New treatments for localized and regional lung cancer 2022
New treatments for localized and regional lung cancer 2022
This year, a number of new treatments that have been established in distant lung cancer have been evaluated in combination with surgery for localized and regional lung cancer with impressive results leading to fast-track international approval for use.
Osimertinib [EGFR tyrosine kinase inhibitor] after lung cancer surgery
At the American Society of Clinical Oncology [ASCO] meeting in 2020, the use of osimertinib, a drug for patients whose cancers harboured EGFR gene mutations (approximately 5-20% varying by country) was presented showing a reduction in recurrent cancer and death after lung cancer surgery. The ADAURA study was conducted as an international multicentre clinical trial now published in the New England Journal of Medicine 2021[1] reporting (at 24 months) that participants who had a) complete lung cancer surgery for non-small cell lung cancer (within stage IB to IIIA) with b) an EGFR gene mutation who received c) osimertinib [given with or without chemotherapy] had 83% reduction in recurrent cancer or death. The study was stopped early due to overwhelming benefit, and [at the time of writing] is undergoing the licensing approval process in many countries worldwide. Critics of the results hold the view that the majority of the favourable outcome was due to the prevention of recurrent disease rather than death, and similar studies previously conducted that had great initial effects simply held back recurrent disease rather than “cure” cancer. Proponents argue that recurrence is an equally important quality of life outcome [it keeps patients out of the hospital so they can spend more time with family]. Some challenges are currently being faced by healthcare authorities evaluating the cost-effectiveness of new treatments, as their protocols and policies are based heavily on survival outcomes [for which the ADAURA trial has not yet gathered enough data due to stopping the trial early for ethical reasons]. At the time of writing osimertinib has received approval by FDA (US Food and Drug Administration), EMA (European Medicines Agency) and in the UK (from the cancer drugs fund).
Atezolizumab [immunotherapy] after lung cancer surgery
At ASCO 2021, the results of IMpower010 was presented reporting atezolizumab, an immunotherapy given after complete resection of stage II to IIIA non-small cell lung cancer followed by platinum based chemotherapy was associated with a 34% reduction in recurrence or death in patients whose cancers had more than 1% expression of a protein marker called PD-L1 (programmed death ligand 1 antigen). Critics of the results state concerns of multiple sub-group testing [to determine best fit rather than] with some uncertainty on any effect on overall survival in the study as a whole. Currently, atezolizumab has received licencing approval by FDA for use after surgery in patients who have completely resected non-small cell lung cancer in stage groups II to IIIA, who received platinum-based chemotherapy with more than 1% expression of PD-L1 in their cancers.
Nivolumab [immunotherapy] and chemotherapy before lung cancer surgery
At the American Association for Cancer Research (AACR) Annual Meeting 2021, the use of nivolumab and chemotherapy given before surgery yielded complete “pathologic” response in 24% of patients, meaning the cancer has completely responded to treatment in 24% without any trace left on microscopic examination of the removed lung. What was promising in their report was that the conduct, safety and extent of surgery were not affected by giving participants chemotherapy and immunotherapy before their operation. At the time of writing, there are no results on disease recurrence or survival, and the result of the trial Checkmate 816 are not yet published.
The author of the article Professor Eric Lim has received consultancy fees and/or project grants from AstraZeneca (who manufacture osimertinib), Roche (who manufacture atezolizumab) and Bristol Myers Squibb (who manufacture nivolumab).
Reference
[1] Wu YL, Tsuboi M, He J, John T, Grohe C, Majem M, Goldman JW, Laktionov K, Kim SW, Kato T, Vu HV, Lu S, Lee KY, Akewanlop C, Yu CJ, de Marinis F, Bonanno L, Domine M, Shepherd FA, Zeng L, Hodge R, Atasoy A, Rukazenkov Y, Herbst RS and Investigators A. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med. 2020;383:1711-1723.