Efficacy of chemotherapy in epidermal growth factor receptor (EGFR) mutated metastatic pulmonary adenocarcinoma patients who had acquired resistance to first-line EGFR tyrosine kinase inhibitor (TKI)

Abstract

Pemetrexed-based combination chemotherapy is preferred before a more efficient treatment strategy is found.

Pemetrexed had significantly better clinical efficacy in patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving platinum-based chemotherapy after developing resistance to the first-line gefitinib treatment

“…Recently, some studies enrolled patients who had tumors with EGFR mutation and received EGFR -TKI as the first-line therapy. Tseng et al 11 indicated that using cytotoxic chemotherapy as the second-line therapy resulted in a median PFS of 4.5 months and OS of 14.6 months. Similarly, this study showed that patients treated with cytotoxic chemotherapy as the second-line treatment after gefitinib failure had a median PFS of 4.3 months and OS of 14.6 months.…”

“… 25 Indeed, Park et al 19 recently showed that pemetrexed used alone as a salvage drug after gefitinib failure provided significantly longer PPS than platinum-based doublet chemotherapy did (PFS: 4.2 months vs 2.7 months, P =0.008). Tseng et al 11 also demonstrated that chemotherapy with pemetrexed as the second-line chemotherapy for patients having acquired resistance to the first-line EGFR -TKI seemed to provide better PFS (4.7 months vs 3.3 months, P =0.62) and better OS (15.1 months vs 8.1 months, P =0.17) than chemotherapy without pemetrexed did, but the differences were nonsignificant and inconclusive. In our study population, chemotherapy with pemetrexed was associated with a significantly longer PFS and OS in patients with stage IV lung adenocarcinoma receiving salvage chemotherapy as the second-line treatment after gefitinib failure (data not shown).…”

Efficacy of pemetrexed-based regimens in advanced non–small cell lung cancer patients with activating epidermal growth factor receptor mutations after tyrosine kinase inhibitor failure: a systematic review

“…In two studies, 1 , 16 pemetrexed-based chemotherapy significantly extended PFS in EGFR -mutant NSCLC patients who failed first-line treatment with EGFR -TKIs (Park et al 1 : hazard ratio [HR] [95% CI] = 0.54 [0.34, 0.86], p =0.009; Yang et al 16 : 0.47 [0.26, 0.84], p =0.0101). Furthermore, Tseng et al 17 showed numerically longer PFS in NSCLC patients treated with pem regimens (median 4.7 months) compared to non-pem regimens (median 3.3 months). Overall, the weighted median PFS was numerically longer in patients treated with pemetrexed (5.09 months) than in patients receiving non-pem regimens (3.23 months; Table 2 ).…”

“…Pemetrexed – either alone or in combination with other chemotherapy regimens – was effective among NSCLC patients with EGFR mutations who experienced resistance or disease progression after failure of EGFR -TKI treatment, with PFS ranging from 2.7 to 6.4 months and a weighted median PFS of 5.09 months ( Table 2 ). Three studies 1 , 16 , 17 directly compared the PFS data of pem regimens (n=148) versus non-pem regimens (n=97) in NSCLC patients with EGFR mutations who experienced resistance or disease progression after failure of EGFR -TKI treatment ( Table 2 ). In all three studies, median PFS was longer for the pem regimens as compared to the non-pem regimens ( Table 2 ).…”

The resistance mechanisms and treatment strategies for EGFR-mutant advanced non-small-cell lung cancer

“…As histological transformation to small-cell lung carcinoma occurs during active treatment with targeted therapy, in dynamic progression it is recommended to do biopsy to capture these histological and phenotypic changes as this could impact the chemotherapy options [ 38 , 74 – 75 ]. Few studies suggest to continue chemotherapy after patients acquiring resistance [ 76 , 77 ]. Kuo et al reported higher remission rate (48.7% vs 21.4%), longer medium PFS (5.1 months vs 1.8 months) and medium OS (12.7 months vs 7 months) after receiving taxane-based chemotherapy than patients in nontaxane regimen [ 76 ] IMPRESS, a phase 3 randomized trial showed that progression-free survival was not prolonged in patients on continuation of gefitinib after disease progression compared to platinum-based doublet chemotherapy suggesting the later to be an gold-standard in such settings [ 78 ].…”