July 15, 2019 - 08:07 pm 0 Comments
OBR and MDoutlook are pleased to share excerpts from the most recent MDoutlook OncoPolls™ following this year’s ASCO annual meeting in Chicago. This final report (from series of three releases with MDoutlook over the past week) highlights the three (3) oral presentations from Tuesday morning ASCO presentations concerning chronic lymphocytic leukemia (CLL). These presentations discussed the first-line use of Venetoclax + Obinutuzumab, the use of Acalabrutinib + Obinutuzumab in both the first-line and relapsed/refractory settings, and the CAR-T product Lisocabtagene maraleucel.
This research is based on separate, identical surveys conducted with US and EU5-based oncologists who treat CLL. The full complimentary report is available through MDoutlook.
Abstract #7502: Venetoclax plus Obinutuzumab as a 1st line treatment for CLL
Key Conclusions about Abstract #7502 (Venetoclax + Obinutuzumab in first-line CLL)
Abstract #7500: Acalabrutinib plus Obinutuzumab for 1st line CLL and r/r CLL
Key Conclusions about Abstract #7500 (Acalabrutinib + Obinutuzumab in untreated and r/r CLL)
Abstract #7501: Lisocabtagene Maraleucel (Liso-Cel) in r/r CLL
Key Conclusions about Abstract #7501 (Liso Cel in r/r CLL)
Expected Integration of New ASCO Data into Clinical Practices
Key Conclusions about Integration of New ASCO Data into Clinical Practice
Overall Conclusions: Immediate Impact of 2019 ASCO Presentations on the Clinical Practice for CLL
Submitted by Robert Stephan, SVP, Research & Operations and Jan Heybroek, President, MDoutlook.
July 11, 2019 - 02:07 pm 0 Comments
OBR and MDoutlook are pleased to share more excerpts from the most recent MDoutlook OncoPolls™ following this year’s ASCO annual meeting in Chicago. This report highlights four (4) oral presentations concerning new targeted agents being developed against recognized driver mutations in metastatic non-small cell lung cancer (mNSCLC). These agents are: Capmatinib and Tepotinib (both targeting MET with exon 14 mutations), TAK-788 (targets specific EGFR mutations with exon 20 insertions), and BLU-667 (RET inhibitor).
This research is based on separate, identical surveys conducted with US and EU5-based treaters of mNSCLC. The full complimentary report is available through MDoutlook per details below.
Current Awareness and Evaluation of New Targeted Agents in mNSCLC
Key Conclusions around New Targeted Agents for mNSCLC
Comparison of New Targeted Agents for mNSCLC
Key Conclusions about Comparison of New Targeted Agents for mNSCLC
Overall Conclusions: Impact of 2019 ASCO Annual Meeting on Clinical Practice for mNSCLC with Driver Mutations
Submitted by: Robert Stephan, SVP, Research & Operations and Jan Heybroek, President MDoutlook.
July 08, 2019 - 03:07 pm 0 Comments
OBR and MD Outlook are pleased to share excerpts from the most recent MDoutlook’s OncoPolls™ from his year’s ASCO annual meeting in Chicago. This report highlights three presentations concerning the use of 2nd generation anti-androgens (2nd gen AAs) in the treatment of “early advanced” prostate cancer: non-metastatic, castration resistant prostate cancer (nmCRPC) and metastatic, hormone sensitive prostate cancer (mHSPC).
This research is based on separate, identical surveys conducted with US and EU5-based treaters of prostate cancer. The full complimentary report is available through MDoutlook per details below.
Abstract #5000: Darolutamide in nmCRPC
Key Conclusions about Abstract #5000 (Darolutamide in nmCRPC)
Abstracts #LBA2 & #5006:
Enzalutamide & Apalutamide in mHSPC
Key Conclusions about Abstracts #LBA2 & #5006 (Enzalutamide and Apalutamide in mHSPC)
Overall Conclusions: Immediate Impact of 2019 ASCO Presentations on the Clinical Practice for mHSPC and nmCRPC
Submitted by Robert Stephan, SVP, Research & Operations and Jan Heybroek, President MDoutlook.
June 04, 2019 - 05:06 pm 0 Comments
As the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting comes to an end, one of today’s final sessions included follow-up data from a phase 1b study of acalabrutinib and obinutuzumab in chronic lymphocytic leukemia (CLL), endpoint analyses of the phase 3 CLL-14 trial, and results of the phase 2 ORIENT-4 trial in NK/T cell lymphoma.
High and durable response rates with acalabrutinib plus obinutuzumab in CLL (Abstract 7500)
This open-label, phase 1b/2 trial (NCT02296918) evaluated acalabrutinib plus obinutuzumab in patients with treatment-naïve (n=19) or relapsed, refractory (n=26) CLL.
Primary endpoints were overall response rate (ORR) and safety. Minimal residual disease negativity (MRD–) was assessed at a sensitivity of 10-4. Common grade 3 and 4 adverse events (AE) included decreased neutrophil count (24%), syncope (11%), decreased platelet count, increased weight, and cellulitis (9% each). There were 2 (4%) grade 3 bleeding events and one (2%) grade 3 atrial fibrillation event.
With a median follow-up of about 3.5 years ORR was 95%, with 31.6% complete responses (CR) in the treatment-naïve patients and 92% with 7.7% CR in the relapsed, refractory patients. Neither median duration of response nor median progression-free survival (PFS) were reached in either group. MRD– in the bone marrow at day 1 of cycle 12 occurred in 26% of treatment-naïve patients and in 15% of those with relapsed refractory CLL.
Acalabrutinib plus obinutuzumab was well tolerated with no new safety signals and resulted in high response rates that were durable and deepened over time.
Fixed-duration venetoclax plus obinutuzumab induced MRD-negativity in previously treated CLL (Abstract 7502)
CLL-14, a phase 3, open-label trial (NCT02242942) compared fixed-duration venetoclax plus obinutuzumab to chloramabucil plus obinutuzumab in previously untreated patients with CLL and comorbidities typical of the CLL population, defined as a cumulative illness rating score (CIRS) >6 or an estimated creatinine clearance <70 mL/min. Patients were randomly assigned to 12 cycles of chlorambucil (n=216) or venetoclax (n=216) in combination with obinutuzumab for the first 6 cycles.
Progression-free survival (PFS) was the primary endpoint. MRD– in peripheral blood or bone marrow 3 months after end of treatment was a secondary endpoint. MRD– was analyzed every three months by an allele-specific polymerase chain reaction assay (ASO-PCR, cut-off 10-4) or by next generation sequencing (NGS, cut-offs 10-4, 10-5, 10-6).
At a median follow-up of 28 months, PFS was significantly longer in the venetoclax arm (88%) vs the chlorambucil arm (64%; HR 0.35; 95% CI 0.23-0.53; P<.0001). There was no difference in overall survival (OS) between arms.
MRD– by ASO-PCR was significantly higher in the venetoclax arm vs chlorambucil in both blood (76% vs 35%; P<.0001) and bone marrow (57% vs 17%; P<.0001) 3 months after treatment end. More patients in the venetoclax arm had MRD– in both blood and bone marrow (75% vs 49% in the chlorambucil arm), and a landmark analysis showed that MRD- in the blood was associated with longer PFS.
Higher, earlier, and more durable MRD– rates occurred in the venetoclax group; 81% had MRD negativity at 12 months after treatment end vs 27% in the chlorambucil arm (HR for MRD conversion 0.19; 95% CI 0.12-0.30; median time off treatment 18 months). MRD– by NGS was also higher in the venetoclax arm than in the chlorambucil arm (78% vs 34% at <10-4).
AE were similar between group; neutropenia was notable, and febrile neutropenia was low.
Fixed duration venetoclax plus obinutuzumab resulted in prolonged PFS associated with deep, high, and durable MRD– and low conversion to MRD positivity at one 1-year post-treatment in this patient population.
Sintilimab shows promise for relapsed, refractory extranodal NK/T cell lymphoma (Abstract 7504)
Sintilimab, an anti-PD-1 monoclonal antibody, was approved in China in 2018 to treat relapsed, refractory classical Hodgkin lymphoma. ORIENT-4, a single-arm, phase 2 trial (NCT03228836), evaluated the efficacy and safety of single agent sintilimab in relapsed, refractory extranodal NK/T cell lymphoma, which has a dismal prognosis after relapse, is more common in Asia than in North America and Europe, and has high levels of PD-L1 expression.
Patients (n=28) received sintilimab after failure of prior L-asparaginase and a median of 3 prior therapies. ORR was 67.9% with 7.1% CR, and disease control rate was 85.1%. The 1-year overall survival (OS) was 82.1%; median OS was not reached at a follow-up of 15.4 months, and 19 patients continue on study.
Grade 3 decreased lymphocyte count occurred in 2 patients; there were no grade 4 or 5 AE and no anti-drug antibodies. QoL significantly improved from baseline throughout the study.
Sintilimab was associated with early disease progression by PET in 5 patients who went on to experience CR (n=1) or partial response; this possible pseudoprogression requires further study.
By Lynne Lederman, PhD