienced downstaging to pT2-0N0 (55%) and27 patients were restaged as pT3-4 or N+ (45%) after surgery. Local recurrence rate was 5% (three patients), one local and one local plus systemic in the adjuvant single agent group and one local plus systemic in the adjuvant FOLFOX group. Systemic relapse occurred in 14 patients(23.3%), five (15%) in the single-agent group and nine(33.3%) in the FOLFOX group. Disease-free survival at 3 years for patients in the good prognostic group(pT0-2N0) and poor prognostic group (pT3-4 or N+ ) were 78.7 and 62.2%, respectively. Severe diarrhoea was more frequent with fluoropyrimidines and neutropenia, mucositis and peripheral neuropathy were more common with FOLFOX. There were no toxic deaths. A risk-adapted adjuvant therapeutic decision is feasible with an acceptable safety profile even with the use of oxaliplatin based combinations. Three-year disease-free survival compares favourably with historical controls, especially in those patients with high risk factors for relapse.Phase III controlled trials are needed.

Neoadjuvant dose-dense sequential biweekly epirubicin and cyclophosphamide followed by docetaxel and trastuzumab for HER2+ operable breast cancer

595 Background: Neoadjuvant (Neo) chemotherapy (CT) with trastuzumab (H) improves pathologic complete response (pCR) rate for HER2+ breast cancer. Dose-dense regimens improve outcome in the adjuvant setting but have not been fully evaluated as preoperative therapy. We designed this regimen to utilize full doses of active agents including docetaxel (T) and H in a novel biweekly schedule to explore efficacy and safety. Methods: Patients (pts) with biopsy proven, clinical stage IIA-IIIC, noninflammatory breast cancer were eligible. HER2+ by FISH was determined locally. CT consisted of epirubicin (E) 100 mg/m2 and cyclophosphamide (C) 600 mg/m2 Q 14 days x 4 followed by T 75 mg/m2 and H 6 mg/kg loading dose, then 4 mg/kg Q 14 days x 4, all with pegfilgrastim support. Surgery was scheduled 20–24 weeks from start after a fifth cycle of H 4mg/kg. EF was measured prior to CT, after EC, after TH and at 6, 12 and 24 months after surgery. Additional adjuvant H to complete 1 year of therapy by conventional schedule was recommended after surgery. The primary endpoint was pCR for invasive cancer in breast and lymph nodes. Results: 30 pts were enrolled at 5 centers: median age was 50.1 (range, 31–72); ethnicity African-American 14, Caucasian 14, other 2; clinical stage IIA, 14, IIB, 4, IIIA, 7, IIIB/C, 5; ER+ 18, PR+ 14; grade 3, 21 and grade 2, 8. Twenty eight pts were evaluable for pathologic response- 2 withdrew before completing treatment, 1 for toxicity. Dose delivery on schedule was >95% for all drugs. Clinical response prior to surgery was cCR 20; cPR 5; and stable 2 pts. Pathologic response: pCR 16 (57%) including 4 with residual DCIS only; 9 pPR, and 2 stable. Mean EF was 63.1 (range, 51–81) before treatment, 62.4 (49–75) after EC and 58.3 (35–74) after TH. Two pts had EF <50% during Neo, one with clinical CHF and 1 additional pt developed CHF during adjuvant single agent H. Both pts had symptomatic improvement with cessation of H. Adverse events were generally mild with 14 grade 3 AEs including 3 episodes of dyspnea and no grade 3 skin toxicity or any grade 4 toxicity noted. Conclusions: Sequential Neo dose-dense Q 14 day EC followed by Q 14 day TH yields a high pCR rate in HER2+ breast cancer with acceptable toxicity profile and no new safety signals noted. No significant financial relationships to disclose.

S41 Targeting HER2 in the adjuvant setting: Dealing with new standards and open questions

not received. S41 Targeting HER2 in the adjuvant setting: Dealing with new standards and open questions I.E. Smith1. 1Medicine, The Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom The HER2 gene is amplified and the receptor overexpressed in around 20% of women with early breast cancer, and this is associated with an adverse prognosis. Trastuzumab (Herceptin), a humanised monoclonal antibody targeted against the external domain of the HER2 receptor, has been shown to have major clinical benefit in all stages of HER2 positive breast cancer including in particular as adjuvant therapy for early disease. The 2007 St Gallen guidelines recommended that trastuzumab should be considered as standard treatment concurrently with or sequentially after chemotherapy in patients with HER2 positive disease which is IHC (immunohistochemistry) 3+ or FISH positive except in those with a primary tumour less than 1 cm and no axillary node involvement. Important unanswered questions remain however. Concurrent or sequential therapy: Three major trials (NSABPB-31; NCCTG N9831 and BCIRG006) have shown significant survival benefit with concurrent trastuzumab given with a taxane chemotherapy following anthracycline treatment. A further major trial (HERA) has shown similar survival benefit with sequential trastuzumab given after standard adjuvant chemotherapy, but another smaller trial of sequential trastuzumab (PACS004) also given after chemotherapy has failed to show benefit. Results from the N9831 trial comparing concurrent with sequential treatment are awaited. Duration of treatment: All the major trials have empirically used one year of adjuvant trastuzumab. The HERA trial is also comparing 2 v.1 year and results are awaited. A much smaller trial (FinHER) has shown similar efficacy gains with a mere 9 weeks of trastuzumab given concurrently with chemotherapy, suggesting that much shorter treatment may be as effective. The role of anthracyclines: Adjuvant trastuzumab after anthracyclines is associated with a small but significant increase in the risk of cardiotoxicity. Results from the BCIRG 006 trial suggest that a non-anthracycline regimen of docetaxel and carboplatin with trastuzumab achieves similar efficacy to anthracycline-containing regimens but without an increase in cardiotoxicity. Standardised measurement of HER2: ASCO and the College of American Pathologists recently convened an expert panel which concluded that around 20% of current HER2 testing may be inaccurate and proposed recommendations for standardised central testing in accredited laboratories with defined proficiency testing requirements. A positive HER2 result should be defined as IHC staining of 3+ (uniform intense membrane staining of greater than 30% of invasive tumour cells) or a fluorescent in situ hybridisation (FISH) result of more than 6 HER2 gene copies per nucleus or a FISH ratio of more than 2.2. ‘Low-risk’ HER2: So called low-risk T1, N0 HER2+ve breast cancers were largely excluded from the major adjuvant trastuzumab trials but data are accumulating that these have significant risk of relapse, even including <1 cm tumours. It is likely that trastuzumab with chemotherapy would also be of benefit in these circumstances; the role of adjuvant trastuzumab alone is plausible here but no direct data are available. New anti-HER2 targeted therapies: These are rapidly becoming available including lapatinib, an oral small molecule dual HER1/HER2tyrosine kinase inhibitor with significant clinical activity in metastatic breast cancer after trastuzumab. Adjuvant single agent lapatinib is being assessed in patients with trastuzumab-naive HER2 positive breast cancer in continuing remission following adjuvant chemotherapy in the TEACH trial. In addition, adjuvant lapatinib and chemotherapy is being compared directly with trastuzumab, or the 2 agents sequentially, or in combination, in the ALTTO trial. S42 Adjuvant therapy of triple negative breast cancer E.A. Perez. Jacksonville, USA Abstract not received.not received. S43 Review of new targeted drugs: Crawling towards the adjuvant

Multicenter Study Evaluating a Dual Policy of Postorchiectomy Surveillance and Selective Adjuvant Single-Agent Carboplatin for Patients With Clinical Stage I Seminoma

No AccessJournal of UrologyUrological Survey: ABSTRACTS: UROLOGICAL ONCOLOGY: TESTIS CANCER AND ADVANCES IN ONCOLOGICAL THERAPY1 Sep 2004Multicenter Study Evaluating a Dual Policy of Postorchiectomy Surveillance and Selective Adjuvant Single-Agent Carboplatin for Patients With Clinical Stage I Seminoma Jerome P. RichieM.D. Jerome P. RichieJerome P. Richie More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)61609-6AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Multicenter Study Evaluating a Dual Policy of Postorchiectomy Surveillance and Selective Adjuvant Single-Agent Carboplatin for Patients With Clinical Stage I Seminoma." The Journal of Urology, 172(3), pp. 1203–1204 © 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 172Issue 3September 2004Page: 1203-1204 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.MetricsAuthor Information Jerome P. Richie More articles by this author Expand All Advertisement PDF DownloadLoading ...

Safety and Efficacy of Adjuvant Single-Agent Ifosfamide in Uterine Sarcoma

Purpose. The role of adjuvant therapy for completely resected uterine sarcoma continues to be debated. Previous chemotherapy trials have shown little, if any, advantage over surgery alone, with significant added toxicity. To our knowledge, the current study is the first to evaluate adjuvant ifosfamide in completely resected uterine sarcomas.Methods. Between 1992 and 1999, 13 consecutive patients with completely resected moderate- to high-grade uterine sarcoma received three cycles of adjuvant ifosfamide (1.5 g/m2/day × 3 days, repeated every 28 days). Mesna was given 30 min prior to infusion. Postinfusion mesna was administered to 10 of the patients in the outpatient setting utilizing a subcutaneous infusion pump. The remaining 3 patients received traditional intravenous mesna at 4 and 8 h after infusion.Results. The median follow-up of the patient population was 26 months. For early-stage patients (n = 10), the 2-year progression-free survival was 60%, with a median of 26 months. The 2-year overall survival was 100%, dropping to 67% at 3 years. Early-stage patients showed an advantage in both progression-free and overall survival. Early-stage patients with mixed müllerian tumor (MMT) had a significantly longer time to progression that those with leiomyosarcoma (LMS) (2-year progression-free survival of 100% versus 33%; P = 0.019). Three patients required dose reduction secondary to grade 2–3 toxicities (neutropenia ×2, nausea and vomiting ×1). All significant toxicity was eliminated with dose reduction.Conclusions. Adjuvant ifosfamide appears to be safe and well tolerated in patients with completely resected uterine sarcoma. It can easily be given in the outpatient setting if mesna is administered via a subcutaneous pump. Our data, consistent with previous studies in advanced sarcoma, suggest a potentially greater role for ifosfamide in MMT than in LMS.

Adjuvant single agent Carboplatin-therapy for clinical stage I seminoma. An alternative treatment-option?

Adjuvant single agent Carboplatin-therapy for clinical stage I seminoma. An alternative treatment-option?

Pilot studies of 2 and 1 course carboplatin as adjuvant for stage I seminoma: Should it be tested in a randomized trial against radiotherapy?

Purpose : Underpinned by increased confidence in cure of metastatic seminoma by chemotherapy during the past 12 years, three management strategies for Stage I seminoma have been evaluated by six collaborating centers within the Anglian Germ Cell Tumor Group. This paper evaluates the efficacy of surveillance, prophylactic radiotherapy and adjuvant chemotherapy, and discusses these differing management approaches. Methods and Materials : Patients were recruited into the study between 1982 and 1992. There was no randomization between treatment groups. Seventy-nine patients received prophylactic radiotherapy (median follow-up = 51 months), 67 patients had surveillance alone (median follow-up = 61 months) and 78 patients were treated with adjuvant single agent platinum (median follow-up = 44 months). Fifty-three of these patients received two courses of platinum (median follow-up = 51 months) and 25 patients received one course (median follow-up = 29 months, range 22–72 months). Results : There were 18 (27%) recurrences on surveillance, five (6%) after radiotherapy, one (1%) after two courses of adjuvant single agent platinum and none after one course of carboplatin. There was one death from testis cancer after radiotherapy and none after adjuvant chemotherapy treatments. Two patients died with drug resistant disease after relapse on surveillance. There was one death from a myocardial infarction after prophylactic radiotherapy and one death from suicide in the surveillance group. A retrospective quality of life questionnaire reviewing the incidence of early and late toxicity revealed no major differences though they suggest that those treated with one course adjuvant carboplatin had somewhat less sickness and an earlier return to work. Conclusion : Single agent carboplatin appears well tolerated and is an effective adjuvant treatment for Stage I seminoma. A multicenter randomized trial of the different treatment modalities is required to further evaluate its use.

The role of chemotherapy in the treatment of Wilms' tumor

The records of one hundred seventy-six patients with Wilm's tumor treated with transabdominal nephrectomy only or transabdominal nephrectomy, post-operative radiation therapy and several chemotherapy programs were reviewed. Three conclusions were reached: 1) The addition of postoperative radiation therapy and adjuvant chemotherapy has not improved the excellent, disease-free survival of patients with Stage I disease who were less than twenty-four months of age at diagnosis; 2) The addition of postoperative radiation therapy and adjuvant single agent chemotherapy has not improved the disease-free survival of patients with Stage II disease who were over twelve months of age at diagnosis; and 3) The use of combination chemotherapy with vincristine and actinomycin D has improved the disease-free survival of patients who present with Stage II disease.