According to the American Cancer Society, more than 235,000 Americans are estimated to be diagnosed with lung cancer in 2021. Among these people, the majority, about 80% to 85%, of the patients will be diagnosed with the type of lung cancer known as non–small-cell lung cancer (NSCLC).
Important advances in drug therapy have increased survival for patients with lung cancer, and for the first time, there are signs that death rates from lung cancer are coming down, although lung cancer remains the number 1 cause of cancer-related death in the United States.
The introduction of the new generations of targeted therapies and immunotherapies has led to significant improvements in outcomes for patients with lung cancer. However, until now, immunotherapies have been mainly used in patients with advanced or metastatic (stage IV) NSCLC that has spread to other parts of the body.
Unmet Need for Patients with Early-Stage NSCLC
Although immunotherapies, especially the PD-1 and PD-L1 inhibitors, have significantly extended the survival of patients with advanced or metastatic NSCLC until recently, they have not been available for patients with earlier-stage (stage I-III) lung cancer, whose cancer often continues to relapse (come back) after treatment and often progresses to metastatic (spreading) cancer.
“Up to 60% of patients with stage I-III NSCLC still experience disease relapse despite treatment with curative intent, demonstrating a high unmet medical need in this setting,” said Enriqueta Felip, MD, PhD, Head of the Lung Cancer Unit at Vall d’Hebron University Hospital in Barcelona, Spain, during the 2021 European Society for Medical Oncology (ESMO) Congress.
PD-1/PD-L1 Inhibitors in Advanced NSCLC
The majority of the PD-1 and PD-L1 inhibitors (or immunotherapies) have been approved for the treatment of patients with advanced or metastatic (stage IV) lung cancer, including Keytruda (pembrolizumab), Opdivo (nivolumab), Tecentriq (atezolizumab), and most recently, Libtayo (cemiplimab-rwlc).
Although the PD-L1 inhibitor Imfinzi (durvalumab) is approved for patients with stage III NSCLC, it is only approved for patients whose tumor cannot be removed by surgery (unresectable) and whose cancer has not progressed after concurrent radiation and chemotherapy.
In addition, Libtayo is also approved for earlier use in patients with locally advanced NSCLC who are not candidates for surgical removal of the tumor or for curative treatment with chemotherapy plus radiation.
Until very recently, no immunotherapy was approved for use in patients with early-stage lung cancer whose tumor was removed by surgery.
Benefits of Immunotherapy in Early Disease
Now, for the first time, the use of immunotherapy after surgical removal of the tumor and chemotherapy has shown benefits in patients with early-stage (stage IB-IIIA) NSCLC and PD-L1 expression.
In the recent study known as IMpower010, patients with early-stage NSCLC whose tumor had more than 1% PD-L1 expression on their tumor cells had shown benefit from the PD-L1 inhibitor Tecentriq, with the greatest benefit seen in patients with high (>50%) PD-L1 expression.
An interim analysis of the IMpower010 study previously demonstrated that treatment with Tecentriq after surgery and chemotherapy increased the time of disease-free survival (DFS) by 34% compared with best supportive care after surgery and chemotherapy.
Dr. Felip presented the results of an updated analysis at the latest ESMO Congress in early October, showing that in patients with PD-L1 expression of 1% or more, the use of Tecentriq increased the time of survival without signs of lung cancer compared with best supportive care.
“Atezolizumab [Tecentriq] is certainly stepping up as more effective therapy for this patient population,” Dr. Felip said.
IMpower010 compared the use of Tecentriq and best supportive care in 1,005 patients with early-stage (stage IB-IIIA) NSCLC after their tumor was removed by surgery, followed by up to 4 cycles of adjuvant (after surgery) chemotherapy.
Patients with high (≥50%) PD-L1 expression had the highest degree of benefit (34% improvement) from Tecentriq, which included reduction in disease recurrence (coming back) and death, and an intermediate benefit in patients with 1% to 49% PD-L1 expression. No benefit was seen in patients with NSCLC and no PD-L1 expression.
After an average follow-up of about 32 months, in almost half (44.7%) of the patients with stage IB-IIIA NSCLC and PD-L1 expression who received best supportive care the cancer came back, compared with a little more than one-quarter (29.4%) of the patients who received immunotherapy with Tecentriq.
The average time to the lung cancer coming back was 16.6 months in the patients who received Tecentriq compared with 10.9 months in the patients who received best supportive care.
“We are seeing results that will really move immunotherapy into early-stage disease,” said Antonio Passaro, MD, PhD, from the European Institute of Oncology in Milan, Italy, who commented on the study results at the ESMO meeting.
Dr. Passaro suggested that “The updated results from IMpower010 support the practice-changing outcomes from the interim DFS analysis and confirm the role of atezolizumab after adjuvant chemotherapy in patients with radically resected, early-stage NSCLC.”
“Results from this landmark study promise a potential paradigm shift in the treatment of patients with resected, early-stage NSCLC. They also shine important light on more effectively combating high-risk cancer in the early-stage setting before it spreads, as well as potentially preventing the disease recurrence,” concluded Dr. Felip.
New Treatment Approved for Early-Stage NSCLC
Based on these results, on October 15, 2021, the FDA accelerated the approval of Tecentriq for adjuvant treatment (after surgery and chemotherapy) of patients with early-stage (IB-IIIA) NSCLC and PD-L1 expression of 1% or more.
- Important advances in drug therapy have increased survival for patients with lung cancer
- Until now, immunotherapies have been mainly used in patients with advanced or metastatic (stage IV) NSCLC
- For the first time, the use of immunotherapy after surgical removal of the tumor and chemotherapy has shown benefits in patients with early-stage NSCLC and PD-L1 expression
- Results from this study promise a paradigm shift in the treatment of patients with resected, early-stage NSCLC
- Based on these results, in October, the FDA approved Tecentriq for adjuvant treatment of patients with early-stage NSCLC and PD-L1 expression