Histologic transformation of epidermal growth factor receptor–mutated lung cancer

Histologic transformation in lung cancer: when one door shuts, another opens

“…An OS of 9–15 months from the time of HT diagnosis has been reported in previous literature. 10 , 119 – 121 Moreover, the OS and PFS of HTs to SCLC were comparable with those of de novo SCLC. 122 , 123 From the perspective of disease behavior, one previous report suggested that HT to SCLC in patients with EGFR mutation-positive NSCLC might be more aggressive than in patients without EGFR -mutation because the median time to HT for patients with EGFR -mutation was significantly shorter than that for patients without EGFR -mutation.…”

“…Our largest cohort study reported among 2624 re-biopsy cases that the prevalence of HTs to HGNEC was 2.2% while that to other types of NSCLC was 0.6%. 10 Overall, the time from initial diagnosis of HT to HGNEC ranged from 13 to 22 months. Four cohort studies reported that most cases included the first or second G EGFR-TKIs, and HT after the third G TKI therapy.…”

“…Although uncommon, HTs from one subtype of NSCLC to another have been reported in 0.6% of in patients with lung cancer. 10 Most of the reports were case reports or small case series. In our previous cohort study, most TKIs that were used during HTs were first or second generation.…”

“… 125 For patients with HTs to another subtype of NSCLC, the OS was reported to be 12.1 months. 10 However, the data of survival outcomes of patients with HTs to SqCC were limited compared with that of patients with HTs to SCLC. Moreover, no study has yet compared OS from the time of diagnosis between HT and non-HT cases; therefore, the clinical impact of HTs should be investigated in future studies.…”

“… 105 Specifically, in our study, the total objective response rate and disease control rate of ICI therapy (PD-1/PD-L1 inhibitor monotherapy or platinum-pemetrexed combined with PD-1/PD-L1 inhibitors) were 0% and 17%, respectively, and the median PFS was 2.0 months. 10 Another large-scale report showed that no responses were observed after HTs in 17 patients who received ICIs, either as a single-agent PD-1 or PD-L1 inhibitor ( n = 9) or as part of a combination ipilimumab–nivolumab regimen ( n = 8). 119 None of the 17 patients derived clinical benefits from these therapies, as the longest time to progression was only 9 weeks.…”