New treatments in advanced non-small cell lung cancer 2022
New treatments in advanced non-small cell lung cancer 2022
In recent years, we have learned more about the genetic changes that occur in lung cancer cells (known as somatic genetic alterations). Excitingly, more and more of these genetic alterations can now be treated with targeted treatments. Testing for these genetic alterations is now recommended for all patients with newly diagnosed non-small cell lung cancer.
Before 2021, FDA (US Food and Drug Administration) and EMA (European Medicines Agency) licensed a handful of targeted treatments against EGFR mutations (exon 19 deletion and L858R point mutations), ALK fusion, ROS1 fusion, BRAF V600E mutation, NTRK fusion and RET fusion.
Here’s an update on what happened since then…
Sotorasib for KRAS G12C mutation
KRAS G12C mutations are found in approximately 15% of all non-small cell lung cancers. At the World Conference on Lung Cancer in 2021, the results of the CODEBREAK100 trial were presented. Participants with advanced lung cancer containing KRAS G12C mutations who previously received chemotherapy and/or immunotherapy were given sotorasib with a overall response rate of 37% (cancer substantially shrunk in size or disappeared) and disease control rate of 81% (cancer responded or remained the same). The results are published[1] and has led to licensing approval by FDA and EMA for the use of sotorasib in patients with KRAS G12C mutation positive lung cancer who have previously received one form of systemic therapy (e.g. chemotherapy, immunotherapy).
Capmatinib and Tepotinib for MET exon 14 skipping
MET exon 14 skipping is found in approximately 2-4% of all non-small cell lung cancers.
Capmatinib was the first FDA approved medication (2020) for patients with MET exon 14 skipping positive non-small cell lung cancer based on the results of the published GEOMETRY trial [2]. In this trial, the overall response rate to capmatinib (where the cancer substantially shrunk in size or disappeared) was in 41% of patients who had previously received treatment for their lung cancer, and 68% of patients who have not previously received any treatment for their lung cancer.
At the 2020 American Society for Clinical Oncology (ASCO) annual meeting results from the VISION trial reported that the use of tepotinib in patients with MET exon 14 skipping positive NSCLC demonstrated an overall response rate (where the cancer substantially shrunk in size or disappeared) in 46% of participants. Unlike capmatinib, the response rate and median time to cancer growth was the same regardless of whether patients had previously received other cancer treatment or not. The result are published[3], and tepotinib received FDA licensing and MHRA approval for MET exon 14 skipping positive NSCLC in 2021, and is under review by EMA.
Amivantamab and mobocertinib for EGFR [exon 20 insertion]
EGFR exon 20 insertions make up approximately 10% of all EGFR mutations and are largely did not respond to standard EGFR targeted treatments (until now the main treatment for these cancers was chemotherapy). In 2021, the FDA approved two treatments for patients with EGFR exon 20 insertion positive NSCLC who have previously been treated with chemotherapy.
Firstly, at ASCO 2021, the CHRYSALIS trial was presented and now published[4] showing an overall response rate (where the cancer substantially shrunk in size or disappeared) with amivantamab in 40% of patients with EGFR exon 20 insertion. Amivantamab [currently FDA approved and awaiting EMA review] is given as an infusion which is generally well tolerated (most common side effects were rash and allergic-like reactions).
Likewise, the EXCLAIM trial of mobocertinib (given as a tablet) now published [5] reported an overall response rate (where the cancer substantially shrunk in size or disappeared) of 28%. Mobocertinib is FDA approved and under EMA review (at the time of writing) with common side effects of diarrhea, rash, nail changes, decreased appetite and nausea.
Never has there been a more exciting time for development of new and very effective drugs for advanced lung cancer.
The author of the article Dr Wanda Cui has received funding from Janssen that manufactures amivantamab.
References
[1] Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, Kato T, Curioni-Fontecedro A, Sacher A, Spira A, Ramalingam SS, Takahashi T, Besse B, Anderson A, Ang A, Tran Q, Mather O, Henary H, Ngarmchamnanrith G, Friberg G, Velcheti V and Govindan R. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. New England Journal of Medicine. 2021;384:2371-2381.
[2] Wolf J, Seto T, Han J-Y, Reguart N, Garon EB, Groen HJM, Tan DSW, Hida T, de Jonge M, Orlov SV, Smit EF, Souquet P-J, Vansteenkiste J, Hochmair M, Felip E, Nishio M, Thomas M, Ohashi K, Toyozawa R, Overbeck TR, de Marinis F, Kim T-M, Laack E, Robeva A, Le Mouhaer S, Waldron-Lynch M, Sankaran B, Balbin OA, Cui X, Giovannini M, Akimov M and Heist RS. Capmatinib in MET Exon 14–Mutated or MET-Amplified Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2020;383:944-957.
[3] Paik PK, Felip E, Veillon R, Sakai H, Cortot AB, Garassino MC, Mazieres J, Viteri S, Senellart H, Van Meerbeeck J, Raskin J, Reinmuth N, Conte P, Kowalski D, Cho BC, Patel JD, Horn L, Griesinger F, Han J-Y, Kim Y-C, Chang G-C, Tsai C-L, Yang JC-H, Chen Y-M, Smit EF, van der Wekken AJ, Kato T, Juraeva D, Stroh C, Bruns R, Straub J, Johne A, Scheele J, Heymach JV and Le X. Tepotinib in Non–Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. New England Journal of Medicine. 2020;383:931-943.
[4] Park K, Haura EB, Leighl NB, Mitchell P, Shu CA, Girard N, Viteri S, Han JY, Kim SW, Lee CK, Sabari JK, Spira AI, Yang TY, Kim DW, Lee KH, Sanborn RE, Trigo J, Goto K, Lee JS, Yang JC, Govindan R, Bauml JM, Garrido P, Krebs MG, Reckamp KL, Xie J, Curtin JC, Haddish-Berhane N, Roshak A, Millington D, Lorenzini P, Thayu M, Knoblauch RE and Cho BC. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J Clin Oncol. 2021;39:3391-3402.
[5] Zhou C, Ramalingam SS, Kim TM, Kim S-W, Yang JC-H, Riely GJ, Mekhail T, Nguyen D, Garcia Campelo MR, Felip E, Vincent S, Jin S, Griffin C, Bunn V, Lin J, Lin HM, Mehta M and Jänne PA. Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial. JAMA Oncology. 2021:e214761-e214761.