EGFR, an important target for targeted therapy in non-small cell lung cancer (NSCLC), is mutated at a high frequency in Asian populations, and the treatment model of first-line EGFR TKIs + second-line chemotherapy has become the standard of care for patients with advanced NSCLC with EGFR-sensitive mutations. However, due to physical status, drug toxicity and personal wishes, some patients still do not receive second-line chemotherapy, which affects the overall survival. How to delay the onset of resistance to EGFR TKIs and optimize treatment regimens to maximize the efficacy of first-line therapy and prolong survival has always been a clinical concern, and the main strategies currently include combining EGFR TKIs with other drugs, such as combining TKIs with chemotherapeutic drugs with synergistic effects, combining TKIs with targeted drugs with other mechanisms of action (bevacizumab, Tivantinib, etc.); in addition, attempts have been made to address these issues through the development of third-generation EGFR TKIs and new target agents. The JMIT study was designed in 2011, shortly after the dominance of EGFR TKIs in the first-line treatment of advanced NSCLC with EGFR-sensitive mutations was established, and it is clinically important to explore how to “add to the mix” of TKIs to prolong patient survival. Pemetrexed, as the preferred drug for advanced non-squamous cancer treatment, has a lower toxicity profile and better clinical tolerability than other chemotherapeutic agents, and the combination of chemotherapeutic agents such as pemetrexed and EGFR-TKI has been shown to produce synergistic effects in preclinical settings, making it a more suitable drug choice for combination therapy. For these reasons, the JMIT study was conducted in an East Asian population to improve the efficacy of first-line therapy for patients with advanced NSCLC with EGFR-sensitive mutations. The JMIT study is a randomized, multicenter, open, parallel-controlled phase II study in an East Asian population. The primary objective was to assess whether gefitinib + pemetrexed prolongs PFS versus gefitinib monotherapy in patients with EGFR mutations in first-line treatment. secondary observational endpoints included OS, ORR, DCR, Qol, and safety. Patients enrolled were primary, EGFR-sensitive mutant stage IV non-squamous NSCLC patients with ECOG PS 0-1, randomly assigned in a 2:1 ratio to the gefitinib (250 mg/d) + pemetrexed (500 mg/m2,q3w) arm (G+P) and the gefitinib (250 mg/d) monotherapy arm (G), and treatment in both arms proceeded until the onset of disease progression or intolerable tolerated toxicity. From February 2012 to August 2013, 191 patients were enrolled, 126 in the G+P group and 65 in the G group. median PFS was significantly prolonged by nearly 5 months in the G+P combination group relative to the G monotherapy group (15.8m vs 10.9m, HR=0.68, 95% CI 0.48-0.96, P=0.029), with a significant 32% reduction in the risk of disease progression. Subgroup analysis of PFS showed that almost all subgroups, including the subgroup of common EGFR mutant subtypes (exon 19, 21 mutations), consistently showed a PFS benefit in the G+P group. In addition ORR was comparable in both groups, while DOR was prolonged by 4.1 months in the combination therapy group compared to the single agent group. These results suggest that combination pemetrexed treatment may delay the onset of drug resistance, possibly related to a synergistic effect between the two drugs, and that relevant biomarker studies are needed to further interpret the mechanism of combination therapy. In addition, whether this PFS benefit can eventually be converted to an OS benefit is a key question in our assessment of whether combination therapy can provide a survival benefit, and the OS results are not yet mature, so let us wait and see. In terms of safety, the incidence of grade 3/4 drug-related TEAEs was increased in the combination group compared with the single-agent group (42.1% vs. 18.5%); the incidence of SAEs was 8.7% vs. 1.5%, respectively; the proportion of patients discontinuing due to TEAEs was slightly increased in the combination group compared with the single-agent group, 16.7% and 9.2%, respectively; however, there was no significant difference in lethal drug-related AEs between the two groups Overall, combination therapy resulted in only grade 1/2 anemia, nausea, vomiting, malaise, and elevated transaminases, with no subsequent increase in rash, diarrhea, or interstitial pneumonia associated with TKIs, and thus remained clinically manageable and well tolerated. How to maximize the benefit of first-line therapy for patients remains a concern for clinicians in recent years. From non-selective to selective populations and from first-line to second-line therapy, many attempts have been made in the field of combination applications of EGFR TKIs and chemotherapy, with the expectation that they can further significantly delay the onset of disease progression or resistance and translate into clinically meaningful survival benefits, thus changing clinical practice. At present, there is still no consensus on the optimal mode of combination application, and the INTACT, TRIBUTE, and TALENT studies of targeted synchronous chemotherapy modalities conducted in earlier years failed to yield positive results due to enrollment of non-selected populations, although survival benefit was observed for either the maintenance treatment mode of switching (SATURN) or the interposition treatment mode (FASTACT-II), but the 2014 The NEJ005 study published by ASCO confirmed the superiority of synchronous combination therapy over sequential treatment modalities for patients with advanced NSCLC with EGFR mutations, and therefore a phase III clinical study of synchronous combination therapy versus single-agent targeted therapy was conducted (NEJ009), suggesting that synchronous combination therapy modalities may be a better option to improve the benefit of first-line therapy. The JMIT study was conducted in an East Asian population with high-frequency mutations in EGFR, and further explored the simultaneous combination of targeted agents and chemotherapy. Although the OS is not yet mature, the PFS of pemetrexed in combination with gefitinib was 15.8 months, which resulted in an improvement of PFS of nearly 5 months compared to gefitinib alone, and did not significantly increase the incidence of adverse events, which is important for EGFR -sensitive mutation patients has greater guidance for the choice of first-line treatment strategy, and the follow-up report of OS data is also expected. In addition, the choice of the best partner for EGFR TKIs in combination therapy modality needs to be carefully considered. The PFS of the A+T treatment mode in the JO25567 study was 16.0 months, which was close to that of the JMIT study, but pemetrexed was more advantageous in terms of both the incidence of adverse events and the efficacy ratio. Although the design of the JMIT study was similar to that of the NEJ009 study, the JMIT study did not combine platinum drugs because, on the one hand, some preclinical studies showed that the direct combination of EGFR-TKIs and platinum may have antagonistic effects, and, on the other hand, the combination of platinum drugs may increase the survival benefit and toxicity associated with the treatment. On the other hand, the combination of platinum may increase the toxicity of the treatment, and it is still worth exploring whether to use targeted combination of platinum-containing chemotherapy in future clinical applications.