Checkpoint Inhibitors Before Surgery Could Improve The Odds For Lung Cancer Patients

The development of immune checkpoint inhibitors and the subsequent approval of Keytruda and Optdivo to treat advanced lung cancer has already given a huge boon to thousands of patients across the US every year. Now a new study, LCMC3, to be discussed in depth at this year’s meeting of the American Society of Clinical Oncology, suggests that drugs like this could give benefit to thousands more.

A phase II clinical trial conducted by the Lung Cancer Mutation Consortium, an organization coordinated by the Lung Cancer Research Foundation, found that giving artezolizumab (brand name Tecentriq) to patients with operable non small cell lung cancer (NSCLC) before surgery could also be extremely beneficial. Of the first 101 patients in the trial, 90 had surgery after being treated with artezolizumab. Of these patients, 15 had a major pathologic response to the treatment, defined as 10 percent or fewer viable cancer cells being found in the tumor tissue that was removed. Four patients had a complete response, meaning that there was a complete absence of residual cancer after the treatment, seventy two had stable disease, and four saw their disease progress.

While this is only a small trial, these are extremely promising results, and will almost certainly lead to a much larger stage III trial. “This is exciting because these results now give the impetus to go ahead with a much larger trial in the next step,” Dr Mark Kris of Memorial Sloan Kettering Cancer Center told SurvivorNet. “The biggest impact will come when those stage III results are read out. That’ll take nearly a decade, but the implication of this trial is that they’re going to be positive.”

Because the immune checkpoint therapy was given before surgery, in this trial it was possible to see just how effective the artezolizumab had been by studying the tumors that had been removed. That, says Dr Kris, has allowed the researchers to see the effects of the drug with a much greater accuracy, and a confidence that they will be replicated in a larger population.

While a lot more data needs to be gathered, the potential of using artezolizumab in the neoadjuvant, or before main treatment, setting is startling, and could one day lead to a wider use of immune checkpoint therapies for lung cancer.

“Immune checkpoint therapy is now standard of care for patients with advanced (metastatic) lung cancer, and this study suggests that it may also have benefit in early stage, operable lung cancer” said the study’s lead author, David Kwiatkowski, MD, PhD, senior physician at Dana-Farber/Brigham and Women’s Cancer Center.

Surgery remains the only potentially curative treatment for early stage NSCLC patients, and is effective in nearly half of cases. However, there are also many patients who won’t achieve a cure following surgery, and around 30 percent to 55 percent of patients with NSCLC will develop a recurrence. It’s that proportion of patients, whose cancer comes back after surgery, that the LCMC3 trial is targeting. Whilst stressing that it’s still early days, Dr Kris thinks that the results of this trial indicate that the approximately 50 percent of lung cancer patients currently cured by surgery could rise to up to 70 percent with the addition of targeted therapies and immune checkpoint inhibitors like artezolizumab given before main treatment.

While this is encouraging, there is still a long way to go before anything can be said for certain, but it does look like immune checkpoint inhibitors could well give even more benefit to lung cancer patients if given upfront. It’s a strategy already being employed in the treatment of breast cancer, Dr Kris notes, although, he cautions, “This is a step towards cure, rather than a full cure.”

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