By Kevin K. Patel, MD
Recent advances in targeted therapy and immunotherapy are improving outcomes in patients with resectable non-small cell lung cancer (NSCLC), an aggressive disease with a stubbornly high mortality rate.
One in 16 Americans will be diagnosed with lung cancer in their lifetime, the majority at an advanced stage. Many patients with advanced NSCLC have multiple co-morbidities and a history of heavy smoking that affect their ability to tolerate systemic therapies.
Few patients with NSCLC have pathologic stage 1 or stage 2 disease when diagnosed. Resected stage 1A and low-risk stage 1B patients with negative margins do not require adjuvant therapy.
On the other hand, it is recommended that patients with resected high-risk stage 1B cancer – defined as a lung tumor size greater than 4cm and/or poorly-differentiated cancers – or stage 2 or stage 3A disease undergo four cycles of platinum-based doublet chemotherapy.
These NSCLC patients remain at a substantial risk of cancer recurrence even after resection and chemotherapy, with a low five-year survival rate compared to other solid organ cancer patients diagnosed at similar stages.
Yet, recent randomized clinical trials have shown promising results for both tyrosine kinase inhibitor-based (TKI) oral therapies and immunotherapy.
In the ADAURA trial, for example, patients with resected stage 1B to 3A cancer plus an EGFR mutation were randomized to receive up to three years of oral targeted Osimertinib therapy versus placebo. Disease-free survival relative to placebo improved from 52 percent to 89 percent, with a hazard ratio of 0.2; patients had an 80 percent reduced chance of dying as a result of receiving adjuvant Osimertinib therapy.
Another new medication, Alectinib, has targeted resected stage 1B to 3A patients with ALK-positive NSCLC. In trials, patients who received two years of this adjuvant therapy versus four cycles of platinum-based chemotherapy had a higher rate of disease-free survival at two years – 94 percent compared to 64 percent, with a hazard ratio of 0.24 percent – and a 76 percent reduced risk of dying.
Moreover, the use of immunotherapy is rising in the neoadjuvant and perioperative settings due to positive incoming data.
The Keynote-091 trial compared Pembrolizumab, a checkpoint inhibitor, to placebo as an adjuvant therapy for stage 1B to 3A disease without an EGFR or ALK mutation. Adding one year of adjuvant Pembrolizumab immunotherapy after four cycles of adjuvant platinum-based doublet chemotherapy increased disease-free survival from 42 to 54 months.
Another trial, Checkmate 816, targeted patients with high-risk stage 1B to stage 3 resectable NSCLC without an EGFR or ALK mutation. Pathologic complete response increased from 2.2 percent in the study’s chemotherapy-only group to 24 percent with the addition of just three doses of Nivolumab to neoadjuvant platinum-doublet chemotherapy.
Similarly, the Keynote-671 trial found benefit in adding four cycles of Pembrolizumab to neoadjuvant platinum-based chemotherapy, followed by adjuvant Pembrolizumab for up to 13 cycles, in patients with resectable stage 2 to 3B cancer. Those patients had an improved event-free survival of 62 percent at two years, compared to 41 percent with chemotherapy alone.
We expect many more such advances in the near future. Therefore, we encourage quick referral to a specialist for all patients with suspected early-stage lung cancer.
Dr. Patel is a Medical Oncologist and Hematologist with Virginia Oncology Associates, based in Suffolk. virginiacancer.com
