GRACE :: Lung Cancer

Mesothelioma

Denise Brock

ASCO 2017 – Lung Cancer – Emerging Options for Malignant Pleural Mesothelioma

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H. Jack West, MD
Medical Director
Thoracic Oncology Program Swedish Cancer Institute
President & CEO, GRACE
Matthew Gubens, MD
Thoracic Oncologist
Thoracic Surgery and Oncology Clinic
UCSF Helen Diller Family Comprehensive Cancer Center
Jyoti D. Patel, MD
Director Thoracic Oncology
University of Chicago Medicine

 

Drs. H. Jack West, Medical Director of the Thoracic Oncology Program at Swedish Cancer Institute in Seattle, Washington and President and CEO of GRACE, Matthew Gubens, Thoracic Oncologist at the Thoracic Surgery and Oncology Clinic of the UCSF Helen Diller Family Comprehensive Center in San Francisco, California, and Jyoti Patel, Director of Thoracic Oncology at University of Chicago Medicine gathered post meeting to discuss new information from ASCO 2017 regarding lung cancer.   In this roundtable video, the doctors discuss Emerging Options for Malignant Pleural Mesothelioma.



 

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GRACE Video

Promising Early Results with Immunotherapy for Mesothelioma

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WCLC_2015_03_Mesothelioma_Immunotherapy_Promising_Early_Results

 

Drs. Leora Horn, Ben Solomon, & Jack West review early promising data on the potential activity of immune checkpoint inhibitors in the treatment of malignant pleural mesothelioma.

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Transcript

Dr. West:  Turning to the issues of what’s emerging in mesothelioma, it seems that there’s a lot of interest in immunotherapies in this setting. Any sense of early data in that, how hopeful you are?

Dr. Solomon:  So, it was with pembrolizumab, and again, a small study, and a response rate of about 29%, and I think that’s encouraging, and I think this is in patients who had prior platinum pemetrexed, and this is a setting where there isn’t a standard second-line treatment, so I think that sort of response rate, again, is a meaningful response rate, and there are a number of other studies that are going with the other different PD-1 or PD-L1 inhibitors, alone or in combination with CTLA-4 inhibitors.

Dr. Horn:  The pembrolizumab study, from what I remember, was only in PD-L1-positive patients.

Dr. Solomon:  I think that’s right, and we may talk about PD-L1 as a biomarker later, but I think an interesting observation was that the didn’t find that the degree of PD-L1 scoring correlated with the likelihood of response, in mesothelioma.


GRACE Video

Is the Survival Benefit with Avastin Added to Chemotherapy Enough to Change the Standard of Care in Mesothelioma?

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WCLC_2015_Avastin_Chemotherapy_Mesothelioma_Survival_Benefit_Enough

 

Drs. Ben Solomon, Leora Horn, & Jack West discuss highlights of a French randomized trial that demonstrated a significant survival benefit from addition of Avastin (bevacizumab) to cisplatin/Alimta in patients with malignant pleural mesothelioma.

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Dr. West:  So, one of the other topics that’s covered in this broad thoracic malignancies conference is mesothelioma, where one of the biggest bits of news that we got this year actually came at ASCO, earlier this year, in a French trial that showed that adding Avastin (bevacizumab) to standard chemotherapy, in this case, cisplatin and Alimta (pemetrexed), seemed to improve survival in a clinically significant way. What do you think of these data — is this changing practice for you or around you, Ben?

Dr. Solomon:  Sure, look, I think it’s an important study — the initial study that showed benefit of cisplatin and pemetrexed, over cisplatin alone, was the first phase three study that showed a survival benefit in mesothelioma. This is the second study, and I think the benefits are meaningful. There was an improvement in progression-free survival of about two months — the improvement in overall survival was a bit more than that. So, I do think that that difference is meaningful, and I think it’s likely that bevacizumab, in that context, will get incorporated into standard practice.

Dr. West:  What do you say?

Dr. Horn:  I think that is possible — what I worry is that pemetrexed and bevacizumab together is a more toxic combination, and it is not as easy and as tolerable as pemetrexed alone, but for those patients who can tolerate it, it is a good, new treatment option for them.

Dr. West:  So it’s not something you’re uniformly inclined to incorporate for most or all of your patients with mesothelioma?

Dr. Horn:  It’s such a rare disease, so not right now. What I also worry about is a lot of the mesothelioma patients are older, and, so, that same worry about tolerability.


GRACE Video

Improved Survival in Malignant Pleural Mesothelioma with Avastin Added to Chemotherapy

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ASCO 2015 Highlights 11

 

A French study presented at ASCO 2015 showed a survival benefit with Avastin (bevacizumab) added to standard chemo, unlike a prior US study. The doctors discuss the influence of this trial and future potential benefits from immunotherapy in mesothelioma.

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Lung Cancer Leaps Expected at Scientific Meeting

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Dr. Thomas John is a thoracic oncologist at the Olivia Newton-John Cancer and Wellness Centre in Australia.

The American Society of Clinical Oncology’s (ASCO) Annual Meeting brings together 30,000 oncology professionals from around the world. Educational sessions feature world-renowned faculty discussing state-of-the-art treatment modalities, new therapies, and ongoing controversies in the field. The meeting will take place May 29 – June  2, 2015. 

ASCO 2015 promises to advance our knowledge of lung cancer. There are some positive studies that will impact treatments. In particular, it has been a big year for treatment advances for non-small cell lung cancer (NSCLC) which will provide insight into future diagnostic and therapeutic directions.

Immunotherapy

In lung cancer, as expected, several immunotherapy trials will be reported. The Checkmate 017 study, which investigated Opdivo (nivolumab) compared to Taxotere (docetaxel) in patients with squamous cell lung cancer in the second line setting, has already been reported as a press release. Nivolumab was associated with a three month improvement in overall survival compared to chemotherapy, with less toxicity. PD-L1 expression was not prognostic or predictive. These data are from a Phase III study and clearly indicate that immunotherapy is superior to Taxotere from both an efficacy and toxicity perspective.

Similarly the POPLAR study, which investigated Roche’s PD-L1 inhibitor MPDL3280A, was designed to investigate superiority against Taxotere. This study included both adeno- and squamous cell carcinomas, and the interim analysis showed a survival and response benefit restricted to tumours with high PD-L1 expression. For MPDL3280A, the rates of PD-L1 positivity appear to be lower than other assays. The assay measures PD-L1 expression in “tumour infiltrating lymphocytes” (immune cells invading the tumour) rather than tumour cells directly. The correlation between PD-L1 expression and response from this study appears striking, with no response in PD-L1 negative tumours.

There are many other abstracts pertaining to the immune checkpoint inhibitors being presented at ASCO this year. The Checkmate 017 study is practice-changing and suggests that Opdivo should be given to all squamous cell patients, regardless of PD-L1 status. Combinations of CTLA4 blockade (another means of activating the immune system by removing the brakes)/PD-L1 and pathological assessment of PD-L1 in molecularly subtyped tumours will also be reported.

It appears that PD-L1 expression certainly enriches for a group likely to derive maximum benefit, however depending on the assay, up to 20% of PD-L1 negative patients also respond, and indeed compared to chemotherapy these negative patients who respond also derive clinically meaningful survival benefits. There are further issues with tumour heterogeneity (differences in molecular characteristics of cancer cells even within the same tumour), and sampling making the companion biomarker a topic we will be talking about for many years to come.

Immune checkpoint inhibitors will be one of the most talked about treatments at this ASCO, as there are emerging data in small cell lung cancer, mesothelioma and in various permutations and combinations in molecularly driven NSCLC.

Targeted Therapies in Lung Cancer

Recently, AZD9291 was reported to result in significant response and survival benefit in patients with an acquired resistance mutation (T790M) that had developed after using an EGFR TKI for their EGFR mutant NSCLC. In a subset of patients from the Phase I study, a first line cohort was recruited. AZD9291 appears to be a highly effective drug in the first line setting, with an objective response rate of 70%, a disease control rate of 97% and a toxicity profile that is a lot better than Iressa (gefitinib) or Tarceva (erlotinib). The main question, however, is whether AZD9291 prolong progression free survival. These data are not mature enough, and median progression free survival has not been reached to date. Subsequent studies have already begun recruiting patients that compare AZD9291 to both chemotherapy and an oral TKI.

Other interesting studies show that the combination of BRAF and MEK inhibition (Tafinlar (dabrafenib)) plus Mekinist (trametinib) in BRAF mutant NSCLC is more effective than Tafinlar alone. It will be interesting to see how many patients were screened to discover this subset of patients. It is notable to see similar response data to that seen in melanoma. We still need to determine whether using immune checkpoint inhibitors in this subset is also as effective as it is in melanoma.

Gilotrif compared to Tarceva in squamous cell cancers (Lux Lung 8) will be reported as showing a survival benefit. However, the clinical utility of the one month improvement is likely to be questioned especially given the toxicity of this agent, the widely recognized minimal to modest efficacy of Tarceva in this setting, and the other agents becoming available.

Brain Mets

Finally, the plenary session will include a study where patients with 1-3 brain metastases were randomised to either receive stereotactic body radiation therapy (SBRT) plus whole brain radiation therapy (WBRT) or SBRT alone. Over 60% of patients in this study had lung cancer. The addition of WBRT controlled the disease but was associated with significantly greater cognitive decline and no survival advantage. This study suggests that WBRT should not be added to SBRT. By extrapolation, should we be using WBRT at all for 1-3 brain mets? We do not know the details here, so the question of surgery also comes to mind, but that would be contingent on having disease control extracranially.

Mesothelioma

For mesothelioma, data from the Keynote 028 study, which investigated Keytruda (pembrolizumab) after failure of initial chemotherapy has already been reported at the AACR Annual Meeting in April. It showed that for around one quarter of patients, the disease actually shrank, and the disease remained stable in about 50%. These data are encouraging and are launching several larger Phase II/III studies.

ASCO will showcase several abstracts pertaining to mesothelioma, including one that it is practice changing. The MAPS trial was initially a Phase II French study whose interim analysis was recently reported, and a decision to continue the trial was made. Here the Phase III part of this study is reported. Patients were randomised to receive standard cisplatin/pemetrexed chemotherapy +/- Avastin (bevacizumab/bev) 15mg/kg. This was a large trial with 448 patients. The addition of Avastin prolonged progression-free and overall survival by two months with minimal increase in toxicity. This is the first time an addition to overall survival has been reported in a Phase III trial in mesothelioma since the paper that established the value of cisplatin and Alimta for mesothelioma, 12 years ago!

In mesothelioma, it is good to see some positive results with Avastin, although there will likely be some debate about whether the cost is justified for a survival advantage of only 2 months.

Follow all of the ASCO happenings on Twitter at #ASCO15, @cancerGRACE, and @jackwestmd.


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