NEWS OF THE 2019 ASCO ANNUAL MEETING: PART I

The American Society of Clinical Oncology (ASCO) Annual Meeting took place at the beginning of June in Chicago, USA. Over 40 thousand oncologists from all over the world participated in the meeting. This is one of the most important events in oncology worldwide, where the latest scientific advances are announced and discussed. Alexey Rumyantsev, MD in the Department of Clinical Pharmacology and Chemotherapy of the N.N. Blokhin National Medical Research Center of Oncology, RakFond’s grantee, IDEA (International Development and Education Award) awardee and this year’s presenter at the ASCO meeting, has put together the main news of the meeting. Part I includes studies in oncogynecology and breast cancer.

Oncogynecology

EWOC-1: choice of chemotherapy in elderly patients with advanced ovarian cancer

Aim of the study: to compare the efficacy of different chemotherapy regimens for the treatment of stage III-IV ovarian cancer in patients over 70 years old.

Study design: multi-center randomized phase III trial to evaluate the efficacy and tolerability of the three chemotherapy regimens (stratification by the outcome of the cytoreduction and by the country where a patient received the treatment):

  • Paclitaxel 175 mg/m2 + carboplatin AUC5-6 once every 21 days;
  • Carboplatin AUC5-6 once every 21 days;
  • Paclitaxel 60 mg/m2 on days 1, 8, 15 + carboplatin AUC2 weekly every 28 days.

All patients received up to 6 cycles of therapy. For patients’ selection, the GVS (geriatric vulnerability score) was used.

Results: enrollment was prematurely closed due to the revealed clear superiority of the regimens. One-hundred and twenty patients were included, patients’ characteristics were well balanced between the regimens. Median overall survival was not reached in the standard chemotherapy arm, 7.4 months in carboplatin arm (hazard ratio, HR 2.79; p < 0.001), and 17.3 months in a weekly treatment arm (HR 1.6; p = 0.123) – it means that administration of standard chemotherapy regimen leads to a significantly better survival outcome in patients.

Why it is important: it is well-known that elderly patients are less tolerant to chemotherapy, and their participation in clinical trials of anticancer drugs is limited. This is the first randomized study, which demonstrated that the standard regimen of chemotherapy should be used for treating elderly patients, rather than the use of reduced regimens due to excess toxicity risks. It is more effective.

Detailed study results:

Falandry C, Savoye AM, Stefani L et al. EWOC-1: A randomized trial to evaluate the feasibility of three different first-line chemotherapy regimens for vulnerable elderly women with ovarian cancer (OC): A GCIG-ENGOT-GINECO study. https://meetinglibrary.asco.org/record/174423/abstract.

Treatment of the carcinosarcoma of the uterus: randomized phase III trial GOG-0261

Aim of the study: to prove non-inferiority of paclitaxel/ifosfamide and paclitaxel/carboplatin in the treatment of carcinosarcoma of the uterus.

Study design: multi-center randomized phase III trial to evaluate the efficacy of the two chemotherapy regimens for carcinosarcoma of the uterus:

  • Paclitaxel 175 mg/m2 + carboplatin AUC6 – every 21 day;
  • Paclitaxel 135 mg/m2 on day 1 + ifosfamid 1.6 g/m2 on days 1, 2, 3 (+ mesna, G-CSF) – every 21 day; dose escalation was allowed.

Results: 449 patients were eligible; patients’ characteristics were well balanced between the arms. Median overall survival was 37.0 months in paclitaxel/carboplatin arm, compared to 29.0 months (HR 0.87; p < 0,01 for non-inferiority). Significant reduction in the risk of severe adverse events was found in the paclitaxel/carboplatin arm. Moreover, a significant increase of progression-free survival was observed in this arm (HR 0.735; p < 0.01 for superiority).

Why it is important: carcinosarcoma of the uterus is a rare malignant tumor, that complicates the treatment of patients with this diagnosis. The authors of this study have accomplished tremendous work and were able to prove that paclitaxel and platinum-containing regimen should be the method of choice for the treatment of carcinosarcoma.

Detailed study results:

Powell MA, Filiaci VL, Hensley ML et al. A randomized phase 3 trial of paclitaxel (P) plus carboplatin (C) versus paclitaxel plus ifosfamide (I) in chemotherapy-naive patients with stage I-IV, persistent or recurrent carcinosarcoma of the uterus or ovary: An NRG oncology trial. https://meetinglibrary.asco.org/record/173464/abstract.

Randomized SOLO-3 trial: olaparib vs. chemotherapy for platinum-sensitive relapsed ovarian cancer

Aim of the study: to compare the efficacy of olaparib and non-platinum-containing monochemotherapy in the treatment of platinum-sensitive relapsed BRCA-mutated ovarian cancer.

Study design: randomized multi-center phase III trial. Patients with BRCA-mutated ovarian cancer, who relapsed within ≥6 months after platinum-containing chemotherapy and received prior >2 lines of systemic treatment, were eligible. Randomization at 2:1 ratio to the arm of olaparib 300 mg BID, or to the arm of chemotherapy based on physician’s choice (monotherapy with paclitaxel, liposomal doxorubicin, topotecan, or gemcitabine – all drugs in standard doses). Treatment was continued until progression or intolerable toxicity.

Results: demographic characteristics were balanced between the arms. The objective response rate was 72% in the olaparib arm compared to 51% in the standard chemotherapy arm (HR 2.53; p = 0.002), median progression-free survival was 13.4 months and 9.2 months, respectively.

Comment: these results demonstrate higher efficacy of olaparib compared to chemotherapy in the treatment of relapsed ovarian cancer, however, a huge disadvantage of this work captures the attention: inadequate choice of chemotherapy for the study’s control arm – patients received non-platinum-containing monochemotherapy, that is unacceptable in the treatment of platinum-sensitive relapsed ovarian cancer. It makes the results of the SOLO3 trial irrelevant for clinical practice.

Detailed study results:

Penson RT, Villalobos RV, Cibula D et al. Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial. https://meetinglibrary.asco.org/record/173435.

Breast Cancer

MONALEESA-7: adding ribociclib to the standard first-line endocrine therapy increases the survival of patients with metastatic breast cancer

Aim of the study: to study the efficacy of adding CDK 4/6 inhibitor ribociclib to the standard endocrine therapy of metastatic breast cancer.

Study design: randomized multi-center phase III trial to evaluate the efficacy of ribociclib in addition to aromatase inhibitors compared to aromatase inhibitors alone in premenopausal or postmenopausal patients. Patients in premenopause underwent obligatory “turning off” of the ovaries.

Results: 672 patients were enrolled. Median overall survival was not reached in the ribociclib group and was 40.9 months in the standard therapy group (HR 0.71; p < 0,001). Tolerability of ribociclib was satisfactory.

Why it is important: the results of the MONALEESA-7 study demonstrated that early administration of CDK4/6 inhibitors allows patients with metastatic breast cancer live longer, which is the most important goal of the treatment of cancer patients.

Detailed study results:

Hurvitz S, Im SA, Lu YS et al. Phase III MONALEESA-7 trial of premenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy ± ribociclib: Overall survival (OS) results. https://meetinglibrary.asco.org/record/174827.

IMpassion130: atezolizumab improves overall survival in metadtatic triple-negative breast cancer

Aim of the study: to evaluate the efficacy of atezolizumab in the first-line treatment of metastatic breast cancer.

Study design: randomized placebo-controlled phase III trial to study the efficacy of adding the immunotherapeutic agent atezolizumab (anti-PD-L1 monoclonal antibody) to the standard treatment with nab-paclitaxel in patients with metastatic triple-negative breast cancer.

Results: 902 patients were enrolled; patients’ characteristics were well balanced between the arms. Median overall survival was 21.0 months in the atezolizumab/nab-palitaxel group, compared to 18.7 months in the group of nab-paclitaxel alone (HR 0.86; p = 0,07). Among PD-L1 positive patients, the median overall survival was 25.0 months and 18.0 months, respectively (HR 0.71).

Why it is important: though formally the trial was negative, a significant increase of overall survival was demonstrated in patients with PD-L1+ tumors. Triple-negative breast cancer is extremely hard to treat at advanced stages.

Detailed study results:

Schmid P, Adams S, Rugo HS et al. IMpassion130: updated overall survival (OS) from a global, randomized, double-blind, placebo-controlled, Phase III study of atezolizumab (atezo) + nab-paclitaxel (nP) in previously untreated locally advanced or metastatic triple-negative breast cancer (mTNBC). https://meetinglibrary.asco.org/record/170934/abstract

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