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Modest improvements in lung cancer carry steep costs, but potential solutions exist
The 16th World Conference on Lung Cancer — sponsored by the International Association for the Study of Lung Cancer — took place in September in Denver, culminating the term of Fred Hirsch, MD, PhD, as association president.
As in so many other fields of oncology, the molecular revolution attained increasing dominance in the scientific agenda, although the value proposition also has begun to take on increased importance.
Impact of overregulation
Many sets of interesting data appear to be laying the foundations for true progress in the field of lung cancer, some of which are covered in this issue of HemOnc Today. Increasing refinement of histological sub-classification of lung cancers are predicated on new details of molecular expression and genetic mutation.
However, before addressing molecular prognostication, I think it is worth signaling the presentation of David J. Stewart, MD, FRCPC. He made several important points:
As we consider the modest improvements in outcomes of lung cancer treatment and the burgeoning associated costs, as a medical community we would do well to think carefully about the implications of this presentation, particularly in view of the politics of an impending presidential election.
It appears that — following the example of the previous American Joint Committee on Cancer classification system for germ cell tumors — the new WHO classification of lung cancers will now incorporate the implications of molecular testing, as reported by William Travis, MD.
In addition, minor tweaking of the system — including the ordering of tumors by prevalence rates — and minor tinkering with TNM staging will be incorporated. These probably will not influence treatment greatly, but they will make historical comparisons of different series even less valuable.
Therapeutic advances
From the therapeutic standpoint, several sets of potentially important data were presented.
Among the most prominent were the studies linking the expression of PD-L1 and responsiveness of lung cancer — in particular, squamous malignancy — to the range of immunoactive agents, such as nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb), with the attainment of PFS figures at 6 months that were emergently respectable.
I continue to be bothered by the focus on PFS, with the endpoint of OS being viewed as “exploratory,” as this seems a good way to avoid complete and critical assessment of the utility of novel compounds.
In the context of molecular analysis, it will be extremely important for our very clever colleagues who dabble in molecular biology to review the basic principles of statistical analysis. It is extraordinary to see the number of times that potentially important studies were somewhat dismissed, based on insufficiently impressive P values when the size of the case series — with heavily selected and reduced patient numbers — could not possibly have achieved statistical significance.
On a completely separate note, a study conducted by Barbara J. Gitlitz, MD, and colleagues on young patients with lung cancer seems important for three reasons: the focus on a puzzling and challenging clinical problem with very high stakes; the recruitment of patient participation through a website focused on lung cancer in young people, a harbinger of community outreach of the future; and the demonstration of actionable mutations.
Gitlitz noted that the majority of study participants presented with advanced disease and had adenocarcinomas. Also, a surprisingly high proportion had driver mutations of ALK (44%) and EGFR (26%), which were actionable and could easily change the approach to management of these young patients.
In memoriam
Before winding up this missive, I would be negligent if I didn’t mark the recent passing of one of the true icons of oncology, Gianni Bonadonna, MD (1934-2015).
Bonadonna — one of the most prominent Italian oncologists — had a vast impact on the international practice of oncology, having been credited with being one of the founding fathers of the strategy of adjuvant systemic treatment of breast cancer, as well as having been one of the developers of the standard ABVD regimen for Hodgkin’s disease.
He was a thoughtful and engaging speaker, writer and innovator, and a Renaissance man in the truest sense of the phrase. In addition to his work in oncology, and having founded the Fondazione Michelangelo in Italy, he wrote an authoritative work on the Sepoy Rebellion in India. His impact on oncology will continue to be honored by ASCO through its Gianni Bonadonna Breast Cancer Award and Lecture, and the Gianni Bonadonna Hodgkin’s Disease Award and Lecture, instituted by the International Symposium on Hodgkin’s Lymphoma in Cologne, Germany.
His presence on the international scene will be greatly missed.
References:
The following were presented at World Conference on Lung Cancer; Sept. 6-9, 2015; Denver.
Gitlitz BJ, et al. The genomics of young lung cancer study.
Stewart DJ, et al. Impact of time to drug approval on potential years of life lost: The compelling need for improved trial and regulatory efficiency.
Travis WD. 2015 WHO classification of the pathology and genetics of tumors of the lung.
For more information:
Derek Raghavan, MD, PhD, FACP, FRACP, FASCO, is HemOnc Today’s Chief Medical Editor for Oncology. He also is president of Levine Cancer Institute at Carolinas HealthCare System. He can be reached at derek.raghavan@carolinashealthcare.org.
Disclosure: Raghavan reports no relevant financial disclosures.