Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts from the ‘Lung Cancer’ category

Yesterday saw the FDA approval of atezolizumab (Tecentriq) for the second-line treatment of metastatic non-small cell lung cancer (NSCLC) (link to company press release).  According to Genentech:

“This approval is based on results from the randomized Phase III OAK and Phase II POPLAR studies. The largest study, OAK, showed that TECENTRIQ helped people in the overall study population live a median of 13.8 months, 4.2 months longer than those treated with docetaxel chemotherapy (median overall survival [OS]: 13.8 vs. 9.6 months; HR = 0.74, 95% CI: 0.63, 0.87). The study enrolled people regardless of their PD-L1 status and included both squamous and non-squamous disease types.”

The FDA approval is largely a broad one in 2L and 3L across PD-L1 expression and histologies [Link]:

“TECENTRIQ is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving TECENTRIQ.”

The approval was widely expected in light of the Phase III OAK trial data presented in the Presidential Symposium at ESMO16 meeting in Copenhagen.

Sign adjacent to #ESMO16 in Copenhagen

Sign adjacent to #ESMO16 in Copenhagen

Imagine hearing live about positive first-line data with pembrolizumab, with and without chemotherapy, negative data from nivolumab in the same setting, the 2L data for atezolizumab and two discussants drilling into both the data and broader impact of these studies to a jam packed audience that even included thought leaders from other tumour types who were also eager to hear the news. To say the atmosphere was electric would be a rather British understatement here.

We previously covered our initial impressions from that session [Link], but we also had the pleasure and privilege of interviewing a leading US thought leader in the lung cancer space after the session to garner his impressions of the data and also some perspectives on the key issues that the field is facing.

The pembro plus chemo data is already providing some controversy amongst various protagonists given there are a number of similar combination trials expected to read out over the next year to 18 months, plus much anticipation from analysts regarding the ditching of chemo for IO combos such as anti-PD–1 plus anti-CTLA–4 (BMS and AstraZeneca have keen stakes here), but what do thought leaders really think of that concept? Is that the slam dunk that many analysts seem to think it is?

This, my friends, is where things start to get a lot more complicated, akin to 3D chess in Star Trek.

What is happening now in advanced NSCLC is not how the market will look in a year or two. In many ways, the rate of approvals are outstripping the pace of science right now, but once the low hanging fruit is gone, competition will need to evolve in much more sophisticated and elegant levels.

With these questions in mind, we have a double header for you today – you can read on to find out more details from our latest though leader interview, supported by some insightful perspectives from a medical oncologist who treats lung cancer patients in private practice. Today’s post therefore covers some wide ranging discussions across the key issues in advanced NSCLC and it’s future direction.

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Please note that subscription prices will increase on Monday 24th, so if you’ve been on the fence about our upcoming coverage of #SITC2016, #ENA2016 (EORTC/NCI/AACR Mol Targets), #ASH16, #SABCS16 and #JPM17 then now is a good time to lock in at the current rates!

Copenhagen – Day 3, Sunday at #ESMO16 was a day to remember on many levels. From being carried forward by a rush of people as a massive crowd was finally let into the Presidential Symposium…

Large crowd of delegates wait patiently to enter ESMO16 Presidential Symposium

Large crowd of delegates wait patiently to enter ESMO16 Presidential Symposium

…to hearing an outstanding discussion of data by one of Europe’s leading lung cancer experts, Professor Jean-Charles Soria (@jsoriamd). He was insightful, engaging, as well as funny in places and was a hard act to follow…

Prof. Soria discussing KEYNOTE-024 data at ESMO 2016

Prof. Soria discussing KEYNOTE-024 data at ESMO 2016

The end result was a day to remember, most significantly it was one where we heard data that will change the standard of care in front-line non-small cell lung cancer (NSCLC), with the expected approval of pembrolizumab (Keytruda) for patients whose tumors have a high expression of PD-L1 (50% or more).

We’re continuing our daily digest of highlights from sessions we attended at the 2016 European Society for Medical Oncology (ESMO) Congress here in Denmark.


The sun has not shone much here in Denmark during the Congress, the above photo of Nyhavn was taken just before the meeting started, but the data at ESMO16 has shone brightly with two more publications online in The New England Journal of Medicine to coincide with their presentation in Sunday’s Presidential Symposium:

Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer (NEJM link)

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck (NEJM link).

This mini-series of daily digests over the 4 days of the Congress is intended to give subscribers a finger on the pulse on some of the buzz and conversation…. and occasionally an alternative perspective. We’ll be writing more detailed posts as part of a post-conference series.

In this post, @MaverickNY offers her topline impressions of the lung cancer data presented in the Presidential Symposium, how this will change how some patients are treated, and the resulting impact on the lung cancer landscape. Cancer Immunotherapy continues to drive changes in clinical practice, and is doing so at a very remarkable pace.

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Lung cancer, along with metastatic melanoma, has been very much to the forefront of attention in cancer immunotherapies with both nivolumab (Opdivo) and pembrolizumab (Keytruda) garnering approval as monotherapy from the FDA in second line treatment of NSCLC. A third molecule, atezolizumab (Tecentriq) has also been submitted to the authorities for this indication and a decision is expected soon.

Morgan Grafitti Wall

Street art in the Chicago West Loop

While no one is in any doubt that the response rates with monotherapy are low (in the 20% range) and the majority of people do not respond, the important thing so far is that when they do, they appear to be very durable responses. People are living longer, much longer than the 2–3 months of incremental improvement we are used to seeing with chemotherapy or targeted therapies.

The race is now on to see how we can improve things for the 80% of people with lung cancer who don’t respond to single agent therapy:

  • What can we do to help them?
  • Which combinations look more encouraging?
  • Should we treat beyond progression?

To answer these questions, we interviewed Dr Stephen Liu and discussed his views on some of the cancer immunotherapy combination studies presented at ASCO last week.

Dr Stephen Liu

Dr Stephen Liu at ASCO 2016

Dr Liu is a lung cancer expert at the Lombardi Cancer Centre at Georgetown University, and is actively involved in numerous clinical trials, particularly in Developmental Therapeutics.

Georgetown’s founding principle is Cura Personalis, which translates as care of the whole person. It “suggests individualized attention to the needs of others, distinct respect for unique circumstances and concerns, and an appropriate appreciation for singular gifts and insights.”

Dr Liu embodies this ideal, advocating for his patients for access to the best research advances, including genomics and clinical trials of promising agents.  At ASCO, he kindly highlighted some of the important findings from Chicago and offered context on why they matter to the field.

He told us one combination was “potentially transformative” and could be “practice changing” in lung cancer with more data.

Intrigued? To find out what these important trials are and which ones to watch out for, subscribers can log-in to read the article or you can sign-up by clicking on the Blue Box below.

It’s Friday 13th, a day often feared by the superstitious, but for AstraZeneca it certainly portended good news with the FDA approval of AZD9291 or osimertinib (now Tagrisso) in EGFR T790M mutation-positive lung cancer – three months ahead of the PDUFA date. Jonathan Rockoff, a reporter at the WSJ, was the first to announce it in my Twitter stream:

Tagrisso 80mg

Tagrisso 80 mg. Picture credit: AstraZeneca

The FDA announcement for Tagrisso (generic name is osimertinib) can also be found here and the actual label here.

Note that it is now available under accelerated approval, based on tumor response rate and duration of response. This means that phase III confirmatory trials, including survival data will be needed for full approval.

As part of our ongoing series on the T790M niche, this is also a timely opportunity to catch up with the latest data that was presented earlier this month at the AACR-NCI-EORTC Cancer Therapeutics and Molecular Targets meeting in Boston.

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With the recent approvals of nivolumab (Opdivo) and pembrolizumab (Keytruda) in advanced lung cancer as well as new checkpoint inhibitor data presented on atezolizumab at the European Cancer Conference in Vienna, there are several new lung cancer immunotherapy controversies to consider such as…

  • How do we choose between docetaxel chemotherapy versus anti-PD1/PD-L1 immunotherapy?
  • Which checkpoint should we choose?
  • Is the PD-L1 biomarker useful and important?
  • Do the company assays differ?
Dr Jack West

Dr Jack West

Dr Jack West (Seattle) got the ball rolling on some of these issues earlier this month, generating quite a spirited and useful debate on Twitter, demonstrating that clinical decisions in this area are not as cut and dried as many might think.

In addition, we spoke to a number of lung cancer experts in Vienna for their perspectives on the data, the biomarkers, treatment paradigms and other critical issues.

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On Friday last week, AstraZeneca confirmed that their combination trial for osimertinib, as it’s expected to be called or AZD9291, as it’s more commonly known (anti-EGFR mutant, T790M inhibitor) plus durvalumab (MEDI–4736, anti-PD-L1) in non-small cell lung cancer (NSCLC) is on clinical hold following an increase in ‘interstitial lung disease-like reports.’

As companies with checkpoint inhibitors and other immunotherapy agents expand beyond monotherapy into logical combinations, is the risk of increased ILD from combining an EGFR inhibitor with a checkpoint something other companies need to watch out for?

By the way, we strongly disagree with the reported conclusion of Goldman Sachs on this issue – and here’s why…

Today’s article explores this controversial issue in more depth.

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Over the last decade we have seen some real progress with some subsets of lung cancer, particularly in EGFR mutated and ALK translocated tumours.  Indeed, an incredible amount of translational work has emanated from just a few groups based in Boston, New York and Hong Kong.

Dr Jeff Engelman Source: MGH

Dr Jeff Engelman Source: MGH

At AACR earlier this year, Dr Jeffrey Engelman (MGH, Boston) gave a fantastic talk not just about heterogeneity, resistance mechanisms, but also on how lung cancer can transform. Included in his review was the role of biospies and how he sees those evolving.

I’ve been meaning to write up this important talk since April, but decided to wait until the key publications that were in press at the time were actually published – it was a longer wait than expected!

In general, it is our policy to write up published, rather than unpublished data, out of respect to researchers.  It also makes it more useful to readers when the translational and clinical data is publicly available for those interested in reading the in-depth research articles.  We also gathered commentary from other though leaders in the lung cancer space for some additional insights.

To learn more about the latest developments in the underlying complexity and clinical implications for EGFR+, T790M-positive and ALK-positive lung cancers, subscribers can log in below or you can sign up to read our comprehensive review of this topic.

AAI LogoNew Orleans – At the 2015 annual meeting of the American Association of Immunologists (AAI) leading experts came together to share their insights on the Promise of Cancer Immunotherapy.”

The audience at #AAI2015, in an artic chilled hall, heard from an outstanding panel of speakers, many of whom flew in specially:

  • Immunologic Checkpoint Blockade: Combinations and Mechanisms, Jedd Wolchok (MSKCC)
  • Immune Checkpoint Therapy: Clinical Success and Next Steps, Padmanee Sharma (MD Anderson)
  • Improving Cancer Treatment Through Immunotherapy Combinations: Combination MAb Therapy: Dual tumor & Immune Targeting, Holbrook Kohrt (Stanford Cancer Institute)
  • Curative Potential of T-Cell Transfer Immunotherapy for Cancer, Steven Rosenberg (Surgery Branch, NCI)
  • PD-1 pathway blockade in cancer therapy: new frontiers, Suzanne Topalian (Johns Hopkins)
Dr Steven Rosenberg (NCI)

Dr Steven Rosenberg (NCI)

Cancer Immunotherapy is such a fast-evolving field that at Immunology 2015, we heard data that wasn’t at the annual meeting of the American Association for Cancer Research (AACR), just a few weeks ago.

Several presenters also put in context data that will published at the forthcoming ASCO annual meeting.

If you’d like to hear more about some of the checkpoint inhibitor data at AACR15, do listen to the first episode of the Novel Targets podcast (if you haven’t already done so).

It’s available as a free download on SoundCloud and on iTunes.

This post offers a top-line summary of some of the key messages we heard in the #AAI2015 symposium.

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With the sheer breadth and depth of immuno-oncology data being presented at even the American Association for Cancer Research (AACR), several readers were prompted to write in and ask:

“Is this the end of the road for TKI therapies? Should we even bother to continue working on these agents?”

Good question.

There was actually quite a bit of interesting data on regular novel targeted therapy to discuss, although I do concede that much of the mass media news focusing on the immuno-oncology tsunami in Philadelphia effectively drowned out targeted therapies and the results coming out in that space.

Reading Market Philly Chocolate TowerTo maintain the balance between novel targeted agents and immunotherapy, here’s a review of some of the interesting new developments that I came across at AACR, from both the poster halls, as well as some of the thought leaders in this space.

When you stack up the emerging evidence in several tumour subsets, there are quite a few tasty morsels that are worthy of further discussion!

I’d like to take this opportunity to extend a warm welcome to all the new subscribers who took advantage of the AACR Special Offer to continue their education and learning about the exciting new developments in cancer research.  Thank you for joining our conference coverage service, we really appreciate it.

To learn more about the hot topics in targeted therapies for cancer research, you can log in or sign up in the box below.  Read on…

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