This may be one of the most important advances in cancer treatment this year, and almost no one in the major media has reported it, as best I can tell:
Osimertinib (trade name Tagrisso™) made a huge difference in outcomes for patients with early stage EGFR-biomarker positive lung cancer when used as adjuvant (preventive) therapy after primary treatment (complete surgical resection in all patients; adjuvant chemotherapy in some).
When I say huge, I mean huge: EGFR+ patients with stage IB to IIIC non-small cell lung cancer (the most common type of lung cancer) had a close to 90% survival at two years while 52% of those in the placebo group were alive at that point. Overall, treatment with osmertinib resulted in an 80% reduced chance of dying for patients who received it as part of the clinical trial.
I have been a medical oncologist for close to 50 years, and I can confidently say that I have seen only a handful of similar reports where I thought the news had an immediate and significant, undeniable impact on the outcomes for cancer patients. This is one of those times, similar to the impact of imatinib (Gleevec™) in chronic myelogenous leukemia and GIST tumors, trastuzumab (Herceptin™) in breast cancer, immunotherapy in general and specifically in melanoma and lung cancer, and now osimertinib in lung cancer.
When lung cancers are diagnosed, tests are run to determine what genetic mutations are present and whether those changes can guide the choice of treatment, primarily in advanced disease (sadly, few patients with lung cancer have an early diagnosis). EGFR is one of those mutations, and in fact was the first one discovered where we had drugs that could improve outcomes for patients with advanced disease. Today, as science and treatment has progressed, we have a number of identified mutations and targeted therapies that have helped improve the outlook for those with advanced lung cancer at the time of diagnosis. Osimertinib is one of those drugs.
However, although we now know that osimertinib is useful in patients with advanced lung cancer who have the EGFR mutation, we did not know whether it would make a difference in patients who were diagnosed earlier in the course of their disease, where the tumors could be completely removed surgically. This report clearly and emphatically answers that question: yes, it makes a real difference, no question.
In this trial, first reported in June at the annual meeting of the American Society of Clinical Oncology and this week in the New England Journal of Medicine, investigators divided patients with early stage lung cancer that was EGFR+ into two groups: After patients had their primary treatment for lung cancer (all had surgery; some had adjuvant chemotherapy; none had radiation therapy) they were randomly assigned to receive either osimertinib or a placebo. Doctors and patients did not know which group they were assigned (even today as the clinical trial continues they do not know according to the research report).
The results are nothing short of amazing: a total of 682 patients were randomized, 339 to receive osimertinib and 343 placebo. In every way the study was analyzed, whether by stage, by disease free survival, by overall survival, or by how often the cancer came back in the central nervous system, the osimertinib group came out way better. No question, no close calls: clearly a very real and very significant improvement in every outcome. You can see for yourself in the graph copied below, one of several in the report.
I need to emphasize that while this report is exciting, there are some cautions that we need to recognize:
1) Only a small percentage of patients with non-small cell lung cancer are EGFR positive: about 10-20% of white patients, and 50% of Asian patients. So this result will only apply to a small number of the patients diagnosed with lung cancer, and only for patients diagnosed before the disease has spread outside the lung or is not removable with surgery—an even smaller number.
2) The treatment was not without side effects, which on occasion resulted in some patients stopping treatment. 10 patients who took osimertinib developed lung problems that reversed when the treatment was stopped, however there was no indication of serious effects on the heart.
3) These results are based on what is called “disease free survival”. Although we know patients who received the placebo had a median survival of 27.5 months (half lived longer, half lived less), we still don’t know the “halfway” number for the patients who received osimertinib. Having that overall survival number is important to understanding the true impact of this treatment. The ultimate question is whether the patients on osimertinib had from lung cancer delayed or in fact may have been cured by use of this medication.
4) It is important to note in this study that patients who had relatively early diagnoses and received the placebo treatment, survival wasn’t as good as we would like even with an early diagnosis. That means that even with catching the disease early and being able to surgically remove it, almost half the patients who received the placebo had died after two years if they didn’t receive the osimertinib. So while early diagnosis in lung cancer is important, it still doesn’t mean cure for many patients.
In June 2019 I wrote a blog reflecting on my thoughts about what we could accomplish in reducing the burden of lung cancer if we applied all the knowledge available about prevention, screening, diagnosing and treating the disease. 16 months later we are beginning to realize that promise: we are now seeing longer survivals in this dread disease. The results reported here will make a further contribution to that progress.
However we must recognize these new early diagnosis and treatment approaches are not enough: As I had written in that blog, we must constantly avail ourselves of every opportunity to help those at high risk of lung cancer find the disease early and get the best treatment, and recognize that there are many out there who are not considered at high risk yet develop lung cancer and also require the best treatment available. We have an obligation to make certain that opportunity is a reality.
Even with this good news, we cannot forget: Yes, we are doing better when it comes to preventing, diagnosing and treating lung cancer, however sadly we are a long way from doing our best.
–NEJM.org; Published September 19, 2020