Introduction

In an effort to provide you with timely market feedback from the 2016 ASCO Annual Meeting, OBR and MDoutlook are pleased to share results from MDoutlook’s OncoPolls™ conducted immediately after the meeting. This report explores skin cancer (melanoma and merkel cell carcinoma) presentations concerning the use of checkpoint inhibitors and the combination of BRAF and MEK inhibitors.

OncoPoll™ Methodology

• Primary research phase involved a global survey to verified and validated medical oncologists and multi-disciplinary physicians with an identified clinical interest in genitourinary cancers utilizing targeting parameters within the proprietary MDoutlook^® global cancer treater panel
• Timing: June 2016. Launched 1 day after close of 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL, June 3-7, 2016
• Fielding to proprietary panel of cancer treaters, targeted by clinical interest
• Data capture via interactive web-based survey instrument, utilizing proven MDoutlook methodology and proprietary technology
• Links to discussed abstracts on the ASCO website were provided within the survey
• Reponses at data collection: 90
• Responses are from 14 countries: Austria, Belgium, Brazil, Canada, France, Germany, Hungary, Italy, Romania, Spain, Sweden, Switzerland, United Kingdom and US

Key Conclusions

• On a 0 – 5 scale of 0 = no awareness to 5 = very aware, clinicians have an above average awareness of these presentations
  • A slightly higher level of awareness is seen by those outside of the US
  • Attendees of the conference showed a higher level of awareness (not shown)
  • The awareness about avelumab in merkel cell carcinoma was somewhat lacking compared to the other antibodies in melanoma
• Clinical impact, also rated on a 0 – 5 scale of 0 = no impact at all to 5 = very important, for these agents in general are seen as very clinically meaningful
  • US oncologists rate the merkel cell abstract as less clinically important
  • For most of these abstracts, importance assigned is slightly higher by those who did not attend the meeting, although the differences are never very large

Key Conclusions

• On the same 0 – 5 scale, there is an above average level awareness about this presentation outside of the US, while awareness in the US is slightly lower
  • Higher level of awareness among the attendees compared to those who did not attend (not shown)
• Oncologists view this as an important presentation, with those outside the US rating it as very clinically important
  • Attendance at the meeting does not impact the rating of clinical importance (not shown)
• Oncologists view this as an important presentation, with those outside the US rating it as very clinically important
  • Attendance at the meeting does not impact the rating of clinical importance (not shown)
  • Even with the clinical importance of this abstract, expected usage of the BRAF + MEK inhibitor combination as 1^st line therapy for BRAF V600E/K-mutant melanoma is expected to loose favor to the use of checkpoint inhibitors (not shown)

Conclusions: Immediate Impact of 2016 ASCO Presentations on Clinical Practice for Melanoma and Merkel Cell Carcinoma

• All of these studies highlight the importance of the ASCO Annual Meeting to the entire global oncology community – awareness of these presentations are high and can occur quite quickly even for those who did not attend
• The importance of these presentations suggest that integration of these results into clinical practice will happen in relatively short order, especially since most of these agents are already widely available and in use

For a more detailed analysis report, please click here to download the full report.

Submitted by Robert Stephan, VP, Research and Physician Society, and Jan Heybroek, President MDoutlook.

Introduction

In an effort to provide you with timely market feedback from the 2016 ASCO Annual Meeting, OBR and MDoutlook are pleased to share results from MDoutlook’s OncoPolls™ conducted immediately after the meeting. This report explores genitourinary (non-prostate) presentations concerning the use of checkpoint inhibitors as therapy for bladder cancer and new overall survival data for agents in kidney cancer.

OncoPoll™ Methodology

• Primary research phase involved a global survey to verified and validated medical oncologists and multi-disciplinary physicians with an identified clinical interest in genitourinary cancers utilizing targeting parameters within the proprietary MDoutlook^® global cancer treater panel
• Timing: June 2016. Launched 4 days after close of 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL, June 3-7, 2016
• Fielding to proprietary panel of cancer treaters, targeted by clinical interest
• Data capture via interactive web-based survey instrument, utilizing proven MDoutlook methodology and proprietary technology
• Links to discussed abstracts on the ASCO website were provided within the survey
• Reponses at data collection: 89
• Responses are from 20 countries: Argentina, Austria, Belgium, Brazil, Canada, Chile, France, Germany, Israel, Italy, Netherlands, Norway, Pakistan, Poland, South Africa, Spain, Sweden, Turkey, United Kingdom and US

Key Conclusions

• On a 0 – 5 scale of 0 = no awareness to 5 = very aware, clinicians have an above average awareness of these presentations
  • A general higher level of awareness is seen by those in the US (~0.5-0.7 higher ratings)
  • The awareness about durvalumab was somewhat lacking compared to the other antibodies
• Clinical impact, also rated on a 0 – 5 scale of 0 = no impact at all to 5 = very important, for these agents in general are seen as very clinically meaningful
  • US oncologists assign a higher importance to these agents than those outside of the US
  • In total, a slightly higher level of importance is seen for 2^nd+ line than in 1^st line
  • Both awareness and assigned importance is greater for those who attended the meeting than those who did not (not shown)
• In a follow-up question, we asked if participants had used atezolizumab for urinary cancer in their practices yet (outside of clinical trials); 40% of US respondents say they had, compared to 11% of those outside of the US

Key Conclusions

• On the same 0 – 5 scale, there is an above average level awareness about these presentations in the US, while awareness outside of the US is about average
  • No meaningful differences in awareness between these two abstracts
  • Much higher level of awareness among the attendees (3.8-3.9) compared to those who did not attend (2.7-2.8)
• US oncologists view both of these presentations as very clinically important. Those outside of the US view these as less important and the nivolumab data as more important than the Meteor data
  • More importance (over a full point difference) was assigned to both presentations by the attendees than with the non-attendees (not shown)

Conclusions: Immediate Impact of 2016 ASCO Presentations on Clinical Practice for Bladder and Kidney Cancer

• All of these studies highlight the importance of the ASCO Annual Meeting to the entire global oncology community – awareness of these presentations are high and can occur quite quickly even for those who did not attend
• The importance of these presentations suggest that integration of these results into clinical practice will happen in relatively short order, especially since most of these agents are already widely available and in use

For a more detailed analysis report, please click here to download the full report.

Submitted by Robert Stephan, VP, Research and Physician Society, and Jan Heybroek, President MDoutlook.

By Gena Kanas, M.P.H., Ph.D., Consultant, Clinical & Scientific Assessment, Kantar Health

At ASCO 2016, new data was presented on potential biomarkers that could predict response to immunotherapy in the treatment of a variety of cancers. Current U.S. Food and Drug Administration (FDA)-approved PD-1/-L1 checkpoint inhibitor immunotherapy approvals include the use of Keytruda® (pembrolizumab, Merck & Co.) or Opdivo® (nivolumab, Bristol Myers-Squibb/Ono Pharmaceuticals) in advanced melanoma and advanced non-small cell lung cancer (NSCLC); Opdivo for use in advanced renal cell carcinoma and Hodgkin’s lymphoma; and most recently approved Tecentriq™ (atezolizumab, Genentech/Roche) in advanced urothelial carcinoma.

One goal for the choice of biomarkers is their utility to select only those patients who will respond to a given treatment. Current immunotherapies target the interaction between PD-1 and PD-L1, and the inhibition of this interaction leads to antitumor activity. Unfortunately, over half of patients treated with immunotherapy do not show a clinical response, which has led to further investigation into possible immunotherapy combination strategies and to identify potential biomarkers to better predict those patients who best respond to immunotherapy.

The use of tumor mutation burden, mismatch repair deficiency and PD-L1 expression as possible biomarkers were discussed at this year’s ASCO conference.

PD-L1 Expression

Two abstracts from the KEYNOTE-010 and KEYNOTE-021 studies focused on PD-L1 expression as a potential predictive biomarker for response in NSCLC patients. KEYNOTE-010 reported a general correlation between improved efficacy with increasing PD-L1 expression, as defined by a tumor proportion score (TPS), in Keytruda-treated NSCLC patients compared to docetaxel.¹ However, since PD-L1-negative patients were not included in the study, KEYNOTE-010 was unable to evaluate PD-L1 status as a biomarker for Keytruda. KEYNOTE-021 reported improved efficacy of Keytruda combined with different chemotherapy regimens regardless of PD-L1 status in three cohorts of advanced NSCLC patients .² Across all three cohorts, the overall response rate (ORR) did not significantly differ between patients with TPS of 1% or greater and those with TPS less than 1%. These studies suggest that PD-L1 expression is weakly correlated with clinical response to immunotherapy.

Tumor Mutation Burden

Three abstracts reported on tumor mutation burden (TMB) as a possible predictor of immunotherapy response in NSCLC, melanoma, and urothelial carcinoma patients. Each study used the same set of genes for the analysis of TMB (calculated as the number of synonymous and nonsynonymous variants from a series of 236-315 genes).

The first study reported a correlation between TMB and longer immunotherapy (Keytruda, Opdivo, or avelumab (Pfizer)) treatment duration in 64 NSCLC cases.³ Patients with TMB of 15 mutations/Mb or more had a longer immunotherapy treatment duration compared to those with TMB of less than 15 mutations/Mb (p=0.010). However, the authors did not report data on efficacy of immunotherapy treatment by level of TMB.

The authors of the second analysis reported a correlation between increasing TMB and higher progression free survival (p<0.001) and overall survival (p<0.001) in melanoma patients treated with immunotherapy (Opdivo, Keytruda or Tecentriq).⁴ A high TMB in this study was defined as more than 23.1 mutations/Mb. TMB was not predictive for survival for patients not treated with immunotherapy.

The third study reported the results of an analysis of predictors of metastatic urothelial carcinoma patients’ response to Tecentriq in the IMvigor 210 Phase II trial.⁵ The patients within the highest quartile of median mutational load (more than 16 mutations/Mb for platinum treated and more than 13.5 mutations/Mb for first line cisplatin-ineligible) had higher overall survival (p=0.0012 and p=0.0079, respectively) than patients in the lower quartiles. The authors also reported an improved efficacy among patients with higher PD-L1 expression. When included in a multivariable model, both PD-L1 and TMB were independent and significant predictors of response to Tecentriq (p=0.0109 and p<0.0001, respectively).

The results of these three studies suggest that a high TMB is correlated with clinical response to immunotherapy; however, each study provided a different definition of “high” TMB. While assessing TMB as a potential biomarker, the threshold to be used to identify those patients who would benefit most from immunotherapy treatment will need to be determined via consensus.

Mismatch Repair Deficiency

Two abstracts reported updated results that included more patients from the same study⁶ that focused on mismatch repair (MMR) deficiency or microsatellite instability (MSI) as markers of immunotherapy response.^{7, 8}

In the first analysis,⁷ 30 patients with MMR-deficient metastatic or locally advanced non-colorectal cancers who had received at least one prior therapy were treated with Keytruda. After a 10-month median follow-up, 53% of the patients had an objective response, and responses were observed in all of the cancer types evaluated with durable disease control. Unfortunately, patients with MMR-proficient cancers were not included in this analysis, thus this study is unable to determine the utility of testing for MMR as a biomarker for Keytruda. The second analysis⁸ focused on metastatic colorectal cancer patients treated with Keytruda and included both MMR-deficient (n=28) and MMR-proficient (n=25) patients. In contrast to the previous results for PD-L1 and TMB, there were no responses to Keytruda in MMR-proficient colorectal tumors, highlighting the selective nature for this biomarker.

Future studies will be necessary to confirm the utility of MMR deficiency as a biomarker as well as the relationship for MMR deficiency with PD-L1 expression and/or TMB. Several Phase III and Phase II trials are currently recruiting in patients with MSI-high or MMR-deficient advanced or metastatic colorectal cancer.

Conclusions

Among the FDA-approved indications for the three approved PD-1/-L1 inhibitors, only Keytruda has a label currently limiting use to a biomarker-defined patient subtype (Keytruda in PD-L1-positive NSCLC). Nevertheless, as the development of these agents is rapidly expanding across tumor types, there remains strong interest to identify predictive biomarkers of response.

Of the three possible biomarkers discussed above, MMR deficiency has the strongest evidence supporting its predictive behavior to PD-1 inhibitors. PD-L1 status and TMB may ultimately be most effective as predictive biomarkers when combined with each other and potentially other tumor-specific factors. Thus, the current oncology model of using a single biomarker to select patients for treatment may not be the best approach in the era of immunotherapy.

References

1. Bass P, et al. J Clin Oncol. 2016; 34(suppl); abstr 9015.
2. Gadgeel SM, et al. J Clin Oncol. 2016; 34(suppl); abstr 9016.
3. Spigel DR, et al. J Clin Oncol. 2016; 34(suppl); abstr 9017.
4. Johnson DB, et al. J Clin Oncol. 2016; 34(suppl); abstr 105.
5. Rosenberg JE, et al. J Clin Oncol. 2016; 34(suppl); abstr 104.
6. Le DT, et al. N Engl J Med. 2015; 372(26):2509-20.
7. Diaz LA, et al. J Clin Oncol. 2016; 34(suppl); abstr 3003.
8. Le DT, et al. J Clin Oncol. 2016; 34(suppl); abstr 103.

Introduction

In an effort to provide you with timely market feedback from the 2016 ASCO Annual Meeting, OBR and MDoutlook are pleased to share results from MDoutlook’s OncoPolls™ conducted immediately after the meeting. This report explores presentations concerning the treatment of ALK+ non-small cell lung cancer (NSCLC) and the use of checkpoint inhibitors as therapy for small cell lung cancer (SCLC).

OncoPoll™ Methodology

• Primary research phase involved a global survey to verified and validated medical oncologists and multi-disciplinary physicians with an identified clinical interest in lung cancers utilizing targeting parameters within the proprietary MDoutlook^® global cancer treater panel
• Timing: June 2016. Launched 2 days after close of 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago, IL, June 3-7, 2016
• Fielding to proprietary panel of cancer treaters, targeted by clinical interest
• Data capture via interactive web-based survey instrument, utilizing proven MDoutlook methodology and proprietary technology
• Links to discussed abstracts on the ASCO website were provided within the survey
• Reponses at data collection: 146
• Responses are from 14 countries: Austria, Belgium, Brazil, Canada, France, Germany, Italy, Japan, Poland, Spain, Switzerland, Turkey, United Kingdom and US

Key Conclusions

• On a 0 – 5 scale of 0 = no awareness to 5 = very aware, clinicians have an above average awareness
  • Higher level of awareness was seen by those outside of the US (~3.8 vs. 3.3)
  • Much higher level of awareness (nearly a full point) was seen among the attendees compared to those who did not attend (not shown)
• Clinical impact, also rated on a 0 – 5 scale of 0 = no impact at all to 5 = very important, oncologists see this new information as very clinically meaningful, with average rating of ~3.7
  • Only small differences in importance was seen between US and Ex-US and between attendees and non-attendees (not shown)
  • There is some concern that these results were from a single country (Japan) and thus may not be entirely reproducible to all patients (not shown). Large scale integration of these results into clinical practice may wait until the results of the global ALEX trial are available.

Key Conclusions

• On the same 0 – 5 scale, there is an above average level awareness about this brigatinib presentation in the US, while awareness outside of the US is well above average
  • Much higher level of awareness among the attendees (3.7) compared to those who did not attend (2.2)
• The 2^nd generation ALK inhibitor brigatinib is seen as welcome addition to the oncologists’ armamentarium for ALK+ NSCLC, as seen by the clinically important ratings
  • The clinical importance averaged ~3.5, regardless of region
  • With the higher level of awareness, more importance was seen by the attendees than with the non-attendees (not shown)

Key Conclusions

• Treaters of SCLC are aware about this new clinical data combining nivolumab (anti-PD-1) with ipilimumab (anti-CTLA-4) with level of awareness of ~3.7
  • Very high level of awareness among the attendees (4.1) compared to those who did not attend (3.0); highest level of awareness among these lung cancer abstracts by non-attendees (not shown)
• The use of the dual checkpoint inhibition in SCLC is seen as clinically important
  • US oncologists assign slightly more importance to this information, average rating of 4.0 vs. 3.6 for ex-US respondents
    • Over 1/4 of respondents rated the importance as a “5” (not shown)
  • Even with the higher level of awareness by the attendees, both attendees and non-attendees have similar views as to its importance, upon learning about this new data (not shown)

Conclusions: Immediate Impact of 2016 ASCO Presentations on Clinical Practice for ALK+ NSCLC and SCLC

• All of these studies highlight the importance of the ASCO Annual Meeting to the entire global oncology community – awareness of these presentations are high and can occur quite quickly even for those who did not attend
• The importance of these presentations suggest that integration of these results into clinical practice will happen in relatively short order, especially since most of these agents are already widely available and in use

For a more detailed analysis report, please click here to download the full report.

Submitted by Robert Stephan, VP, Research and Physician Society, and Jan Heybroek, President MDoutlook.