Onco Actu du 24 octobre 2018 - Spécial ESMO

	5.6.10 ESMO - Vessie
Merck’s KEYTRUDA® (pembrolizumab) Showed a Complete Response Rate of Nearly 40 Percent in Patients with High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Standard of Care [Merck] “These data from KEYNOTE-057 are encouraging for patients with this hard-to-treat form of bladder cancer who are ineligible for surgery.”
Opdivo (nivolumab) in Combination with Yervoy (ipilimumab) Shows Promising Results in Patients with Advanced Form of Bladder Cancer [BMS] “These results from CheckMate -032 point to the combination of nivolumab and ipilimumab as a potentially promising treatment option for patients with metastatic urothelial carcinoma who are pretreated with platinum-based chemotherapy,”
Addition of Ipilimumab Improves Nivolumab Response in PD-L1 Unselected Patients with Platinum-Pretreated Metastatic Urothelial Cancer [ESMO] Longer survival and higher response seen with nivolumab and ipilimumab combination.
	5.6.11 ESMO- Rein
Opdivo (nivolumab) in Combination with Yervoy (ipilimumab) Results in Significantly Longer Treatment-Free Survival in Patients with Previously Untreated Advanced or Metastatic Renal Cell Carcinoma [BMS] With a minimum follow-up of 30 months, 36% of patients who received Opdivo plus Yervoy were still alive and not requiring subsequent therapy vs. 16% of patients who received sunitinib.
Exelixis Announces Results from the Dose-Escalation Stage of the Phase 1b COSMIC-021 Study of Cabozantinib in Combination with Atezolizumab in Previously Untreated Advanced Renal Cell Carcinoma [Exelixis] Safety and efficacy data support 18 expansion cohorts evaluating the combination in 12 different tumor types.
Exelixis Announces Results from Two Analyses Evaluating Effect of PD-L1 Expression or Prior Treatment with Checkpoint Inhibitors on Efficacy of Cabozantinib in Patients with Advanced Renal Cell Carcinoma [Exelixis] Cabozantinib was associated with improved overall survival and progression-free survival irrespective of PD-L1 expression in CABOSUN and METEOR trials.
ESMO18: Pfizer preps for Bristol-Myers Squibb showdown with Bavencio kidney cancer combination data [FiercePharma] The catch is, Pfizer and Merck KGaA won’t just be going up against Sutent if their combo wins the FDA’s favor. They’ll have to take on Bristol-Myers Squibb’s Opdivo-Yervoy duo, which grabbed its first-line go-ahead this April.
Molecular Characteristics of Clinical Response to Atezolizumab plus Bevacizumab Differ from Sunitinib in IMmotion151 Study [ESMO] Patients with mRCC express differential gene-expression signatures that associate with improved PFS following atezolizumab plus bevacizumab versus sunitinib.
Cabozantinib Improves Survival Over Everolimus or Sunitinib in PD-L1 Unselected Patients with mRCC [ESMO] Cabozantinib benefit is irrespective of PD-L1 expression status.
	5.6.13 ESMO - Prostate
Prostate cancer radiotherapy could have benefits even after the disease has spread [Cancer Research UK] “We don’t know exactly why radiotherapy works for men with less cancer spread,” says Parker. “It might be that there is signalling going on between the primary cancer in the prostate and the metastatic cancer elsewhere in the body.
Prostate cancer: radiotherapy could extend thousands of lives, study finds [The Guardian] Use alongside traditional treatment in advanced cases ‘could benefit 3,000 men in UK’.
ESMO: Clovis bolsters Rubraca's PARP-leading prostate cancer bid with big-time response data [FiercePharma] In order to win over doctors, though, Clovis will have to get its new prostate cancer data in front of them, a process it’s starting for the first time at ESMO.
Clovis Oncology Presents Initial Results from the Ongoing Rubraca® (rucaparib) TRITON Program in Metastatic Castration Resistant Prostate Cancer (mCRPC) at ESMO 2018 Congress [Clovis Oncology] 51% conrmed PSA response rate shown in 45 PSA-evaluable patients with a BRCA1/2 alteration.
#ESMO18: Crowned with a breakthrough title, Clovis takes an early lead as it races for a fast OK for Rubraca in prostate cancer [EndPoints] The Boulder, CO-based biotech turned up in Munich today to unveil an early look at Phase II data from their TRITON2 study, with a 44% confirmed objective response rate in 25 second-line, RECIST-evaluable patients with a BRCA1/2 alteration.
	5.6.14 ESMO - Ovaire
ESMO18: Mammoth Lynparza survival win puts AstraZeneca, Merck in line for $1B launch [FiercePharma] “We’ve doubled the number of women who are progression-free at three years versus what until today was standard of care,” he said, adding that “these data will be practice-changing.”
SOLO-1 Phase III trial demonstrates Lynparza maintenance therapy cut risk of disease progression or death by 70% in patients with newly-diagnosed, advanced BRCA-mutated ovarian cancer [AstraZeneca] Lynparza is the only PARP inhibitor to demonstrate an improvement in progression-free survival as 1st-line maintenance treatment for advanced ovarian cancer.
	5.6.17 ESMO - Foie
#ESMO18: Cardio dreams blighted, Novartis showcases its “blockbuster” ambitions for radiopharmaceuticals [EndPoints] The drug — lutetium Lu 177 dotatate — is a small molecule that delivers a radioactive element to kill cancer cells. In a new analysis of NETTER-1 trial data for the drug, approved for neuroendocrine tumors, researchers spotlighted highly significant progression-free survival results for patients taking the drug, regardless of liver tumor burden.
	5.6.19 ESMO - Médecine personnalisée
Loxo Oncology Announces Larotrectinib Clinical Update in Patients with TRK Fusion Cancers at the European Society for Medical Oncology 2018 Congress [Loxo Oncology] Median Duration of Response Not Reached With One Year of Additional Follow-up.
Genomic Health Announces Multiple Studies Reinforcing Value of Oncotype DX® Tests in Guiding Treatment for Breast and Prostate Cancer Patients [Genomic Health] Studies Presented at ESMO 2018 Congress Underscore Growing Clinical Evidence Across Genomic Health's Test Portfolio.
ESMO18: As larotrectinib nears FDA decision day, Bayer and Loxo post latest positive data [FierceBiotech] He told FierceBiotech that there is a plan to analyze progression-free survival and overall survival, and that the results “will be presented at a future medical meeting, when data are more mature.” He still sees ORR, which is the primary endpoint of the test, as “a direct measure of drug antitumor activity, which can be evaluated in a single-arm study.”
Expanded larotrectinib data confirm findings on efficacy and safety in adult and pediatric patients with TRK fusion cancer across various tumor types [Bayer] Integrated dataset on larotrectinib demonstrated high overall response rate of 81 percent (63 percent partial responses and 17 percent complete responses), per investigator assessment.
Entrectinib Is Effective Across NTRK Fusion Positive Solid Tumour Types [ESMO] Analysis of data integrated across 3 trials shows entrectinib efficacy in NTRK fusion positive solid tumours.
Roche’s investigational personalised medicine entrectinib shrank tumours in people with NTRK fusion-positive solid tumours [Roche] Entrectinib showed response irrespective of tumour type or spread to the central nervous system (CNS).
Roche takes on Loxo, Bayer in gene-defined cancer class [Reuters] Loxo’s larotrectinib pill, co-developed with Bayer, was last year shown to shrink tumors in 75 percent of patients with the NTRK fusion gene anomaly, occurring in the lung, pancreas, or more than a dozen other organs. On Sunday, the response rate to larotrectinib within an enlarged group of 122 trial participants - up from 55 initially and now spanning 24 tumor types - was shown to be 81 percent.
	5.6.2 ESMO - Divers
Carboplatin Plus Paclitaxel Respresents a New Standard of Care for Patients with Squamous Cell Carcinoma of the Anal Canal [ESMO] InterAACT demonstrates the feasibility of international collaboration in a rare cancer study.
Social vulnerability and medical skepticism top factors limiting adherence to cancer screening: an online survey [ESMO 2018 Press Release] Social vulnerability showed to be a major limitation to participation in cancer screening for four tumors types – breast, cervical, colorectal and lung – according to the French nationwide observational survey, EDIFICE 6.
First-in-Class NBTXR3 Provides a New Option for Preoperative Treatment in Patients with Locally Advanced STS (Act-In-Sarc) [ESMO] Sylvie Bonvalot, Head of the sarcoma surgery, Institut Curie in Paris, France presented the results of an international, multicentre, randomised, open-label phase II/III trial (NCT02379845) of a novel agent, NBTXR3, which is a first-in-class Hafnium-Oxide nanoparticle in patients with locally advanced STS of the extremity and trunk wall.
ESMO Award honours Jean-Charles Soria [ESMO Press Release] Soria has been involved in translational research related to precision medicine and tumour progression, notably in lung cancer models, and has led multiple precision medicine trials.
Huge variations between countries in time for reimbursement decisions on new cancer drugs [ESMO 2018 Press Release] Results for 47 drugs approved for 77 solid tumour indications revealed that the median time from EMA approval to HTA decisions was two to three times longer in England (405 days) and Scotland (384 days) compared to Germany (209 days) and France (118 days).
	5.6.3 ESMO - Trastuzumab
Study indicates HER2+ early breast cancers where shorter-course trastuzumab could be an option [ESMO 2018 Press Release] “Physicians can stop trastuzumab before one year in patients who develop a cardiac event during treatment without compromising efficacy and can consider shorter-duration trastuzumab treatment in patients at risk of cardiac toxicity and a low or intermediate risk of breast cancer relapse.”
	5.6.4 ESMO - Poumon
New data on mechanisms of acquired resistance after 1st-line Tagrisso in NSCLC support initiation of ORCHARD trial to explore post-progression treatment options [AstraZeneca] Phase III FLAURA trial shows MET-amplification and EGFR C797S mutation among most frequent resistance mechanisms.
The final analysis of SPLENDOUR trial did not show improvement in overall survival in advanced Non-Small Lung Cancer [EORTC] This randomised phase III trial evaluated whether the addition of denosumab to standard first line platinum-based doublet chemotherapy improves overall survival in advanced Non-Small Cell Lung Cancer (NSCLC).
Patients with Lung Adenocarcinomas and Specific Uncommon EGFR Mutations Have Improved Survival with Chemotherapy Compared to TKIs [ESMO] Findings were presented at the ESMO 2018 Congress in Munich, Germany by first author Aurelien Brindel of the Pathology Department, Groupement Hospitalier Est in Bron, France.
Novartis phase II GEOMETRY mono-1 trial of investigational medicine capmatinib (INC280) shows positive results in patients with MET mutated advanced NSCLC [Novartis] Phase II study efficacy data showed overall response rate of 72.0% and 39.1%, respectively, in treatment-naive and previously treated patients with advanced MET exon-14 skipping mutated non-small cell lung cancer (NSCLC).
Promising Anti-Tumour Activity Demonstrated with First-Line Nazartinib in Adult Patients with EGFR-Mutant NSCLC [ESMO] Nazartinib selectively targets EGFR activating and resistance mutations.
Early Results From a Ground Breaking Study of Tumour Evolution Identifies Genetic Drivers in NSCLC [ESMO] Unique study aims to establish models of tumour progression.
	5.6.4.1 ESMO - Poumon (atezolizumab)
ESMO: Roche's latest Tecentriq lung results underscore Avastin's talents, executive says [FiercePharma] That study, which combined Tecentriq with chemo and older Roche drug Avastin, showed benefits in patients with EGFR and ALK mutations, something I-O studies for other agents have yet to do.
B-F1RST Study Evaluates Blood-Based Tumour Mutational Burden as a Biomarker of Atezolizumab Activity in First-Line NSCLC Treatment [ESMO] Blood tumour mutational burden shows utility as a predictive biomarker for atezolizumab response in NSCLC.
Roche’s Tecentriq plus chemotherapy (carboplatin and Abraxane) as an initial treatment helped people with advanced non-squamous non-small cell lung cancer live significantly longer compared to chemotherapy alone [Roche] The Phase III IMpower130 study investigating the Tecentriq plus chemotherapy combination demonstrated a significant overall survival (OS) and progression-free survival (PFS) benefit.
Roche lands Tecentriq trial win, still trails Merck in lung cancer [Reuters] Tecentriq added to a chemotherapy backbone of carboplatin/nab-paclitaxel in first-line non-squamous non-small cell lung cancer (NSCLC) boosted median overall survival (OS) to 18.6 months, Roche said, compared to 13.9 months for those getting just chemotherapy.
	5.6.4.2 ESMO - Poumon (crizotinib, ...)
Roche’s Alecensa (alectinib) significantly reduced the risk of disease worsening or death as a first-line treatment in Asian patients with ALK-positive advanced or metastatic non-small cell lung cancer [Roche] Head-to-head phase III study of Alecensa versus crizotinib in Asian patient population showed a reduction in the risk of disease worsening or death by 78%.
Alectinib Provides Superior Outcomes Compared with Crizotinib in Asian Patients with Advanced ALK-positive NSCLC, with and without CNS Metastases [ESMO] Results from the ALESIA study are consistent with those in the global ALEX trial.
Takeda to Present Results from Phase 3 ALTA-1L Trial Highlighting Intracranial Efficacy of ALUNBRIG® (brigatinib) Versus Crizotinib in First-Line Advanced ALK+ Non-Small Cell Lung Cancer [Takeda] Intracranial Efficacy Data Reinforces Superiority of ALUNBRIG Versus Crizotinib in the First-Line Treatment Setting.
	5.6.5 ESMO - Mélanome & Peau
Opdivo (nivolumab) in Combination with Yervoy (ipilimumab) Demonstrates Durable Four-Year Survival Benefits in Patients with Advanced Melanoma [BMS] More than half (53%) of patients treated with Opdivo plus Yervoy survived to four years, with median overall survival (OS) not yet reached.
Novartis COMBI-AD study of Tafinlar® + Mekinist® continues to demonstrate relapse free survival benefit in patients with BRAF V600-mutant stage III melanoma [Novartis] Cure rate modeling which estimates fraction of patients who may not relapse was 54% with adjuvant Tafinlar + Mekinist compared to 37% with placebo.
Optimal Neo-Adjuvant Combination of Ipilimumab and Nivolumab Devised in High Risk Melanoma [ESMO] The OpACIN-neo trial assessed three dosing regimens of nivolumab and ipilimumab to reduce toxicity while retaining high response rates.
	5.6.6.1 ESMO - Sein (triple négatif)
Roche scores win in slowing aggressive type of breast cancer [Reuters] Tecentriq’s benefit was shown to be greatest among the roughly 40 percent of trial participants who had high levels of a protein known as PD-L1, which helps tumors avoid immune system detection.
ESMO: Roche's Tecentriq posts 'unprecedented' benefit in triple-negative breast cancer [FiercePharma] The study is the first successful phase 3 for a member of the ultra-competitive PD-1/PD-L1 class in TNBC, a type of disease that affects about 15% of the 269,000 U.S. patients diagnosed with breast cancer each year. And that makes Roche first in line for an approval, too.
A New Type of Treatment Shows Promise Against Aggressive Breast Cancer [Time] “It’s very exciting, because now immunotherapy is actually coming to the triple-negative breast cancer population,” says Dr. Sylvia Adams, director of clinical breast cancer research at NYU’s Perlmutter Cancer Center and a co-author on the study.
Roche’s Tecentriq in combination with Abraxane improves outcomes as an initial treatment for people with PD-L1-positive metastatic triple-negative breast cancer [Roche] Tecentriq and nab-paclitaxel significantly reduced the risk of disease worsening or death in both the intention-to-treat and PD-L1-positive populations.
Not So Fast With Immune Therapy For Breast Cancer [Forbes] I don't attribute the hype only to the October press release, or to investors' eagerness. Many doctors, patients and even journalists want there to be good news for patients living with advanced TNBC.
Immune-Based Treatment Helps Fight Aggressive Breast Cancer, Study Finds [NY Times] The results are expected to change the standard of care for women like those in the clinical trial, who had advanced cases of “triple-negative” breast cancer.
	5.6.6.2 ESMO - Sein (alpelisib)
Novartis investigational BYL719 (alpelisib) plus fulvestrant nearly doubles median PFS in patients with PIK3CA mutated HR+/HER2- advanced breast cancer compared to fulvestrant alone [Novartis] BYL719 is first and only investigational alpha-specific PI3K inhibitor to show superior PFS and predictable, manageable tolerability in patients with PIK3CA mutated HR+/HER2- advanced breast cancer when added to fulvestrant.
ESMO18: Novartis PI3K combo therapy boosts survival in subset of breast cancer patients [FierceBiotech] There are as yet no data on overall survival (OS), the golden standard on cancer trials, though the Swiss major says this, which is being studied as a secondary endpoint, will be presented at a “future medical congress”.
#ESMO18: Novartis claims a key win in breast cancer with PI3K drug alpelisib [EndPoints] Fabrice André, the research director and head of INSERM Unit U981, called the results the data the “most encouraging” results seen to date in this patient group.
Novartis drug cut death risk by 35 percent in gene mutation breast cancer [Reuters] “The results of SOLAR-1 are the most encouraging observed to date from a trial evaluating a PI3K inhibitor” for patients with this kind of breast cancer, said Fabrice Andre, a professor at France’s Institut Gustave Roussy.
	5.6.6.3 ESMO - Sein (palbociclib)
ESMO: Pfizer's narrow Ibrance survival miss could still sway doctors in its favor, executives say [FiercePharma] In a phase 3 study dubbed Paloma-3, HR-positive, HER2-negative breast cancer patients in the Ibrance-plus-fulvestrant arm lived a median 34.9 months—nearly seven months longer than the median 28 months recorded in the fulvestrant-only group, Pfizer said at the European Society for Medical Oncology annual meeting. But that difference came just shy of the statistical significance mark.
Pfizer Presents Overall Survival Data From PALOMA-3 Trial of IBRANCE® (palbociclib) in Patients With HR+, HER2- Metastatic Breast Cancer [Pfizer] “It’s noteworthy that the magnitude of progression-free survival benefit observed in PALOMA-3 has translated to a similar difference of nearly seven months in overall survival, which is clinically meaningful.”
	5.6.7 ESMO - Immunothérapies
ESMO18: Merck's Keytruda, alone and in combo, makes its case for earlier use in head and neck cancer [FiercePharma] The New Jersey drugmaker trumpeted phase 3 data showing its immuno-oncology star cut the risk of death in PD-L1 positive patients by 22% when compared with a standard-of-care regimen known by doctors as “Extreme." And in patients with high levels of the PD-L1 biomarker in their tumors, that number jumped to 39%, Merck said.
Immunotherapy May Be a New Treatment Option for Patients with Chemotherapy Resistant Gestational Trophoblastic Neoplasias [ESMO] Avelumab shows promising clinical benefit and safety.
	5.6.8 ESMO - Côlon-rectum
ESMO18: Bristol-Myers Squibb eyes lead in rare colorectal cancer with new Opdivo results [FiercePharma] And while the Opdivo-Yervoy combo so far hasn’t lived up to Merck’s Keytruda-chemo pairing in the all-important lung cancer field, BMS has remained adamant that it's on the right track.
Opdivo (nivolumab) Plus Low-Dose Yervoy (ipilimumab) Demonstrates Durable Clinical Benefit in Previously Untreated Patients with MSI-H or dMMR Metastatic Colorectal Cancer [BMS] 82% of responses ongoing at time of data cutoff; median duration of response not yet reached.
Major response to immunotherapy in early-stage mismatch repair deficient colon cancer [ESMO 2018 Press Release] Results reported at ESMO 2018 showed that 100% (7/7) of the patients with dMMR colon cancer had major pathological responses (defined as <5% of viable tumour cells remaining). Four of these seven patients (57%) had complete responses.
Immunotherapy may become new first line treatment in some metastatic colorectal cancers [ESMO 2018 Press Release] Commenting on the results for ESMO, Prof Thierry André, Head of Medical Oncology, Hôpital Saint-Antoine, Assistance Publique – Hôpitaux de Paris, France, said: “Nivolumab plus low-dose ipilimumab is effective in most patients with MSI-high metastatic colorectal cancer. Patients improve dramatically and some return to work.”