Chemotherapy and immunotherapy before lung cancer surgery
Chemotherapy and immunotherapy before lung cancer surgery
In 2022, the results of a major study were published [Forde et al NEJM 2022] looking at the impact of adding immunotherapy to chemotherapy before routine lung cancer surgery. In this study, participants had to have a locally advanced, surgically removable tumor and were assigned to receive either nivolumab (immunotherapy) and chemotherapy or chemotherapy alone. Those who received the combination of immunotherapy and chemotherapy were 14 times more likely to have complete eradication of tumor (confirmed on removal of the cancer by surgery) and much more likely (approximately double the chance) to be alive without evidence of disease at 2 years from the time of diagnosis. These improvements in survival resulting from the addition of immunotherapy to chemotherapy before surgery were observed without any increased serious side effects from treatment, risk from surgery or impairment to quality of life compared to chemotherapy alone before surgery.
This study (CheckMate 816) represents one of the most significant advancements in the care of patients with early-stage lung cancer in the last 20 years. Prior to this, chemotherapy given before surgery had around a 20% improvement in survival [Lim et al JTO 2009] and most doctors offered it after surgery in patients with lymph nodes that were infiltrated with cancer. One downside of chemotherapy offered after surgery was that many patients (for numerous reasons) did not choose to have it and therefore did not have the chance to benefit.[Lim VIOLET NEJM Evidence 2022] In CheckMate 816, 94% of patients were able to complete all chemotherapy and immunotherapy treatments however, 17% did not proceed to their operation, either due to a change in patient or treating team decision or due to cancer progression. Arguably, patients whose cancer progresses on such highly active treatments are unlikely to benefit from the risks of surgery and are better suited to other less invasive types of therapy.
More recently, a national study called NADIM 2, run in highly experienced treatment centers in Spain, demonstrated that pre-operative chemotherapy and immunotherapy resulted in only 7% of patients not progressing to surgery [Provencio et al, WCLC, 2022], suggesting that treating team experience with these approaches is of importance to patient outcomes. The NADIM 2 study also demonstrated the ability to achieve more operations where all evidence of cancer was removed in those who received chemotherapy and immunotherapy and a more than 20% absolute increase in overall survival at 2 years.
With these results, oncologists and surgeons around the world are offering the option of immunotherapy and chemotherapy before surgery. Currently, the regimen is approved by the FDA in and Health Canada, with pending approvals in Europe and UK.
Consider discussing this option with your surgeon to see if would qualify for this treatment that may be offered to patients in stage IB to IIIB early-stage lung cancer that can be completely removed by an operation.
January 2023
Dr Spicer was a co-author of the CheckMate 816 trial, and has received funding support from Bristol Meyers Squibb, the company that manufactures nivolumab. Dr. Spicer has received honoraria for consultancy and speaking engagements from Merck, AstraZeneca, Regeneron, Novartis, Roche, Protalix Biotherapeutics, Xenetic Biosciences, Chemocentryx and Amgen. He has also received research funding to his institution, the McGill University Health Center Research Institute from AstraZeneca, Roche, Merck, CLS Therapeutics and Protalix Biotherapeutics. Dr. Spicer has clinical trial leadership roles for trials involving BMS, Novartis, Roche, Merck and AstraZeneca.
