Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument

The incidence of stage I and II nonsmall cell lung cancer is likely to increase with the ageing population and introduction of screening for high-risk individuals. Optimal management requires multidisciplinary collaboration. Local treatments include surgery and radiotherapy and these are currently combined with (neo)adjuvant chemotherapy in specific cases to improve long-term outcome. Targeted therapies and immunotherapy may also become important therapeutic modalities in this patient group. For resectable disease in patients with low cardiopulmonary risk, complete surgical resection with lobectomy remains the gold standard. Minimally invasive techniques, conservative and sublobar resections are suitable for a subset of patients. Data are emerging that radiotherapy, especially stereotactic body radiation therapy, is a valid alternative in compromised patients who are high-risk candidates for surgery. Whether this is also true for good surgical candidates remains to be evaluated in randomised trials. In specific subgroups adjuvant chemotherapy has been shown to prolong survival; however, patient selection remains important. Neoadjuvant chemotherapy may yield similar results as adjuvant chemotherapy. The role of targeted therapies and immunotherapy in early stage nonsmall cell lung cancer has not yet been determined and results of randomised trials are awaited.

Download Full-text

ENGOT-en11/GOG-3053/KEYNOTE-B21: Phase 3 study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with newly diagnosed high-risk endometrial cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps5608 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS5608-TPS5608

Author(s):

Toon Van Gorp ◽

Mansoor Raza Mirza ◽

Alain Lortholary ◽

David Cibula ◽

Axel Walther ◽

...

Keyword(s):

Quality Of Life ◽

Endometrial Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Combination Therapy ◽

Stage I ◽

Newly Diagnosed ◽

Phase 3 ◽

Eortc Qlq

TPS5608 Background: Pembrolizumab, a selective humanized anti–PD-1 monoclonal antibody, has demonstrated activity in patients with previously treated mismatch repair (MMR) deficient (dMMR; 57.1% ORR as monotherapy and 63.6% ORR as combination therapy with lenvatinib) and MMR proficient (pMMR; 36.2% ORR as combination therapy with lenvatinib) endometrial cancer (EC). ENGOT-en11/GOG-3053/KEYNOTE-B21 is a phase 3, randomized, double-blind study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with EC. Methods: Eligible patients are ≥18 years old with newly diagnosed, histologically confirmed high-risk (stage I/II non-endometrioid, stage III/IVa, p53 abnormality) EC (carcinoma or carcinosarcoma) following surgery with curative intent with no evidence of disease post-operatively or on imaging, and without prior systemic therapy/radiotherapy. In total, ̃990 patients are randomized to receive pembrolizumab 200 mg or placebo Q3W for 6 cycles + chemotherapy (carboplatin area under the curve [AUC] 5 or 6 + paclitaxel 175 mg/m2 Q3W or carboplatin AUC 2 or 2.7 + paclitaxel 60 mg/m2 QW) in stage 1. Patients receive pembrolizumab 400 mg or placebo Q6W for 6 cycles in stage 2 per their treatment assignment. At the investigator’s discretion, radiotherapy (external beam radiotherapy [EBRT] and/or brachytherapy) ± radiosensitizing cisplatin 50 mg/m2 (days 1 and 29) may be administered after completion of chemotherapy. Randomization is stratified by MMR status (pMMR vs dMMR) and, within pMMR, by planned radiation therapy (cisplatin-EBRT vs EBRT vs no EBRT), histology (endometrioid vs non-endometrioid), and International Federation of Gynecology and Obstetrics (FIGO) surgical stage (I/II vs III/IVA). Dual primary endpoints are disease-free survival (DFS; per investigator assessment) and overall survival (OS), both estimated by the Kaplan-Meier method, with a stratified log-rank test to assess treatment differences and a Cox proportional hazard model with Efron’s method of tie handling to assess the magnitude of treatment differences. Secondary endpoints include DFS (per blinded independent central review), DFS (per investigator assessment) and OS by biomarker status (PD-L1 and tumor mutational burden), safety (per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) and quality of life (per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] and Endometrial Cancer Module [EORTC QLQ-EN24]). The study began enrollment in December 2020. Clinical trial information: NCT04634877.

Download Full-text

Clinical Outcome of Patients With High-Risk Endometrial Carcinoma After Treatment With Chemotherapy Only

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001356 ◽

2018 ◽

Vol 28 (9) ◽

pp. 1789-1795 ◽

Cited By ~ 4

Author(s):

Elisabeth Smogeli ◽

Milada Cvancarova ◽

Yun Wang ◽

Ben Davidson ◽

Gunnar Kristensen ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Recurrence Rate ◽

Total Population ◽

Standard Treatment ◽

International Federation ◽

Stage I ◽

Stage Ii ◽

Stage Iiic ◽

Gynecology And Obstetrics

ObjectivesAdjuvant treatment of high-risk endometrial cancer (EC) is still controversial. Several studies have tried to clarify the best treatment strategy, and guidelines have been made, but no study to date has shown a survival benefit for radiation over chemotherapy. We aimed to evaluate the outcome of high-risk EC patients treated with adjuvant chemotherapy only in a population where the routine administration of adjuvant radiotherapy was omitted.MethodsThis is a retrospective study including 230 EC patients with International Federation of Gynecology and Obstetrics stage I type II, stage Ib type I/G3, stage II, and IIIc treated at Oslo University Hospital between 2005 and 2012. Standard treatment was hysterectomy, bilateral salpingo-oophorectomy and at least pelvic lymphadenectomy followed by adjuvant chemotherapy.ResultsOf the 230 high-risk patients, standard treatment was given to 146 patients (63.5%): 60 patients in stage I, 10 patients in stage II, and 76 patients in stage IIIc. Only 10% of patients with stage I disease relapsed, with 3.3% locoregional relapses and 6.7% distant relapses. Recurrence rate in stage IIIc was 39.5%, with 7.9% isolated vaginal and 31.6% distant relapses. The 3-year disease-free survival was 92% for stage I, 80% for stage II, and 60% for stage IIIc disease. In the total population, 55 patients had International Federation of Gynecology and Obstetrics stage Ia, 43 Ib, 42 stage II, and 90 stage IIIc disease. Recurrence rate in the total population was 29.6%, with 9.6% isolated vaginal recurrences, 1.7% recurrences located in the pelvis, and 18.3% distant recurrences.ConclusionsPatients with high-risk EC have acceptable vaginal/pelvic control rates after adjuvant chemotherapy. However, prognosis remains poor for patients with stage IIIc disease, also after chemotherapy.

Download Full-text

Abstract P1-12-02: Sequential versus concurrent administration of epirubicin and docetaxel as adjuvant chemotherapy in women with high-risk axillary lymph node negative early breast cancer. An interim analysis of a multicenter randomized study from the Hellenic oncology research group

10.1158/1538-7445.sabcs15-p1-12-02 ◽

2016 ◽

Author(s):

D Mavroudis ◽

E Saloustros ◽

I Boukovinas ◽

P Papakotoulas ◽

S Kakolyris ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Interim Analysis ◽

Randomized Study ◽

Axillary Lymph ◽

Concurrent Administration ◽

Node Negative ◽

Oncology Research

Download Full-text

Outcome of patients with early ovarian cancer undergoing three courses of adjuvant chemotherapy following complete surgical staging

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200507000-00004 ◽

2005 ◽

Vol 15 (4) ◽

pp. 601-605 ◽

Cited By ~ 2

Author(s):

M. Shimada ◽

J. Kigawa ◽

Y. Kanamori ◽

H. Itamochi ◽

T. Oishi ◽

...

Keyword(s):

Ovarian Cancer ◽

Survival Rate ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Surgical Staging ◽

High Risk Patients ◽

Platinum Based Chemotherapy ◽

Early Ovarian Cancer ◽

Risk Patients ◽

Stage Ia

We conducted the present study to determine the outcome of patients with early ovarian cancer who underwent three courses of adjuvant chemotherapy after complete surgical staging. One hundred consecutive patients with stage I–II epithelial ovarian cancer who had undergone complete surgical staging and received three courses of platinum-based chemotherapy were entered in this study. Twenty-one patients were low risk, defined as stage IA–B, grade 1 and histologic types except for clear cell adenocarcinoma, and remaining 79 were high risk. All patients with stage IA or IB, whatever histologic type and histopathologic grade, were alive without disease. The 5-year survival rate was 89.4% for patients with stage IC and 76.2% for those with stage II. The 5-year survival rate for low- and high-risk patients was 100% and 89.4%, respectively. The survival rate for grade 1 was significantly better than that for grade 2 or 3. Multivariate analysis revealed that histologic grade was an independent prognostic factor in stage IC–II ovarian cancer. The outcome of patients with early ovarian cancer undergoing three courses of chemotherapy after complete surgical staging was favorable even in high-risk patients

Download Full-text

Short-course adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis: a Medical Research Council report.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.4.1106 ◽

1996 ◽

Vol 14 (4) ◽

pp. 1106-1113 ◽

Cited By ~ 238

Author(s):

M H Cullen ◽

S P Stenning ◽

M C Parkinson ◽

S D Fossa ◽

S B Kaye ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Germ Cell ◽

Medical Research ◽

Research Council ◽

Medical Research Council ◽

Germ Cell Tumors ◽

Stage I ◽

Nonseminomatous Germ Cell Tumors

PURPOSE This United Kingdom Medical Research Council (UK-MRC) study prospectively evaluated efficacy and long-term toxicity of adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis (NSGCTT). PATIENTS AND METHODS Eligible patients were those identified by the local histopathologist as having features confirmed in MRC surveillance studies to indicate an approximate 50% risk of relapse. Central histopathology review was undertaken. Chemotherapy consisted of two courses of cisplatin 100 mg/m2, bleomycin 30 mg weekly x 3, and etoposide 120 mg/m2 x 3, every 21 days (BEP). RESULTS One hundred fourteen eligible cases were enrolled. Median time of follow-up was 4 years, with 93 patients followed-up for at least 2 years. There have been two relapses, including one patient who did not have a germ cell tumor (GCT), according to the reference histopathologist. This patient is alive with active disease, the other has died. There was one death after a cerebrovascular accident during treatment. Assessment of fertility, lung function, and audiometry pretreatment and more than 9 months posttreatment indicated no clinically significant changes. A mean decrease in transfer factor coefficient (KCO) of 15% of the predicted value was noted, but no patient had symptomatic respiratory dysfunction. CONCLUSION There have been only two relapses among 114 cases of high-risk stage I NSGCTT treated with two courses of adjuvant BEP chemotherapy. The 95% confidence interval (CI) excludes a true relapse rate of more than 5%. Of 104 patients confirmed on histopathology review to have GCT, there has been only one relapse. Adjuvant chemotherapy is free from significant long-term toxicity, offering an effective alternative to surveillance or retroperitoneal lymph node dissection (RPLND) followed by surveillance, and may be preferred by some patients.

Download Full-text