Onco Actu du 1er juin 2020

	5.5.1 ASCO (GÉNÉRAL)
ASCO 2020 Highlights for Saturday [OBR] The gastrointestinal cancer session featured four studies, one of which was a phase 2/3 trial that compared donafenib to sorafenib in liver cancer. HER2CLIMB and MINDACT were both discussed during the breast cancer session. Although not discussed this morning, the results of PHERGAIN dropped at this meeting and offer a de-escalation strategy for patients with early breast cancer.
ASCO 2020 Highlights for Sunday [OBR] Sunday’s live broadcast of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting featured late-breaking data from a phase 3 trial evaluating early local therapy in metastatic breast cancer and the results of the phase 3 ENDURANCE trial.
New drugs make headway against lung, prostate, colon cancers [Medical XPress] A big drawback: It and other newer drugs are extremely expensive—$150,000 or more a year. How much patients end up paying depends on insurance, income and other factors.
	5.5.1.1 ASCO (GÉNÉRAL) - INDUSTRIELS
AstraZeneca, Daiichi niche drug shows promise beyond breast cancer [Reuters] Drugmakers are increasingly using biomarker-driven drugs to treat patients with rare tumours, and AstraZeneca made a $7-billion bet on the treatment when it partnered with Japan’s Daiichi last year to work on the drug in a direct challenge to Roche.
	5.5.10 ASCO (HÉMATO)
Takeda Announces Compelling Data from the Phase 2 Trial of Pevonedistat Plus Azacitidine in Patients with Higher-Risk MDS [Takeda] Pevonedistat Combination Demonstrates the Potential to Double Complete Remissions and Improve Outcomes in HR-MDS, With Safety Profile Similar to Azacitidine Alone.
Takeda to Present Data from the ICLUSIG® (ponatinib) Clinical Trial Program that Could Prove Practice-Changing for the Treatment of Chronic-Phase CML [Takeda] Findings Support Response-Based Dosing Regimens of ICLUSIG Can Optimize Benefit-Risk Profile in Patients with Resistant / Intolerant Chronic-Phase CML.
After starring at ASH last fall, Gilead’s new Forty Seven crew colors in more promising data for magrolimab at ASCO [EndPoints] Researchers have data on 68 patients who have been treated with magrolimab plus azacitidine in a single arm study involving cases of untreated higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia.
MTX-based Chemotherapy Combined with Low-Dose, Whole-Brain Radiotherapy Improves Progression-free Survival for Patients with Newly Diagnosed CNS Lymphoma [NRG Oncology] The study met its primary endpoint of demonstrating the improvements in progression-free survival. However, investigators cautioned that further neuropsychological testing and neuroimaging analyses are still ongoing to fully characterize cognitive decline associated with this treatment.
	5.5.11 ASCO (SNC]
ASCO: Ziopharm's IL-12 gene therapy boosts survival in hard-to-treat brain cancer [Fierce Biotech] The company tested the treatment, dubbed Controlled IL-12, in 95 patients as a monotherapy in two studies and in combination with a PD-1 inhibitor in a third study.
Ziopharm Oncology Presents Encouraging Clinical Data for Controlled IL-12 for the Treatment of Recurrent Glioblastoma at the 2020 American Society of Clinical Oncology [Ziopharma] Controlled IL-12 in combination with PD-1 inhibitor has favorable safety profile and initial survival data are encouraging.
Early survival data boost Ziopharm's 'controlled IL-12' immunotherapy for glioblastoma [EndPoints] On top of boosting its case as a monotherapy, the data can also bode well for a combination with Regeneron’s PD-1 inhibitor, Libtayo.
	5.5.15 ASCO (BIOPSIES LIQUIDES)
Lucence Dx Liquid Biopsy Tech Detects Structural Rearrangements, Breast Cancer Mutations [Genome Web] Lucence believes the studies support the clinical utility of using AmpliMark for detecting actionable mutations in the different cancer types, allowing for faster and more accurate testing than current approaches.
Oncologists Make Progress Toward Showing Utility for Brain Cancer Liquid Biopsy [Genome Web] Brain cancers have emerged as somewhat of a conundrum for the liquid biopsy field, providing both a clear opportunity — because of the difficulty and danger in obtaining tissue samples from the brain relative to other organs — but also a significant challenge, as research has shown that brain tumors seem to shed DNA into the blood at much lower rates and quantities than other cancers.
	5.5.16 ASCO (MÉDECINE DE PRÉCISION)
Pediatric Precision Oncology Study Matches 28 Percent of Patients to Targeted Therapies [Genome Web] Doctors from 72 sites in eight European countries submitted fresh, frozen tumor and blood for germline analysis from their patients with refractory, relapsed, progressive malignant disease for the study, van Tilburg said, noting that cases who were at exceptionally high risk at primary diagnosis could also participate in the study.
Germline Results From Tumor-Normal Sequencing Guides Precision Therapy in Advanced Cancer Patients [Genome Web] In one study, involving 12,000 patients treated at Memorial Sloan Kettering Cancer Center, researchers identified nearly 600 patients with recurrent or metastatic cancer who had actionable germline mutations, and 44 percent of them received targeted drugs either as part of the standard of care or as part of a research protocol.
Efficacy of Vitrakvi™ (larotrectinib) further established with continued high response rates and durable response in updated analyses in adult patients and quality of life data in adult and pediatric patients with TRK fusion cancer [Bayer] 71% overall response rate (ORR) per investigator assessment and median duration of response of 35.2 months shown in expanded data set of 116 adult patients with TRK fusion cancer.
TAPUR Study Shows Encouraging Results for Olaparib in BRCA-Mutated Advanced Prostate and Pancreatic Cancers [ASCO] In two small cohorts, olaparib treatment resulted in objective responses or stable disease for at least 16 weeks in more than two-thirds (68%) of patients with advanced prostate cancer and BRCA1/2 inactivating mutations, and nearly a third (31%) of patients with advanced pancreatic cancer and BRCA1/2 inactivating mutations.
Targeted therapy pralsetinib achieves high response rates in advanced cancers with RET gene fusions [MD Anderson Cancer Center] MD Anderson-led Phase I/II ARROW trial finds RET inhibitor to be well-tolerated with durable antitumor activity.
	5.5.16.2 ASCO (MÉDECINE DE PRÉCISION-SEIN)
Myriad Presents New Data at ASCO Validating the Ability of riskScore® to Provide Personalized Breast Cancer Risk Information to Patients [Myriad] “The validation data we are presenting at ASCO this year will support a broader launch of riskScore to even more women in the coming year with more personalized information and the unique ability to modify carrier risk through a clinically validated tool.”
Polygenic Risk Score, Family History Refine Breast Cancer Risk Assessment in CHEK2 Mutation Carriers [Genome Web] Overall, pathogenic CHEK2 mutations are thought to coincide with a moderate risk of breast cancer — in the 23 to 28 percent lifetime risk range — he explained, though that risk appears to be dialed up or down depending on broader genetic risk factors, an individual's family history, and certain environmental exposures.
Oncotype DX May Be Helpful in Guiding Neoadjuvant Breast Cancer Treatment Decisions [Genome Web] Given these updated guidelines, as well as the data from the three new ASCO studies, Shak believes there will be an "expanded use of the recurrence score in the [neoadjuvant] setting so that patients can get the right treatment before surgery."
Exact Sciences Showcases Continued Progress In Cancer Diagnostics At ASCO 2020 [Exact Sciences] New data and society guidelines support value of Oncotype DX Breast Recurrence Score® test in guiding neoadjuvant treatment decisions for newly diagnosed patients.
	5.5.16.3 ASCO (MÉDECINE DE PRÉCISION-KRAS, HRAS)
Kura flashes positive HRAS data on once-failed J&J drug [EndPoints] Now for the first time in the 15-plus year history of the compound, Kura has evidence that, when given to the right patients, the drug can help patients live longer.
Kura Oncology Reports Overall Survival Data from Phase 2 Trial of Tipifarnib in HRAS Mutant Head and Neck Squamous Cell Carcinoma[Kura] Median OS of 15.4 months, median PFS of 5.9 months and ORR of 50% observed in recurrent/metastatic HRAS mutant HNSCC.
	5.5.2 ASCO (SEIN)
Trastuzumab Achieves Slight Reduction in Recurrence for Women with HER2-Positive Ductal Carcinoma in Situ on NRG Oncology Trial NSABP B-43 [NRG Oncology] The addition of the monoclonal antibody therapy Trastuzumab to radiotherapy did not reach the protocol objective of a 36% reduction in the ipsilateral breast tumor recurrence rate for women with HER2-positive ductal carcinoma in situ (DCIS) on the NRG Oncology clinical trial NSABP B-43.
	5.5.3 ASCO (PROSTATE)
Final PROSPER Results Show XTANDI® (enzalutamide) Significantly Extends Overall Survival in Men with Non-Metastatic Castration-Resistant Prostate Cancer [Astellas] The median OS was 67.0 months (95% CI: 64.0 to not reached) for men who received XTANDI plus ADT compared to 56.3 months (95% CI: 54.4 to 63.0) with placebo plus ADT. OS was a key secondary endpoint of the trial.
Myovant’s relugolix wins a pivotal prostate cancer showdown with an old standard — coming down to the wire on approvals [EndPoints] In this new data from Myovant, developers highlighted clearly superior results for the biotech’s drug over an old standard leuprolide (sold as Lupron), ringing three bells on efficacy, safety and quality of life.
Myovant Sciences Announces Additional Positive Efficacy and Cardiovascular Safety Data from Phase 3 HERO Study of Once-Daily, Oral Relugolix in Advanced Prostate Cancer and Publication in the New England Journal of Medicine [Myovant] Presentation expands on previous results demonstrating superiority of relugolix to leuprolide acetate, with additional data on testosterone suppression and recovery, prostate-specific antigen (PSA) response, and cardiovascular safety.
	5.5.4.1 ASCO (IMMUNOTHÉRAPIES-REIN)
Study reveals factors influencing outcomes in advanced kidney cancer treated with immunotherapy [Dana Farber Cancer Institute] The study showed that features that are typically linked to immunotherapy response or resistance in other types of cancer don’t work the same way in advanced clear cell renal cell cancer (ccRCC).
	5.5.4.2 ASCO (IMMUNOTHÉRAPIES-COMBINAISONS)
ASCO: Merck, Eisai pad case for liver cancer nod with Keytruda-Lenvima combo data [Fierce Pharma] While the trial, called Keynote-524, is a single-arm, phase 1b study, it’s already helped the duo nab a breakthrough therapy designation from the FDA.
ASCO: Has AstraZeneca finally found a place for long-plagued I-O candidate tremelimumab? [Fierce Pharma] The performance may bode well for AstraZeneca’s phase 3 Himalaya study, set to read out in the second half of this year, where the British drugmaker is hoping its duo can replicate its success, this time in previously untreated patients—a group that has over the years proved difficult to treat.
Imfinzi plus tremelimumab demonstrated promising clinical activity and tolerability in patients with advanced liver cancer [AstraZeneca] Data presented at ASCO showed patients treated with a single, priming dose of tremelimumab plus Imfinzi achieved longest median survival among regimens tested.
	5.5.4.4 ASCO (IMMUNOTHÉRAPIES-POUMON)
As tislelizumab gains traction in China, BeiGene pulls the curtain on NSCLC data supporting the PD-1 drug [EndPoints] The 360-patient trial, which tested the checkpoint inhibitor with two different chemo regimens against chemo alone, showed that the median time during which patients did not see disease progression in the tislelizumab combo groups was 7.6 months versus 5.5 months for chemo alone.
	5.5.4.5 ASCO (IMMUNOTHÉRAPIES-CAR-T, THÉRAPIES CELLULAIRES)
Allogene Therapeutics, with Collaborator Servier, Reports Positive Results from its Phase 1 ALPHA Study of ALLO-501 in Relapsed/Refractory Non-Hodgkin Lymphoma at the American Society of Clinical Oncology Annual Meeting [Allogene] In the Ongoing Study, 22 Patients were Evaluable for Safety and 19 Patients Were Evaluable for Efficacy with at Least One Tumor Assessment as of Data Cutoff.
Headed to PhII: Allogene CEO David Chang completes a positive early snapshot of their off-the-shelf CAR-T pioneer [EndPoints] 9 of the 12 responders remained in response at the data cutoff, offering a glimpse on durability that still has a long way to go before it can be completely nailed down.
Adoptive T-cell therapy ADP-A2M4 targeting MAGE-A4 shows early activity in patients with advanced solid tumors [MD Anderson Cancer Center] MD Anderson-led Phase I trial of Adaptimmune T-cell receptor therapy sees confirmed responses in multiple cancer types.
	5.5.4.6 ASCO (IMMUNOTHÉRAPIES-PEAU, MÉLANOME)
Libtayo® (cemiplimab-rwlc) longer-term results in advanced cutaneous squamous cell carcinoma presented at ASCO 2020 show durable responses that deepen over time [Sanofi] Across all groups combined, complete responses (CR) are now 16%; in the metastatic group with the longest follow-up, CRs are 20% representing a 200% increase over two years.
	5.5.4.7 ASCO (IMMUNOTHÉRAPIES- GASTRO-INTESTINAL)
Immunotherapy proves effective for the first time as a sole treatment for a subtype of metastatic colorectal cancer [VHIO] It is the first time a treatment using only the anti-PD1 antibody pembrolizumab and not including chemotherapy has proved effective as a first-line treatment in patients with colorectal cancer with microsatellite instability.
Immunotherapy for bowel cancer could change clinical practice [University College London] For patients treated with pembrolizumab, progression-free survival was 55.3% at 12 months and 48.3% at 24 months. This compared with 37.3% and 18.6% respectively, for those on chemotherapy.
	5.5.5 ASCO (GASTRO-INTESTINAL)
Enhertu significantly improved tumour response rate and overall survival in HER2-positive metastatic gastric cancer in Phase II DESTINY-Gastric01 trial [AstraZeneca] First HER2-directed medicine to show an improvement in overall survival for previously treated metastatic gastric cancer with a 41% reduction in the risk of death vs. chemotherapy.
Enhertu achieved a tumour response rate of 45.3% in patients with HER2-positive metastatic colorectal cancer in Phase II DESTINY-CRC01 trial [AstraZeneca] The primary endpoint of confirmed objective response rate (ORR), assessed by independent central review, showed 45.3% of patients with HER2-positive (defined as IHC3+ or IHC2+/ISH+) advanced colorectal cancer treated with Enhertu (trastuzumab deruxtecan) monotherapy (6.4mg/kg) achieved a tumour response.
AstraZeneca’s $7B ADC succeeds where Roche failed, improving survival in gastric cancer [EndPoints] The positive results are particularly noteworthy because a key rival drug failed against gastric cancer. Kadcyla, Roche’s blockbuster HER2 targeting antibody drug conjugate, flopped 5 years ago in a Phase II/III trial in second-line patients.
Trastuzumab Combined with Trimodality Treatment Does Not Improve Outcomes for Patients with HER2-Overexpressing Esophageal Cancer on NRG Oncology Trial [NRG Oncology] The Phase III NRG-RTOG 1010 trial evaluated 203 HER2 positive patients with a median follow up of 5 years.
	5.5.6 ASCO (PEAU-MÉLANOME)
Novartis announces long-term, relapse-free survival benefit for high-risk, stage III melanoma patients treated with Tafinlar® + Mekinist® following surgery [Novartis] Study conclusions are drawn from the largest dataset and longest follow-up to date of patients with BRAF-mutated melanoma treated with targeted therapy following the surgical removal of their cancer.
	5.5.7 ASCO (GYNÉCO)
Combined Cediranib and Olaparib Presents Similar Activity to Standard of Care Treatment for Platinum-Sensitive Ovarian Cancer [NRG Oncology] There were no overall survival differences between the treatment arms. Patients who received cediranib and olaparib in addition to the standard of care did experience a higher frequency of grade 3 or higher gastrointestinal, hypertension, and fatigue adverse events.
	5.5.8 ASCO (POUMON)
Enhertu demonstrated meaningful clinical activity in patients with HER2-mutant non-small cell lung cancer in interim analysis of Phase II DESTINY-Lung01 trial [AstraZeneca] 61.9% of patients with HER2-mutant metastatic non-small cell lung cancer treated with Enhertu achieved a tumour response.
Targeted therapy tepotinib for non-small cell lung cancer with MET exon 14 skipping mutation shows durable response [MD Anderson Cancer Center] Phase II clinical trial shows 46.5% objective response rate.
Study shows comprehensive genomic profiling identified co-occurring alterations that may cause treatment resistance in patients with METex14-altered non-small cell lung cancer [Dan Farber Cancer Insitute] Alterations that cause skipping of exon 14 on the MET gene (METex14) are drivers of a type of lung cancer with a poor prognosis, but that is treatable with a recently approved MET inhibitor.
	5.5.9 ASCO (AUTRES ORGANES)
Pfizer, Merck KGaA cement Bavencio bladder cancer win with OS data — while carving another niche in rare cancer [EndPoints] All 700 patients in the trial completed chemotherapy before getting randomized to either maintenance therapy with Bavencio or regular checking. Those on the drug arm saw mOS of 21.4 months, compared with 14.3 months on the comparator group.