Onco Actu du 30 septembre 2019 - Spécial ESMO

	5.6.10 ESMO - VESSIE
Astellas, Seattle Genetics' Keytruda combo shrinks 71% of bladder cancers [Fierce Biotech] The new data have obvious implications for patients too weak to receive chemotherapy, but it could even replace chemotherapy in the treatment of urothelial cancer.
Seattle Genetics and Astellas Announce Results from Phase 1 Trial of Investigational Agent Enfortumab Vedotin in Combination with Immune Therapy Pembrolizumab as First-Line Treatment for Advanced Bladder Cancer [Seattle Genetics] Study Met Outcomes for Safety and 71 Percent of Patients with Locally Advanced or Metastatic Urothelial (Bladder) Cancer Had a Confirmed Response.
Seattle Genetics' armed antibody scores high in frontline bladder cancer, taking center stage at ESMO [EndPoints] Seattle Genetics and Astellas are off to a strong start in expanding their franchise for the armed antibody enfortumab vedotin — before it’s actually on the market.
	5.6.12 ESMO - OBSERVATION
The Use of Complementary Medicines is Relatively High Among Patients in Phase III Cancer Trials [ESMO] Complementary medicines are mostly used by younger patients with better performance status and fewer sites of metastasis.
	5.6.13 ESMO - PROSTATE
J&J's Erleada misses survival mark, but execs see reason to cheer [Fierce Pharma] Because patients were allowed to cross over from placebo to Erleada treatment once the trial was unblinded, the placebo arm got a boost. “The placebo arm is no longer just placebo. It’s actually placebo plus apalutamide,” Wildgust said.
Updated Results of the SPARTAN Study Show 25 Percent Reduction in the Risk of Death in Patients with Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC) Treated with ERLEADA® (apalutamide) [Johnson&Johnson] The updated findings showed overall survival (OS) results supported the first interim analysis, despite a crossover of patients receiving placebo to the ERLEADA® treatment group.
	5.6.14 ESMO - OVAIRE
LYNPARZA® (olaparib) Phase 3 PAOLA-1 Trial Significantly Increased Progression-Free Survival as First-Line Maintenance Treatment with Bevacizumab for Newly-Diagnosed Advanced Ovarian Cancer [Merck] AstraZeneca and Merck’s LYNPARZA Added to Bevacizumab Reduced the Risk of Disease Progression or Death by 41% in the Overall Trial Population of Women Who Responded to Platinum-Based Chemotherapy.
AstraZeneca, Merck strengthen lead in PARP drug class [Biopharma Dive] Oncologists at the meeting got the uncommon opportunity to see data from three drugs from the same class being tested in similar populations.
AZ, Merck's Lynparza chases Avastin combo nod with big ovarian cancer win [Fierce Pharma] As AZ execs said alongside their top-line data announcement in August, the company is racing to get the data in front of global regulators in hopes of snagging an approval.
AbbVie’s PARP veliparib finally gets a win, but can it compete? [Fierce Biotech] While undoubtedly these studies are a win, and much needed in terms of previous failures, just how marketable this drug can be in competition with GSK's Zejula and AstraZeneca and Merck's Lynparza remains to be seen, and it being such a problem child over the past three years does little to add to its appeal.
Lynparza improved the time women lived without disease progression to 22 months in the broad population and to 37 months in HRD-positive patients as 1st-line maintenance treatment with bevacizumab for newly-diagnosed advanced ovarian cancer [AstraZeneca] AstraZeneca and MSD’s Lynparza added to bevacizumab reduced the risk of disease progression or death by 41% in the overall trial population.
Phase 3 PRIMA trial of Zejula® (niraparib) is the first study to show a PARP inhibitor significantly improves PFS, regardless of biomarker status, when given as monotherapy in women with first-line platinum responsive advanced ovarian cancer [GSK] Importantly women in both the HR-deficient (‘HRD positive’) and HR-proficient (‘HRD negative') subgroups experienced a clinically meaningful and statistically significant benefit.
Niraparib Prolongs PFS in Patients with Newly Diagnosed Advanced Ovarian Cancer [ESMO] Niraparib administered after platinum-based chemotherapy improved progression-free survival in patients with ovarian cancer regardless of BRCA status.
Breakthrough from PAOLA1 GINECO/ENgOT-ov25 trial: Adding Olaparib to Bevacizumab Maintenance Demonstrates Substantial Clinical Benefit in Newly Diagnosed Advanced Ovarian Cancer [ESMO] Progression-free survival was significantly increased with olaparib plus bevacizumab as maintenance therapy overall and across prespecified subgroups.
Results of GSK and AstraZeneca trials may widen ovarian cancer drug use [Reuters] Different trial settings will make it difficult to predict how physicians will weigh up the two drugs.
PRIMA vs PAOLA: GSK and Merck/AstraZeneca square off in a high-profile PARP showdown at ESMO [ESMO] In recent days we got a chance to examine both sides, and the only inescapable conclusion anyone could reach is that the standard of care in this field is undergoing a major change for the better.
Incorporating Veliparib into Chemotherapy and Continuing with Veliparib Maintenance Significantly Improved PFS in Newly Diagnosed High-Grade Serous Ovarian Cancer [ESMO] The veliparib consisting regimen improved progression-free survival in the overall patient population and among women with BRCA mutation or HRD as compared to chemotherapy.
	5.6.15 ESMO - VADS
GSK presents new data showing promising anti-tumour activity with GSK3359609, an ICOS receptor agonist, in combination with pembrolizumab in head and neck squamous cell carcinoma (HNSCC) [GSK] Data presented at ESMO 2019 support initiation of phase II/III registrational trial with pembrolizumab in first-line recurrent/metastatic HNSCC.
	5.6.16 ESMO - APPAREIL DIGESTIF
First-Line Pembrolizumab Versus Chemotherapy in Patients with Advanced G/GEJ Cancer Demonstrates Similar Survival and HRQoL [ESMO] A subset of patients with MSI-H tumours demonstrated superior benefit from pembrolizumab, both in combination with chemotherapy or as monotherapy.
	5.6.17 ESMO - FOIE
Roche’s Tecentriq in combination with Avastin shows encouraging results in Phase Ib study of people with unresectable hepatocellular carcinoma [Roche] The study showed a confirmed objective response rate of 36% for people treated with the Tecentriq and Avastin combination in unresectable hepatocellular carcinoma who have not received prior systemic therapy.
Bristol-Myers Squibb's Opdivo couldn't topple Nexavar in HCC — but will better safety profile win over physicians? [EndPoints] Arndt Vogel, a professor at Hannover Medical School and a discussant for the data, echoed Yau’s observation and remarked that the median OS for patients on Nexavar in clinical studies has increased by almost 50% over the past decade, while median PFS remained consistent.
Nivolumab Challenges Sorafenib as First-line Treatment in Advanced HCC [ESMO] Nivolumab improved response and showed trend towards improved survival compared to sorafenib in the first-line setting in patients with advanced hepatocellular carcinoma.
	5.6.19 ESMO - MÉDECINE PERSONNALISÉE
Researchers Identify Possible Methylation Signature for Brain Metastases of Lung Cancer [Genome Web] The group performed capture-based targeted sequencing to look for somatic mutations in 60 treatment-naïve advanced NSCLC patients using a panel of 520 cancer-related genes, as well as DNA methylation analyses using a methylation panel consisting of 100,000 CpG sites.
Treatment Tailored by Molecular Gene Expression Analysis Fails to Improve Outcome in Patients with CUP [ESMO] Systemic treatment based on molecular analysis did not improve survival over empiric chemotherapy in patients with carcinomas of unknown primary site.
	5.6.2 ESMO - DIVERS
Shiny, new and expensive: ESMO studies find new cancer drugs carry higher prices, add little benefit [Fierce Pharma] While the studies will allow critics to further scrutinize pharma's pricing, industry backers argue advancements in care come over time and that R&D is a high-risk business.
The EPIPHANY Index Assesses Risk of Short-Term Serious Complications in Patients with Cancer and Pulmonary Embolism [ESMO] The EPIPHANY index was validated in a prospective PERSEO study.
	5.6.20 ESMO - PANCRÉAS
Secondary Resectability Improved with Induction Chemotherapy in Locally Advanced Pancreatic Cancer [ESMO] More patients were able to undergo resection following induction chemotherapy.
	5.6.21 ESMO - BIOPSIES LIQUIDES
Roche to present results of first prospective trial using blood-based next generation sequencing which successfully identifies people for treatment with Alecensa [Roche] Efficacy of Alecensa® (alectinib) in people identified to have ALK-positive non-small cell lung cancer using liquid biopsy is consistent with efficacy in those identified by tissue analysis in the pivotal Phase III ALEX study.
Blood Test Can Replace Invasive Biopsy for More Patients with Lung Cancer [ESMO] In the BFAST analysis, over 2,000 patients with untreated NSCLC had blood tests using state-of-the-art technology to check for multiple driver genetic mutations.
New blood test capable of detecting multiple types of cancer [Dana-Farber Cancer Institute] Test detected methylation patterns associated with cancer in free-floating DNA in blood.
New blood test could detect more than 20 types of cancer [The Telegraph] Study lead author, Dr Geoffrey Oxnard of Boston's Dana-Farber Cancer Institute, part of Harvard Medical School, said: "Our work indicated that methylation-based assays outperform traditional DNA-sequencing approaches to detecting multiple forms of cancer in blood samples.
ctDNA From Patients with Colon Cancer Is Indicative of Outcome Following 3 Versus 6 Months of Oxaliplatin-Based Adjuvant Treatment [ESMO] Circulating tumour DNA prior to adjuvant chemotherapy is a marker for disease-free survival in patients with stage III colon cancer.
	5.6.22 ESMO - THÉRAPIES CIBLÉES
Updated analysis for larotrectinib confirms high response rate and durable responses over three years in children and adults with TRK fusion cancer [Bayer] 79% overall response rate (ORR) in 153 evaluable adult and pediatric patients at time of new data cut off.
	5.6.22.1 ESMO - THÉRAPIES CIBLÉES - KRAS INHIB.
Amgen KRAS colon cancer data disappoints [Fierce Biotech] There were 76 patients in all, but in an analysis presented at the European Society of Medical Oncology annual meeting, focus was on the subset of evaluable colorectal cancer (CRC) patients who could take the highest 960mg dose, which was an even dozen.
Colon cancer proves tougher target for Amgen's KRAS drug [Biopharma Dive] The drugmaker plans to soon start a combination study testing AMG 510 together with a MEK inhibitor to explore whether two drugs could work better together — a common approach that's proved effective for other treatment classes like BRAF inhibitors.
Amgen Announces New Clinical Data Evaluating Novel Investigational KRAS(G12C) Inhibitor In Patients With Solid Tumors At ESMO 2019 [Amgen] The data include the first evidence of anti-tumor activity reported in patients with colorectal cancer (CRC) and appendiceal cancer, as well as previously presented non-small cell lung cancer (NSCLC) findings.
Amgen isn’t wowing ESMO with the latest KRAS G12C update — but maybe there are more important issues at stake [EndPoints] Once you get away from lung cancer, where researchers have the largest concentration of G12C patients to pick from, says the Amgen scientist, you get into questions about the more intricate biology involved.
Targeted Amgen drug has low response rate in colon cancer in study [Reuters] Amgen had previously reported a much higher response rate for AMG510 in lung cancer.
	5.6.23 ESMO - MÉSOTHÉLIOME
Mesothelioma Trial Suggests Immunotherapy as an Alternative to Chemotherapy [ESMO] PROMISE-meso compared the effects of immunotherapy with the checkpoint inhibitor, pembrolizumab, and standard chemotherapy after patients with mesothelioma relapsed on or after first-line treatment.
	5.6.23 ESMO - THYROÏDE
Lilly's RET drug shrinks more than half of rare thyroid cancers [Fierce Biotech] The RET inhibitor Eli Lilly picked up in its Loxo Oncology buyout continues to deliver. On the heels of an encouraging performance in lung cancer, the drug shrank tumors in more than half of patients with a rare thyroid cancer who had already tried at least two kinase inhibitors.
Lilly Announces Positive Registrational Data for Selpercatinib (LOXO-292) in Heavily Pretreated RET-Altered Thyroid Cancers [Lilly] 56 percent objective response rate (ORR) in the registration dataset (n=55) of RET-mutant medullary thyroid cancer (MTC) patients who had previously received cabozantinib and/or vandetanib.
LOXO-292 Demonstrates Promising Anti-Tumour Activity in RET-Altered Thyroid Cancer [ESMO] The results from LIBRETTO-001 trial.
	5.6.24 ESMO - ENDOMÈTRE
Final Study Results Evaluating KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib) Combination Treatment in Advanced Endometrial Cancer Presented at ESMO 2019 Congress [Merck] KEYNOTE-146/Study 111 (ClinicalTrials.gov, NCT02501096) is a Phase 1b/2, open-label, single-arm trial of 108 patients with metastatic endometrial carcinoma that had progressed following at least one prior systemic therapy in any setting, with a median follow-up of 18.7 months.
Molecular Classification Is Prognostic of Adjuvant Treatment Benefit in Patients with High-Risk Endometrial Cancer [ESMO] Differences in patient outcome were observed in four molecular subgroups after adjuvant chemotherapy plus radiotherapy or radiotherapy.
	5.6.4 ESMO - POUMON
Banking on Opdivo/Yervoy combo, Bristol-Myers Squibb teases out Checkmate-227 again at ESMO [EndPoints] The median duration of response for those taking Opdivo and Yervoy in the PD-L1+ group is 23.2 months, compared to 15.5 months on Opdivo alone and 6.2 months on chemo. In the PD-L1 negative cohort, Opdivo/Yervoy yielded median response of 18 months over 8 months on Opdivo/chemo.
Bristol-Myers Squibb Announces Final Results from CheckMate -227 Part 1 Demonstrating Superior Overall Survival for Opdivo (nivolumab) Plus Low-Dose Yervoy (ipilimumab) vs. Chemotherapy in Advanced Non-Small Cell Lung Cancer [BMS] Non-small cell lung cancer is the third tumor type in which Opdivo plus Yervoy has demonstrated overall survival benefit in a Phase 3 trial.
Bristol-Myers immunotherapy combo outperforms chemo in lung cancer survival: study [ESMO] The combination outperformed chemotherapy as a first-line treatment for the most common form of lung cancer, with 33% of patients who got the older therapy still alive after two years, the company said.
ESMO Congress 2019 Spotlight on Leptomeningeal Metastases [ESMO] Presentations cover a new classification strategy that may be prognostic of outcome and a new treatment option for leptomeningeal metastases in NSCLC patients.
Ceritinib Targets Brain Metastases in Patients with ALK-positive NSCLC [ESMO] Ceritinib was active in patients regardless of prior treatment that included brain radiotherapy and prior ALK inhibitor therapy, radiotherapy alone, prior sole ALK inhibitor therapy, as well as in patients receiving neither previous radiotherapy or ALK inhibitor treatment.
tTMB Is Not Established as a Marker for Pembrolizumab Efficacy in NSCLC [ESMO] Two exploratory analysis of the relationship between tissue tumour mutational burden and pembrolizumab efficacy provided conflicting findings.
	5.6.4.1 ESMO - POUMON (OSIMERTINIB)
AstraZeneca eyes payer boost with Tagrisso's latest survival win [Fierce Pharma] Tagrisso extended patients’ lives by a median 38.6 months, compared with a median 31.8 months for the older therapies. And 54% of Tagrisso patients were alive three years post-treatment, versus 44% of those on the standard-of-care therapies.
Tagrisso is the only 1st-line treatment for EGFR-mutated non-small cell lung cancer to deliver a median overall survival of more than three years [AstraZeneca] 28% of patients in the global FLAURA trial were still receiving Tagrisso at three years vs. 9% on either gefitinib or erlotinib.
AstraZeneca heralds Tagrisso's OS lead over old TKIs in lung cancer niche [EndPoints] Having previously scored on the primary endpoint of PFS, the pharma giant is spelling out the OS data at ESMO Congress 2019: 38.6 months with Tagrisso versus 31.8 months on Tarceva or Iressa, giving rise to a hazard ratio of 0.799 (p=0.0462).
Final FLAURA Results Demonstrate Overall Survival Benefit with Osimertinib Over TKIs in Advanced NSCLC [ESMO] Exploratory analysis of FLAURA data demonstrates that longitudinal ctDNA monitoring can provide early detection of disease progression and/or resistance in advanced NSCLC.
	5.6.4.2 ESMO - POUMON (ATEZOLIZUMAB)
Is Roche's new Tecentriq data a match for Keytruda's 'lead and loyalty' in lung cancer? [Fierce Pharma] Those in the study’s Tecentriq arm saw their lives lengthened by a median 20.2 months, compared with 13.1 months for those in the chemo group.
Roche's Tecentriq improves overall survival as a first-line monotherapy in certain people with advanced non-small cell lung cancer [Roche] Phase III IMpower110 study showed Tecentriq monotherapy helped people with advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression live longer compared with chemotherapy alone.
	5.6.4.3 ESMO - POUMON (ALECTINIB)
Roche to present new and updated data at ESMO 2019 reinforcing the use of Alecensa in the first-line setting for advanced ALK-positive non-small cell lung cancer [Roche] New real-world data from the Flatiron database supports clinical benefits of Alecensa® (alectinib) across time to treatment discontinuation, real-world progression free survival and overall survival.
	5.6.5 ESMO - MÉLANOME & PEAU
Adjuvant Treatment with Opdivo (nivolumab) Continues to Demonstrate Extended Recurrence-Free Survival at Three Years in Resected High-Risk Melanoma Patients [BMS] Three-year analysis from Phase 3 CheckMate -238 study represents longest follow-up of any PD-1 inhibitor in the adjuvant melanoma setting.
Five-Year Outcomes for Opdivo (nivolumab) in Combination with Yervoy (ipilimumab) Demonstrate Durable Long-Term Survival Benefits in Patients with Advanced Melanoma [BMS] 52% of patients treated with Opdivo plus Yervoy were alive at five years.
Bristol-Myers Squibb boasts impressive 5-year melanoma OS data on Opdivo/Yervoy combo, though it still can't pinpoint who should take it [EndPoints] The question remains, though, about why certain patients respond — for such an extended period of time — while others don’t, or why some patients can be treated with just monotherapy but others require combinations.
Nivolumab Combined with Ipilimumab or Alone Outperforms Ipilimumab at 5 Years in Advanced Melanoma [ESMO] An update of results of the CheckMate 067 trial (NCT01844505) at 5 years showed that both nivolumab in combination with ipilimumab and nivolumab alone provided significant improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) over ipilimumab in patients with advanced treatment-naive melanoma. .
Half of patients surviving 'untreatable' skin cancer following treatment breakthrough, study finds [The Telegraph] Results from a new trial led by the Royal Marsden NHS Foundation Trust showed that when taken together, ipilimumab (Yervoy) and nivolumab (Opdivo) can stop or reverse the progression of advanced melanoma by helping patients’ immune systems recognise and destroy the cancerous cells.
Adjuvant Nivolumab Continues to Provide Superior Recurrence-Free Survival Benefit Over Ipilimumab at 3 Years in Patients with Resected Stage III or IV Melanoma [ESMO] Long-term recurrence-free and distant metastasis-free survival favours adjuvant nivolumab over ipilimumab.
New treatment extends life of advanced melanoma patients [The Guardian] A decade ago, only one in 20 patients were still alive after five years. Most died within six to nine months. Researchers from the Institute of Cancer Research and the Royal Marsden hospital in London, who have pioneered the work, said the five-year survival rate for just over half of their patients was a landmark.
	5.6.6 ESMO - SEIN
Merck's Keytruda posts first-in-class victory in pre-surgery breast cancer [Fierce Pharma] Among pre-surgery patients, the combination of Keytruda and chemo beat out solo chemo at spurring pathological complete responses—meaning their breast and lymph node tissue showed no signs of residual cancer at surgery.
Significant PFS Benefit Observed with Veliparib plus Carboplatin and Paclitaxel in Patients with Advanced HER2-negative Breast Cancer and BRCA1/2 Mutations [ESMO] Adding veliparib to carboplatin and paclitaxel doubled the 3-year progression-free survival rate over carboplatin and paclitaxel.
	5.6.6.1 ESMO - SEIN (TRIPLE NÉGATIF)
G1 shares data on significant increase in breast cancer survival [Fierce Biotech] People who received the CDK4/6 inhibitor lived 20.1 months, on average, as compared to 12.6 months for their peers in the chemotherapy cohort.
Merck learns from Keytruda's monotherapy miss in triple-negative breast cancer [Fierce Pharma] The thing is, none of Keytruda’s effects hit the statistical significance threshold. And the drug didn’t fend off disease progression, either.
Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy Showed Statistically Significant Increase in Pathological Complete Response Versus Chemotherapy as Neoadjuvant Therapy in Early-Stage Triple-Negative Breast Cancer (TNBC) [Merck] Interim Results from Pivotal Neoadjuvant/Adjuvant Phase 3 KEYNOTE-522 Trial Presented for the First Time at ESMO 2019 Congress During Presidential Symposium.
Merck's top cancer team basks in the warm light of positive Keytruda data from a landmark study for hard-to-treat breast cancer [EndPoints] The data aren’t mature enough to let Merck call it yet on events, but with the significantly higher rate of pCR running clearly in their favor, they believe they should be on track to scoring a win there as well.
Adding Pembrolizumab to Neoadjuvant Chemotherapy Improves Outcome in Early TNBC [ESMO] Neoadjuvant therapy with pembrolizumab plus chemotherapy provides greater anti-tumour activity than placebo plus chemotherapy in patients with early stage triple negative breast cancer.
	5.6.6.2 ESMO - SEIN (ABEMACICLIB)
Novartis, Lilly drugs set new survival bar in breast cancer [Biopharma Dive] Results from a Novartis trial, called MONALEESA-3, and another from Lilly, dubbed MONARCH-2, are the second and third time the drugs have been proven to help women with metastatic breast cancer that's hormone receptor positive, but HER2 negative, live longer.
Novartis Kisqali® delivers consistently superior overall survival – MONALEESA-3 trial demonstrates more life for postmenopausal HR+/HER2- advanced breast cancer patients [Novartis] Kisqali is the only CDK4/6 inhibitor to demonstrate positive overall survival in two pivotal Phase III trials -- consistently demonstrating approximately 30% reduction in the risk of death.
Verzenio® (abemaciclib) Significantly Extends Life by a Median of 9.4 Months for Women with HR+, HER2- Advanced Breast Cancer in MONARCH 2 Study [Lilly] Verzenio plus fulvestrant significantly extended life to a median of 46.7 months vs. 37.3 months compared to fulvestrant alone.
Novartis, Eli Lilly marquee positive survival data for CDK 4/6 franchises — but can they actually beat Pfizer's blockbuster? [EndPoints] "While CDK 4/6 inhibitors have now been in use for years “we are just beginning to understand which of these therapies meet the enormously important goal of significantly extending life in patients with advanced breast cancer.”
	5.6.7 ESMO - IMMUNOTHÉRAPIES
Gut Microbiota May Support an Immune Tolerant Profile That Affects Ipilimumab Activity [ESMO] Gut microbial metabolites may alter the activity of immune blockade agents.
	5.6.8 ESMO - CÔLON-RECTUM
Pfizer eyes commercial scale-up as Array colorectal cancer combo hits its marks [Fierce Pharma] The numbers have Pfizer “very excited” and planning an FDA submission for the fourth quarter of this year, Andy Schmeltz, global president and general manager of Pfizer’s oncology unit, said.
Pfizer Presents Interim Analysis Results from Phase 3 BEACON CRC Trial of BRAFTOVI® (Encorafenib), MEKTOVI® (Binimetinib) and Cetuximab for the Treatment of BRAFV600E-Mutant Metastatic Colorectal Cancer [Pfizer] Results to be presented during a late-breaking oral session at the 2019 ESMO Congress and simultaneously published in The New England Journal of Medicine.
Initial Results from MOUNTAINEER Trial Show Antitumor Activity of Tucatinib Combination in HER2-Positive Metastatic Colorectal Cancer [Seattle Genetics] Tucatinib is an oral, small molecule tyrosine kinase inhibitor that is highly selective for HER2.
Dual HER2 Blockade in Patients With HER2-Amplified Metastatic Colorectal Cancer [ESMO] TRIUMPH and MOUNTAINEER demonstrate promising clinical benefit for dual HER2 blockade in patients with HER2-amplified metastatic CRC; however, HERACLES-B did not meet the primary endpoint.