AACR 2018 lung cancer advancements: how will the findings translate in clinic?


At the AACR Annual Meeting 2018 (April 14–18, IL, USA),back-to-back presentations highlighted the advances in immunotherapy treatments for lung cancer, the deadliest cancer worldwide with approximately 1.7 million deaths per year [1]. Researchers from across the globe presented their published anti-PD-1/anti-PD-L1 trials and the results will change the way some lung cancers are approached.

The treatments:

  • Pembrolizumab (Keytruda ®) plus chemotherapy fared significantly better than chemotherapy alone in nonsquamous Non-Small Cell Lung Cancer (NSCLC) in the Keynote-189 trial, as published in The New England Journal of Medicine 
  • Nivolumab (Opdivo ®) plus ipilimumab (Yervoy ®) had significantly higher progression-free survival than NSCLC patients treated with chemotherapy when they had a high Tumor Mutational Burden (TMB > 10 mutations/Mb) in the CheckMate-227 trial, also published in The New England Journal of Medicine
  • Atezolizumab (Tecentriq®) plus bevacizumab (Avastin®) and chemotherapy showed an improvement in progression-free survival over bevacizumab and chemotherapy in the IMpower150 trial of nonsquamous NSCLC patients

Each of these trials represents an achievement in progress for NSCLC patients; all three will become first-line treatments for a metastatic disease with a 5 year survival rate of 10% or lower [2]. Without question, each of these alone represent substantial progress in the fight against lung cancer.  Taken together, they are a triple dose of good news and hope for those diagnosed with this disease. However, there’s an asterisk to all the hoopla and hype.

The issue: all three of these trials were structured in ways that make apples-to-apples comparisons difficult and scientifically unsound. Comparing hazard ratios and eyeballing control arms do not give scientists the comfort of a level playing field when considering the results of each treatment/combination in relation to each other. Ask most researchers to tell you which result set is better and you are liable to receive a litany of disclaimers about what the data shows and how the results shouldn’t be interpreted as comparable.

The conundrum: physicians in the clinic and patients who see them ARE going to compare A vs. B vs. C when discussing their lung cancer treatment options. There is simply no way around this – it’s arguable that any NSCLC patient NEEDS to have each option presented (upon regulatory approval), and make a decision that is right for them based off the known information.  They will have more options, but the knowledge of how (and when) to apply those options isn’t as advanced.

Understandably, part of this quandary is the desire to get a treatment approved quickly, by any means necessary – often a comparison arm that is likely to be inferior.  Many a trial can be described as “aiming for faster time-to-market” for a drug, which often means life-altering/extending/saving treatments get to more patients who need them. Cynics may point out this means quicker marketability and profitability – pharmaceutical companies lose money, and potentially market share, the longer a drug sits on the shelf waiting for the regulatory blessing. So it is clearly in everyone’s best interest to get treatments to the general public in an expeditious manner.

Sometimes the easier road to regulatory approval leaves the individuals giving the treatment, and those receiving it, with more questions than answers. It is great there are more tools in the toolbox for lung cancer patients. Not knowing exactly when to use each tool, though, means physicians are left to offer patients treatment options without having the backing data that supports Choice A vs. Choice B vs. Choice C – only “Choice A vs. standard of care a”, “Choice B vs standard of care b”, “Choice C vs. standard of care c”… There are numerous caveats to why results are given the way they are, but the bottom line for patients often means it is difficult to compare multiple therapies clearly against one another.

There are numerous opportunities to enhance the current lack of data.  First, getting clinical trials to even report their data would be an enormous hurdle to clear – perhaps publicly trial-shaming them is the way to go. Second, demanding patient-relevant outcomes be a part of EVERY trial– with patient input into design – would be progress towards real-world application of clinical data. While we’re asking for the improbable, developing a standard set of measures for all oncology research would go a long way towards clarifying how to balance Checkpoint Inhibitor X’s overall response rate vs. Monoclonal Antibody Y’s progression-free survival. None of these are unreasonable requests, and if the industry is aiming to be as patient-centric as is being claimed, all three of these initiatives would begin to validate those centricity claims.

Clinical trial design is a slow and cumbersome beast to change direction; with the ever-increasing number of stakeholders with input, it’s a wonder most trials even make it into the clinic.  It is hard to fault any one entity for the inability to discern between treatments – the investment of time and resources into just getting a drug approved is already astronomical. However, it is certainly not impossible to generate BETTER data to be used in decision-making.

As oncologists and oncology professionals, patients look to you every day for guidance in their healthcare – guidance that you will base, in no insignificant part, on hard data that comes from clinical trials like the trio mentioned above. Many of you have likely faced a similar scenario, and hopefully, have used your education and experience to guide the treatment discussion and decision to its optimal conclusion. Wouldn’t it be beneficial to have the backing of solid comparison data available to supplement those conversations? Change will only come from within, and together, patients and their physicians will need to be the one demanding cleaner, clearer results.

References:

[1] www.who.int/en/news-room/fact-sheets/detail/cancer

[2] www.cancer.org/cancer/non-small-cell-lung-cancer/detection-diagnosis-staging/survival-rates.html

Discover T.J.’s perspective on immunotherapy advancements

Discover T.J.’s perspective on the aftermath of treatment

Biography

T.J. Sharpe is a Stage IV melanoma patient who shares his journey through cancer in the Patient #1 Blog on www.oncology-central.comwww.philly.com/patient1/www.SkinCancer.net, and on www.NovartisOncology.com. He was diagnosed in August 2012 with melanoma tumors in multiple organs, only 4 weeks after his second child was born. Since then, he has undergone six surgeries and four immunotherapy treatments over two different clinical trials. The initial failures, and subsequent complete response, have been chronicled in his blog posts since December 2012. In addition to writing, he is a keynote speaker and consultant to the biopharma and clinical research industries, bringing an educated patient voice as a true stakeholder in challenging healthcare’s status and making a difference in patients’ lives via his company, Starfish Harbor LLC. A South Jersey native, T.J. lives in Fort Lauderdale, FL, with his wife Jennifer and two young children, Josie and Tommy.