Using Effective Cancer Therapies Earlier — Does It Always Work?

If you have an effective tool, should you always use it more often or in more situations?

It all depends on the specifics — and in the case of medical issues, it requires careful thought and well-designed clinical trials. Lung cancer was one of the earlier beneficiaries of the cancer immunotherapy revolution that is now at the 20-year mark.

For cancers that do not have a genomic target that can be addressed with an EGFR, ALK/ROS1 and other such inhibitors, immunotherapy has made significant impacts on survival in advanced lung cancer. With increased awareness, better imaging technology and the advent of low-dose screening CT scans for those at risk for lung cancer, earlier detection is becoming more common. Surgery has long been the mainstay for localized and operable lung cancer.

However, recurrences due to residual microscopic disease that cannot be seen on scans are common, and usually not curable. Preventing recurrences with “adjuvant” chemotherapy became a standard treatment to address this, and was complemented with radiation for stage 3 cases, but the reductions in risks were modest.

As immunotherapy became the standard of care for many cases of metastatic lung cancer because it was much more effective than chemotherapy alone, the natural question was whether this could be moved to the adjuvant setting. But immunotherapy is not without its consequences — side effects that are sometimes severe and may be fatal.

Where should the line be drawn so that the improvement in mortality would clearly outweigh the harms of treatment? The only way to answer this was with clinical trials — and not just one, but several with different designs and using various immunotherapies.

Through the deliberate and innovative designs of these studies, as you will read about in this issue of CURE®, recurrences have been cut by more than one-third with this approach. And there is the potential to go even further as refinements in harnessing the immune system against cancer continue with more discoveries in the lab and newer agents that home in on more recently discovered modulators of the immune system.

The stories of the patients in our feature on this topic illustrate how they have become partners in therapeutic advances by, in some cases, participating in trials, or simply taking the time to understand their disease, the powerful treatments involved, and appreciating what they could do to help their own cause by learning the protocol and knowing what side effects to report to their care team.

The field is changing more quickly than it ever has — immunotherapy being a
big part of the latest successes but aided greatly by the migration of successful therapies to earlier in the disease process.

DEBU TRIPATHY, M.D.

EDITOR-IN-CHIEF

Professor and Chair, Department of Breast
Medical Oncology, Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center Houston, TX

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