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Highlights

ESMO 2019: The most important take-home messages from Barcelona

Ranging from encouraging to practice-changing, these are the highlights of key opinion leaders that we interviewed during the 2019 congress.

CNS Tumors

  • A phase 0 trial in meningioma patients revealed that the CDK4/6 inhibitor ribociclib passes the blood-tumor-barrier, influences expression of proteins in the CDK signaling pathway, and leads to encouraging responses in 4 out of 8 patients (Sanai N et al. #392O).
  • A study in patients with hypermutation gliomas showed that also patients with increased inflammation in the tumor do not respond to immunotherapy (Kamiya-Matsuoka C et al. #393O).
Interview

Ass.-Prof. PD. Dr. Anna Berghoff,
Leiterin Translational Research Unit,
Klinische Abteilung für Onkologie, Universitätsklinik für Innere Medizin I, Wien

Breast cancer

  • MONALEESA 3 showed that addition of the CDK4/6 inhibitor ribociclib to fulvestrant in postmenopausal patients with hormone receptor (HR) positive, HER2 negative breast cancer improved median overall survival (mOS) compared to endocrine therapy alone in first or second line (mOS: not reached vs. 40.0 months; HR 0.724; p=0.00455; Slamon DJ et al. LBA7_PR).
  • MONARCH-2 showed superiority in overall survival (OS) with abemaciclib plus fulvestrant over fulvestrant alone in HR positive HER2 negative advanced endocrine resistant breast cancer in pre-, peri- and postmenopausal women (mOS 46.7 vs. 37.3 months; HR 0.757; p=0.0137; Sledge GW et al. LBA6_PR).
  • A phase III trial showed improvement of progression-free survival (PFS) in advanced or metastatic HER2 negative breast cancer and genomic BRCA mutations with additional treatment with the PARP1/2 inhibitor veliparib compared to chemotherapy alone (14.5 vs. 12.6 months; HR 0.71; p=0.002; Dieras V et al. #LBA9).
  • The randomized phase II trial monarcHer revealed a PFS benefit in patients with HR positive HER2 positive advanced breast cancer that were treated with abemaciclib and fulvestrant compared to trastuzumab plus standard-of-care chemotherapy (Schmid P et al. LBA8_PR).
  • Results of the KEYNOTE-522 trial show that addition of pembrolizumab to neoadjuvant and adjuvant chemotherapy for early triple-negative breast cancer increases pathologic complete response (pCR) rates (51.2% vs. 64.8%; p=0.00055). A benefit was seen also for PD-L1 negative patients (Schmid P et al. LBA8_PR).
  • The KEYNOTE-119 trial shows that pembrolizumab monotherapy did not significantly improve OS of patients with previously treated metastatic triple-negative breast cancer compared to single-agent chemotherapy. A trend in favor of pembrolizumab was seen for PD-L1 positive patients (Cortés J et al. #LBA21).

 

Interview

OA Dr. Christoph Suppan,
Med Uni Graz

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KEYNOTE-522-Studie

Daten zeigen: Pembrolizumab als Begleittherapie beim frühen triple-negativen Mammakarzinom erhöht die Chance auf eine pathologische Komplettremission.

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Colorectal cancer

  • The FoxTROT trial showed that neoadjuvant chemotherapy in patients with stage T3-4 N0-2 M0 colon cancer improved pathological downstaging including some pCRs, but not recurrence/residual disease-free survival. A subgroup of patients with KRAS mutations treated with neoadjuvant panitumumab lacked any benefit (Morton D et al #523O).
  • The phase III trial IDEA-FRANCE revealed that circulating tumor DNA analysis post-surgery detects minimal residual disease and predicts recurrence in patients with stage II or III colon cancer, and predicts optimal duration of adjuvant therapy with either three or six months of FOLFOX therapy (Taieb J et al.
    #LBA30_PR).
  • Another study showed that circulating tumor DNA detects minimal residual disease in patients with localized colorectal cancer, and identifies patients with high risk of recurrence regardless of stage, lack of CDX2 expression, and CMS subtype (Tarazona Llavero N et al. #522O).
  • In patients with initially unresectable RAS mutant colorectal liver-limited metastases, bevacizumab combined with chemotherapy improved the resectability of liver metastases and improved response rates and survival compared with chemotherapy alone (Xu J et al. #LBA31).
  • The phase II studies TRIUMPH and MOUNTAINEER demonstrate promising activity for combination of trastuzumab and another EGFR inhibitor such as pertuzumab (TRIUMPH) or tucatinib (MOUNTAINEER) in treatment-refractory metastatic colorectal cancer patients with HER2 amplifications and RASwt status (TRIUMPH: Nakamura Y et al. #526PD, MOUNTAINEER: Strickler JH et al. #527PD).
Interview

OÄ Dr. Angela Djanani,
Med Uni Innsbruck,
Leiterin der Arbeitsgruppe Gastrointestinale Onkologie der ÖGGH

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Interview

Assoz.-Prof. PD Dr. Gerald Prager,
Universitätsklinik für Innere Medizin I, MedUni Wien

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Gastric cancer and carcinomas of the esophagus and gastro-esophageal junction

  • An update of the ANGEL study showed that patients with advanced or metastatic gastric cancer who failed ≥2 prior chemotherapies benefitted from  addition of apatinib compared to best supportive care (PFS 2,83 vs. 1,77 Monate; HR 0,57; 95%-KI 0,46–0,79; p<0,0001; Kang YK et al. #LBA43).
  • The ATTRACTION-3 trial demonstrated superior OS (10.9 vs. 8.4 months; HR 0.77; p=0,02) versus chemotherapy in patients with previously treated advanced esophageal squamous cell carcinoma, with survival benefit observed regardless of tumor PD-L1 expression. The study population consisted mostly of Asian patients, only 4 per cent were Caucasian (Byoung CC et al. #LBA11).
  • The PRODIGY trial showed in Asian patients with stage 3 resectable advanced gastric cancer that neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 (DOS) led to significant tumor downstaging and improved PFS (Kang YK et al #LBA41).
  • The RESOLVE trial demonstrated, also in Asian patients with locally advanced gastric adenocarcinoma with gastrectomy, a benefit of perioperative chemotherapy of oxaliplatin combined with S-1 (SOX) versus postoperative chemotherapy of SOX or oxaliplatin with capecitabine (XELOX; Ji J et al. #LBA42).
  • In an update of the KEYNOTE-062 trial of pembrolizumab with or without chemotherapy versus chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction (G/GEJ) cancer, pembrolizumab was non-inferior to chemotherapy regarding OS, and had a more favorable safety profile. Patients with Microsatellite Instability-High (MSI-H) status achieved superior OS compared to chemotherapy (nicht erreicht vs. 8,5 Monate; HR 0,29; 95%-KI 0,11–0,81, Shitara K et al. #LBA44)
  • Another update of the KEYNOTE-062 trial showed that in patients with a Combined Positive Score ≥1 for PD-L1 expression, there was no difference in health-related quality of life measured by EORTC QLQ-C30 and EORTC QLQ-STO22 between pembrolizumab and chemotherapy (Van Cutsem E et al. #LBA45).
  • In the KEYNOTE-181 trial, the subgroup of Chinese patients with advanced/metastatic adenocarcinoma (AC) or squamous cell carcinoma (SCC) of the esophagus showed improved OS with pembrolizumab versus chemotherapy as second-line therapy (OS 8,4 vs. 5,6 Monate; HR 0,55; 95%-KI 0,36–0,82; Chen J et al. #760P)
  • In a phase II trial, combined immunotherapy and antibody-based first-line therapy with pembrolizumab and trastuzumab, followed by chemotherapy in HER2-positive metastatic esophagogastric adenocarcinoma showed promising efficacy (Janjigian Y et al. #817P).
Interview

Priv.-Doz. Dr. Aysegül Ilhan-Mutlu,
Universitätsklinik für Innere Medizin I, Wien

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Interview

Ass.-Prof. Priv.-Doz. Dr. Gerald Prager,
Universitätsklinik für Innere Medizin I, MedUni Wien

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Gynecological tumors

  • In the PRIMA trial, niraparib significantly improved PFS in patients with newly diagnosed advanced ovarian cancer, including patients at high risk of progressive disease in the HRD positive subgroup (21.9 vs. 10.4 months; HR 0.43; p<0.0001) and overall population (mPFS 13.8 vs. 8.2 months; HR 0.62; p < 0,0001; González Martín A et al. #LBA1)
  • In the PAOLA-1/ENGOT-ov25 trial, addition of olaparib to bevacizumab maintenance therapy following first-line platinum-based chemotherapy plus bevacizumab led to a statistically significant PFS benefit in patients with advanced ovarian cancer (mPFS 22.1 vs. 16.6 months; HR 0.59; 95% CI 0.49–0.72; p<0,0001;
    Ray-Coquard I et al. #LBA2_PR).
  • The VELIA trial showed that veliparib added to front-line chemotherapy and continued as monotherapy maintenance significantly extended PFS in all women with newly diagnosed high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin without selection according to BRCA mutation or HRD status, or response to chemotherapy (Coleman R et al. #LBA3).
  • An update of the phase II trial MEDIOLA revealed that around 80 per cent of patients with germline-mutated platin-sensitive relapsed ovarian cancer responded to combined therapy with olaparib and durvalumab (Drew Y et al. #1190PD).
  • In a phase Ib/II trial around 40 per cent of patients with relapsed endometrial cancer responded to combined therapy with lenvatinib and pembrolizumab regardless of microsatellite instability or mismatch-repair deficient status (Makker V et al. #994O).
Interview

Univ.-Prof. Dr. Christian Marth,
Leiter der Universitätsklinik für Frauenheilkunde, Innsbruck

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PAOLA-1/ENGOT-ov25-Studie

Erste Ergebnisse zeigen einen PFS-Benefit durch Intensivierung der Bevacizumab-Erhaltungstherapie mit Olaparib bei Patientinnen mit und ohne BRCA-Mutationen.

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Head and neck cancer

  • A Chinese phase III trial showed significantly improved OS, PFS, and ORR in primary metastatic nasopharyngeal carcinoma with addition of locoregional radiotherapy to 5-FU or cisplatin based chemotherapy (Chen M et al. #1108O).
  • In the ELAN-FIT/-UNFIT trial, patients ≥70 years with first-line recurrent and/or metastatic head and neck squamous cell cancer (HNSCC) were classified as fit or unfit using the ELAN geriatric evaluation. Fit patients benefitted from carboplatin-based EXTREME regimen, with promising overall survival (OS) which compares favorably with that of younger patients within the EXTREME trial. Unfit elderly patients were treated either with cetuximab or methotrexate. PS ECOG 2 patients did not benefit from systemic treatment (Juigay J et al. #1110O).
  • A phase II GORTEC study compared concurrent high-dose cisplatin chemoradiation plus the proapoptotic XIAP inhibitor Debio 1143 or placebo in high-risk patients with locally advanced HNSCC. Local control rate and PFS were significantly improved when Debio 1143 was added to standard chemoradiation in high-risk HNSCC patients, most of which consumed alcohol and were heavy smokers. Debio 1143 addition was feasible, safe, and did not compromise backbone therapy (Bourhis J et al. #LBA65).
  • In a substudy of a phase II EORTC umbrella trial, UPSTREAM, monotherapy with the immune modulator monalizumab was tested in patients with recurrent or metastatic HNSCC. The substudy revealed no objective response and high disease progression rates, and was closed at interim for futility, in spite of previous studies that showed efficacy of monalizumab in combination with Cetuximab in head and neck cancers (Galot R et al. #1109O).
Interview

Assoz.-Prof. PD Dr. Thorsten Füreder,
Universitätsklinik für Innere Medizin, Wien

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Hepatocellular carcinoma

  • The CheckMate 459 trial compared nivolumab or sorafenib as first-line treatment in patients with advanced hepatocellular carcinoma. Its primary endpoint of OS did not achieve statistical significance versus sorafenib (16.4 vs. 14.7 months; HR 0.85; p=0.0752; Yau T et al. #LBA38_PR), further subgroup analyses need to be awaited to determine the
    patient group with a likely benefit from nivolumab.
CheckMate 459 trial

Data from the CheckMate 459 study show a trend towards clinically meaningful improvements in survival and response rates, as well as a favorable safety profile with first-line immunotherapy compared to current standard treatment for advanced hepatocellular carcinoma.

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Lung cancer

  • In an update of the CheckMate 227 trial, chemo-free first-line therapy with nivolumab plus low-dose ipilimumab significantly improved OS versus platinum-doublet chemotherapy (17.1 vs. 14.9 months; HR 0.79; p=0.007) in patients with advanced non-small cell lung cancer (Peters S et al. #LBA4_PR).
  • The final analysis of the FLAURA trial revealed that osimertinib improved OS versus the comparator EGFR-TKIs gefitinib or erlotinib as first-line treatment for EGFR-mutated advanced NSCLC (38.6 vs. 31.8 months; HR 0.799; p=0.0462; Ramalingam SS et al. #LBA5_PR).
  • The IMpower-110 trial demonstrated superiority of atezolizumab versus platinum-based chemotherapy as first-line treatment in PD-L1–selected metastatic NSCLC, with an OS of 20.2 versus 13.1 months (HR 0.595; p=0.0106; Spigel D et al. #LBA78)
  • The phase II/III BFAST trial showed that blood-based detection via liquid biopsy can reliably identify ALK fusions, and treatment of this patient group with alectinib results in similar outcomes as in prior clinical studies (Gadgeel S et al. #LBA81_PR).
  • The first randomized trial evaluating the efficacy of immunotherapy in malignant pleural mesothelioma, PROMISE-meso, showed no improvements of PFS and OS with pembrolizumab compared to single agent chemotherapy in patients with advanced disease who progressed after or on previous platinum-based chemotherapy (Popat S et al. #LBA91_PR).
  • The NICOLAS phase II trial found that concurrent addition of nivolumab to a first-line, concurrent chemo-radiotherapy regimen in unresectable locally advanced NSCLC is safe and shows encouraging PFS and OS results (Peters S et al. #1457PD).
Interview

OA Dr. Georg Pall,
Universitätsklinik für Innere Medizin V, Innsbruck

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Interview

OA Dr. Georg Pall,
Universitätsklinik für Innere Medizin V, Innsbruck

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Breakfast Brief

Prof. Solange Peters, MD, PhD, CHUV Lausanne, puts the research she presented at ESMO 2019 in perspective by explaining the complex CheckMate 227 trial and giving an update on the NICOLAS trial.

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Melanoma

  • The 2-year results of a phase II randomized trial showed encouraging improvements in relapse-free and overall survival with neoadjuvant treatment using talimogene laherparepvec (T-VEC) in patients with resectable stage IIIB-IVM1a melanoma (Dummer R et al. #LBA66)
  • The IMMUNED trial showed that adjuvant immunotherapy with combined ipilimumab and nivolumab was superior to nivolumab monotherapy in patients with stage IV melanoma with no evidence of disease (Schadendorf D et al. #LBA67).
  • The 3-year follow up of the CheckMate 238 trial revealed superior efficacy of adjuvant nivolumab (3 mg/kg) versus ipilimumab (10 mg/kg) in resected stage III/IV melanoma (Weber J et al. #1310O).
  • The 5-year follow up of the CheckMate 067 trial showed that 53 per cent of patients with resectable stage IV melanoma treated with the combination nivolumab and ipilimumab were still alive after 5 years, most of them disease- and treatment-free (Larkin JMG et al. LBA68_PR).
  • An update of the ABC study demonstrated that patients with symptomatic brain metastases achieved improved relapse-free survival with the combination nivolumab and ipilimumab versus nivolumab monotherapy (Long G et al. #1311O).
  • The IMspire170 trial revealed that the combination of cobimetinib and atezolizumab did not result in benefit compared to pembrolizumab as first-line therapy in patients with advanced BRAFV600wt melanomas (Arance A et al. #LBA69).
Scientific knowledge exchange

Prof. Reinhard Dummer, MD, University Hospital Zurich, and Prof. Olivier Michielin, MD, PhD, CHUV Lausanne, discuss the current advances and challenges in melanoma treatment with a focus on immunotherapy.

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Renal Cell Carcinoma (RCC)

  • In the SORCE trial, no benefit could be demonstrated for adjuvant sorafenib treatment in patients with RCC at intermediate or high risk of relapse (Eisen TQ et al. #LBA56).
  • The phase II trial ENTRATA showed encouraging PFS results for addition of the glutaminase inhibitor Telaglenastat to Everolimus in patients with advanced or metastatic RCC and ≥2 prior lines of systemic therapy (Lee CH et al. #LBA54).
  • The TITAN-RCC trial revealed that in patients with advanced RCC with up to one prior line of therapy with a TKI, a tailored boost with ipilimumab can improve ORR of immunotherapy around 10 per cent in patients lacking a response, or with stable disease after nivolumab therapy (Grimm MO et al. #LBA57).
  • A phase I/II trial shows encouraging PFS in advanced RCC with the chemokine receptor (CXCR4) inhibitor X4P-001 in combination with axitinib (McDermott DF et al. #1186PD).
  • An interim analysis of a phase II trial showed that the multikinase inhibitor lenvatinib in combination with pembrolizumab can increase PFS of patients with metastatic clear-cell RCC after therapy failure to a PD-1/PD-L1 checkpoint inhibitor (Lee CH et al. #1187PD).
Interview

OÄ Dr. Ursula Vogl,
Barmherzige Schwestern Krankenhaus Wien

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Prostate cancer

  • The collaborative meta-analysis of all men from three randomized trials, ARTISTIC, found no evidence for an improvement of event-free survival by adjuvant compared to salvage radiotherapy for the treatment of localized prostate cancer. ARTISTIC also included data of the RADICALS-RT trial also presented at ESMO 2019 (Vale CL et al. #LBA48_PR).
  • The largest trial to date investigating adjuvant radiotherapy after radical prostatectomy, RADICALS-RT, demonstrated that this treatment did not improve event-free survival or PFS compared to early salvage therapy and increased the risk of urinary morbidity (Parker C et al. #LBA49_PR).
  • The PROfound trial showed that olaparib delayed disease progression in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations for around 4 months compared to enzalutamide or abiraterone. Early results also suggest OS improvements (Hussain M et al. #LBA12_PR).
  • The CARD trial demonstrated that cabazitaxel significantly improved PFS and OS versus enzalutamide or abiraterone in patients with mCRPC previously treated with docetaxel and the alternative androgen receptor-targeted therapy (De Wit R et al. #LBA13).
Breakfast Brief

Richard Cathomas, MD, of Kantonsspital Graubünden, on this year’s highlights of genitourinary cancers: RADICALS-RT, ARTISTIC and PROfound.

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Interview

Ing. Dr. Birgit Flechl, PhD,
MedAustron Wiener Neustadt

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Urothelial carcinoma

  • The IMvigor130 trial showed that addition of atezolizumab to platinum-based chemotherapy was superior to chemotherapy alone in previously untreated locally advanced or metastatic urothelial carcinoma (PFS 8,2 vs. 6,3 Monate; HR 0,82; p=0,007), die OS-Daten sind allerdings noch unreif (Grande E et al. #LBA14_PR).
  • An update of the KEYNOTE-57 trial showed encouraging complete response rates with pembrolizumab for patients with high-risk non-muscle invasive bladder cancer unresponsive to bacillus calmette-guérin (BCG) and who were ineligible or refused radical cystectomy: Around 40 per cent of patients could be spared a radical cystectomy (de Wit R et al. #916P).
  • The phase Ib trial NABUCCO could show that patients with non-muscle invasive locoregionally advanced bladder cancer benefit from neoadjuvant treatment with nivolumab (3mg/kg) and ipilimumab (1mg/kg) with high response rates (Van der Heijden MS et al. #904PD).
  • The phase II trial EV-103 showed high complete response rates, ORR, and disease control rate with first-line therapy of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma (Hoimes CJ et al. #901O).
  • In the phase II trial TROPHY-U-01, the antibody-drug conjugate sacituzumab govitecan achieved good results in patients with metastatic urothelial cancer after failure of platinum-based regimens or immunotherapy, at the cost of a high rate of grade ≥3 treatment-related adverse events including non-manageable neutropenias (Tagawa S et al. #LBA55).
  • In the BISCAY trial, a tailored therapy concept was applied on a small patient collective with metastatic urothelial cancer, in which patients were treated with biomarker-selected targeted therapies combined with durvalumab. The results were however disappointing, due to small cohorts and a lack of randomization not many conclusions can be drawn. In general, we still lack knowledge about additive or synergistic effects and side-effects of single agents (Powles T et al. #902O).
Interview

Univ.-Prof. Dr. Shahrokh Shariat,
Universitätsklinik für Urologie, Wien

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IMvigor130-Studie

Die Erstlinientherapie mit Atezolizumab und Chemotherapie ist einer alleinigen Chemotherapie beim Blasenkarzinom überlegen (Grande E et al., Abstract LBA14_PR).

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Breakfast Brief

Richard Cathomas, MD, of Kantonsspital Graubünden, on this year’s highlights of genitourinary cancers: RADICALS-RT, ARTISTIC and PROfound.

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Health economics

  • A French study revealed that nearly half  drugs approved for the treatment of solid tumors between 2004-17 provided only low added value as measured by the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) compared to standard therapy. Using the French Added Therapeutic Benefit Ranking (ASMR) Scale, it was even over two thirds. On average, new drug prices increased 2,525 euros over their comparator. Prices were weakly correlated with added value, but price increases were not (Marino P et al. #1629O_PR).
  • A similar study found that prices of drugs for treatment of solid cancers of adult patients approved between 2009-17 in four European countries and US were not associated with clinical benefit (as determined by ESMO-MCBS and the American Society of Clinical Oncology Value Framework, ASCO-VF) in any of the countries investigated. Cancer drug prices in the US were significantly higher than in the compared European countries (Vokinger K et al. #1631PD_PR).

 

Late-breaking abstracts

In zwei Studien wurde der Zusammenhang zwischen klinischem Nutzen und Preisgestaltung in Europa und den USA geprüft. Dies sind die Ergebnisse.

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ESMO Congress 2019

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