The OBR Blog

July 15, 2019 - 08:07 pm comments0 Comments

Introduction

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.

OncoPoll™ Methodology

  • Primary research surveys were sent to verified and validated oncologists with an identified clinical interest in CLL and other B-cell lymphomas utilizing targeting parameters within the proprietary MDoutlook®global cancer treater and expert panel
  • Timing: June 2019. Launched shortly after close of 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL., May 31-June 4, 2019
  • Fielding via interactive web-based survey instruments, utilizing proven MDoutlook methodology and proprietary technology
  • Links to discussed abstracts on the ASCO website were provided within the survey
  • Responses: 100 total, 50 US and 50 EU5 oncologists. Overall, 51 respondents were at academic centers (16 US | 35 EU5) and 49 community-based practitioners (34 US | 15 EU5)

Abstract #7502: Venetoclax plus Obinutuzumab as a 1st line treatment for CLL

Key Conclusions about Abstract #7502 (Venetoclax + Obinutuzumab in first-line CLL)

  • Moderately high level of awareness about this presentation, especially among academics
    • Overall, only 9% of respondents had no awareness about this Abstract
  • After reviewing the abstract, respondents perceive a high improvement in efficacy of this regimen compared to other currently available treatments
    • The safety & tolerability and the administration / dosing schedule (fixed duration treatment) are also seen as advantages for this regimen
      • Although some concern was expressed by European community oncologists over the safety & tolerability issues

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)

  • A moderate level of awareness about this Abstract is present, more in academics than community and slightly higher in EU5 than in US
  • Remarkable consistency in the ratings of the efficacy and safety & tolerability profiles for this regimen in both the front line and relapsed / refractory setting
    • Efficacy ratings are slightly better than the safety & tolerability ones
    • Overall, the ratings are pretty consistent between US and EU5 oncologists

Abstract #7501: Lisocabtagene Maraleucel (Liso-Cel) in r/r CLL

Key Conclusions about Abstract #7501 (Liso Cel in r/r CLL)

  • As with Abstract #7500, a moderate level of awareness about this Abstract is present, more in academics than community and slightly higher in EU5 than in US
  • In terms of the efficacy outcomes, this CAR-T cell treatment has an even higher level of excitement than Acalabrutinib + Obinutuzumab in the r/r setting
    • Even with the potential toxicities seen with on the CAR-T cell approaches, the safety & tolerability of Liso Cel in this setting appears to be no worse / slightly better than other currently available approaches

Expected Integration of New ASCO Data into Clinical Practices

Key Conclusions about Integration of New ASCO Data into Clinical Practice

  • None of these 3 treatment regimens are regularly used in CLL (Venetoclax + Rituximab and Acalabrutinib alone are) (see the full MDoutlook report for current treatment details)
  • For future 1stline treatments:
    • Even with the strength of the new data presented, just over half (54%) of all treatment decisions will stay the same as today
    • While Obinutuzumab with either Acalabrutinib or Venetoclax will be used as an initial treatment, U S oncologists will favor using Acalabrutinib while EU oncologists will favor using Venetoclax
  • For future 2ndline treatments:
    • These three regimens are expected to comprise the majority of 2ndline treatments, especially in academic settings
    • Academics in both the US and EU will integrate Liso Cel as early as the 2ndline, at least in selected patients (up to 20%)
  • For future 3rdline treatments:
    • As with the 2ndline, most (57%) of treatments are expected to involve one of these three regimens
    • Liso Cel will be the top treatment in the 3rdline, with community-based oncologists willing to refer for it if the CLL patient progresses this far

Overall Conclusions: Immediate Impact of 2019 ASCO Presentations on the Clinical Practice for CLL

  • Even though the CLL Oral Abstract presentations were not until the very end of ASCO, it did not appear to dampen the awareness or enthusiasm for these presentations
    • EHA (European Hematology Association annual congress, Amsterdam 14thto 16thJune 2019) following 2 weeks later as a “reinforcement” / expansion of new data probably helped contribute to this
  • Acalabrutinib + Obinutuzumab, Venetoclax + Obinutuzumab, and the CD19-targeted CAR-T cell product Liso Cel are all positively viewed and eagerly awaited as standard treatment options for patients with CLL
  • Identification of specific patient populations for these and current treatment regimens, including older ones like FCR, and a better understand of the optimal sequencing of these various treatment regimens is needed

For a more detailed analysis report, please click here to visit MDoutlook or click here to obtain this report.

Submitted by Robert Stephan, SVP, Research & Operations and Jan Heybroek, President, MDoutlook.

July 11, 2019 - 02:07 pm comments0 Comments

Introduction

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.

OncoPoll™ Methodology

  • Primary research surveys were sent to verified and validated oncologists with an identified clinical interest in lung cancers utilizing targeting parameters within the proprietary MDoutlook®global cancer treater panel
  • Timing: June 2019. Launched shortly after close of 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL., May 31-June 4, 2019
  • Fielding via interactive web-based survey instruments, utilizing proven MDoutlook methodology and proprietary technology
  • Links to discussed abstracts on the ASCO website were provided within the survey
  • Responses: 101 total, 50 oncologists in US and 51 oncologists EU5

Current Awareness and Evaluation of New Targeted Agents in mNSCLC

Key Conclusions around New Targeted Agents for mNSCLC

  • Overall level of awareness about each of these agents is already moderate, even though all presentations were relatively early Ph1 – Ph2 trials
    • Roughly 25-40% of respondents had no awareness about each of these agents [links to Abstracts were provided after measuring awareness so evaluation could be done by all]
    • Europeans are more aware of these agents than American oncologists, even though attendance at the mNSCLC Oral abstract session was similar (see full report for details)
  • After reviewing the abstract, the respondents believe all of these agents have a better efficacy potential and safety profile than currently available options for these relevant patient subgroups
    • Fewer than 3% think any of these agents have a worse efficacy profile than currently available options, while 7% believe any’s side effects are worse than currently available treatments
    • Overall, the ratings are very consistent between US and EU5 oncologists

Comparison of New Targeted Agents for mNSCLC

Key Conclusions about Comparison of New Targeted Agents for mNSCLC

  • We asked the respondents to rank the 4 agents as to their likely greatest impact on their NSCLC practices
  • Each of these 4 drugs had their fans (selected most important) and detractors (selected least important)
  • US and EU5 oncologists are divided on which agents will have biggest impact on their practices
    • US #1 ranking (Tepotinib) is driven by having the most oncologists rank it as the most important, while the #1 in EU5 (Capmatinib) is driven by having fewest rank it as least impactful (and over 50% ranking it their #2)
  • Directly comparing the rankings for the 2 MET inhibitors, Tepotinib has more fans in both the US and EU5, but it also has more detractors than Capmatinib
    • Overall, US ranks Tepotinib higher while EU5 oncologists rank Capmatinib better

Overall Conclusions: Impact of 2019 ASCO Annual Meeting on Clinical Practice for mNSCLC with Driver Mutations

  • A number of new targeted therapies are in clinical development for specific mutational populations in mNSCLC. Even though the clinical studies are somewhat early, oncologists are beginning to take notice of these agents
  • All of these agents are seen as having better efficacy and an improved safety profile when compared to the currently available options for these subgroups of patients
  • As their clinical development continues and the results mature, oncologists will likely be quick to integrate these agents as they obtain regulatory approval and commercial availability in their countries. This will impact both the current treatments used for these patients and the testing for these specific genetic alterations (see our full report for more details around current genetic testing practices)

For a more detailed analysis report, please click here to visit MDoutlook or click here to view this report.

Submitted by: Robert Stephan, SVP, Research & Operations and Jan Heybroek, President MDoutlook.

 

 

July 08, 2019 - 03:07 pm comments0 Comments

Introduction

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.

OncoPoll™ Methodology

  • Primary research phase involved surveys to verified and validated oncologists and urologists with an identified clinical interest in prostate cancer utilizing targeting parameters within the proprietary MDoutlook®global cancer treater panel
  • Timing: June 2019. Launched shortly after close of 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL., May 31-June 4, 2019
  • Fielding via interactive web-based survey instruments, utilizing proven MDoutlook methodology and proprietary technology
  • Links to discussed abstracts on the ASCO website were provided within the survey
  • Responses: 108 total, 73 oncologists (37 US | 36 EU5) and 35 urologists (15 US | 20 EU5)

Abstract #5000: Darolutamide in nmCRPC

Key Conclusions about Abstract #5000 (Darolutamide in nmCRPC)

  • Overall level of awareness about this abstract is still only moderate
    • Calculated average of 2.23 on 0 to 5 scale
    • As anticipated, awareness is higher among oncologists than urologists
    • Interestingly, Europeans are more aware of this presentation than Americans
  • After reviewing the abstract, the respondents believe Darolutamide has a better efficacy and safety profile than currently available options for nmCRPC
  • Upon regulatory approval and commercial availability, there will be some immediate integration of Darolutamide into the treatment practices for nmCRPC
    • Overall, 12-15% of nmCRPC patients will be treated with Darolutamide, with varying percentages based on the type of physician treating and geography (ranging from 8-21% of total patients)
    • More physicians in Europe will use Darolutamide in their nmCRPC practices (46% vs. 26% of US physicians), with the US oncologists being the population least likely to use it (only 20% will use in at least 1 patient) (data not shown)

Abstracts #LBA2 & #5006:
Enzalutamide & Apalutamide in mHSPC

Key Conclusions about Abstracts #LBA2 & #5006 (Enzalutamide and Apalutamide in mHSPC)

  • Similar moderately high level of awareness about both of these abstracts, with slightly higher awareness by oncologists over urologists, and Europeans over Americans
  • After reviewing the abstract, even though #LBA2 about Enzalutamide was presented during the Plenary Session, the Apalutamide Oral Abstract was actually thought to have a small edge in both efficacy and safety & tolerability
  • There will be an increased usage of both Enzalutamide and Apalutamide in the mHSPC setting expected to increase, distinct preferences are seen by specialty and regionality

Overall Conclusions: Immediate Impact of 2019 ASCO Presentations on the Clinical Practice for mHSPC and nmCRPC

  • This year was a banner year for prostate cancer, with 3 major presentations concerning 2ndgen AAs in the treatment of nmCRPC and mHSPC
    • As seen with the similar level of awareness between #LBA2 and #5006, the interest and newsworthy results from related presentations likely drives coordinate learning
  • The 2ndgen AAs are becoming (if not already) the standards of care for the mHSPC and nmCRPC populations of prostate cancer patients. The use of ADT alone will likely be only for early / localized disease while chemotherapy will move back to the last lines of treatment (in mCRPC)
  • Competition among the 2ndgen AAs is likely only going to get more intense with the 4th(Darolutamide) expected to soon receive its commercial authorization. Additional studies will be needed to clearly differentiate these agents from each other and identify the specific patient population(s) best suited for each one

For a more detailed analysis report, personalized to suit your informational needs, please click here to visit MDoutlook or click here to view this report.

Submitted by Robert Stephan, SVP, Research & Operations and Jan Heybroek, President MDoutlook.

June 04, 2019 - 05:06 pm comments0 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

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