Lung cancer survival saw more than three-fold increase in the past 10 years
Since the advent of immunotherapy, a more than three-fold increase in median overall survival (OS) has been seen in lung cancer patients over the past 10 years, according to data presented at the Advances in Medicine 2019 conference organized by the Chinese University of Hong Kong (CUHK).
“We have come a long way since more than 10 years ago, from a median OS of 10 months with chemotherapy to 34.1 months with later-generation immunotherapy,” said Professor Tony Mok of the Department of Clinical Oncology, CUHK. [N Engl J Med 2002; 346:92-98; J Clin Oncol 2018;36:2244-2250]
“The limited efficacy of chemotherapy in lung cancer led to the discovery of biomarkers such as driver oncogenes. Interestingly, these oncologic drivers are dissimilar between Asians and Westerners. KRAS mutations predominate in the Western population, whereas EGFR mutations are more common among Asian patients,” he added.
The phase III, open-label IPASS study was among the first study to demonstrate that the use of the tyrosine kinase inhibitor (TKI) gefitinib resulted in longer progression-free survival (PFS) vs chemotherapy in EGFR mutation-positive patients (hazard ratio [HR], 0.48; 95 percent confidence interval [CI], 0.36 to 0.64; p<0.001). [N Engl J Med 2009;361:947-957]
“The ASPIRATION study demonstrated that treatment with immunotherapy [ie, erlotinib] beyond progression among EGFR mutation-positive non-small-cell-lung cancer [NSCLC] patients is feasible and may delay salvage therapy in selected patients,” added Mok. [JAMA Oncol 2016;2:305-312]
“The IMPRESS study demonstrated that chemotherapy is a better option in patients with disease progression after first-line gefitinib therapy. A combination of immunotherapy and chemotherapy is not advisable and would result in detrimental effects,” explained Mok. [J Clin Oncol 2017;35:4027-4034]
The ARCHER 1050 study showed that patients treated with the second-generation TKI dacomitinib achieved better median PFS (14.7 months vs 9.2 months; p<0.0001) and OS (34.1 months vs 26.8 months; p=0.0438) vs those treated with the first-generation TKI gefitinib. [Lancet Oncol 2017;18:1454-1466]
Resistance to TKIs are mostly attributed to T790M mutations. The AURA 3 study showed better median PFS with osimertinib among patients with EGFR TKI resistance vs chemotherapy (10.1 months vs 4.4 months; p<0.001). [N Engl J Med 2017;376:629-640]
ALK gene rearrangement results in the formation of a fusion protein that serves as a driver oncogene. The PROFILE 1014 study showed that crizotinib treatment among ALK-positive lung cancer patients provided better OS (median, not reached vs 47.5 months; p=0.0489) vs chemotherapy. [Ann Oncol 2017;28:v605-v649]
“This data showed us that patients can survive for at least 4 years whether they are given chemotherapy or TKI treatment,” commented Mok.
Treatment of patients with ROS-1 and RET rearrangements with crizotinib and LOXO-292, respectively, has shown benefits in terms of OS and response rates. [Ann Oncol 2019, doi: 10.1093/annonc/mdz131; J Clin Oncol 2018;36(15 suppl): 102-102]
“These two studies demonstrated the concept of personalized medicine, where treatment depends on genetic variations of the patient,” Mok said.
“The most recent developments in the field include the use of CRISPR-Cas9 technology for editing T lymphocytes with PD-1 aberrations and targeting the microenvironment as a strategy for lung cancer treatment,” he added.