Abstract 27P
Background
Platinum(pt)-based chemotherapy (CTx) is the current standard treatment option in patients (pts) with EGFR mutant NSCLC who progress on osimertinib (osi). However, outcomes with CTx are dismal and CNS disease is an unmet need in this setting.
Methods
Pts with EGFR mutant NSCLC who were candidate to receive osi in the metastatic setting at our center from 2015 to 2022 were retrospectively evaluated to identify pts who received standard pt-based CTx post-osi. Data were collected on outcomes to standard CTx with focus on brain metastases and progression patterns.
Results
220 pts received indication for osi in the study period, n=181 had adequate follow up data. Overall, 110 pts experienced disease progression on osi. Median time to osi PD was 43 months (95% CI 37-63). Of them, 55 patients (50%) had no access to further treatment lines because of death. Of the remaining 55 pts, 10 received experimental treatments in clinical trials, whereas 45 received standard pt-based CTx and were considered for this study. Median duration of CTx was 3 months (95% CI 2-5), best responses among 40 pts evaluable were observed as following: 15% PR/CR, 45% SD, 40% PD. Median PFS and OS were 3 (95% CI 2-4) and 10 (95% CI 6-15) months, respectively. All patients had baseline and follow up brain radiologic assessment (n=29 CT scan, n=16 MRI), 18 had baseline brain metastases at the time of CTx start, 4 received previous brain RT for CNS oligo-PD on osimertinib. With a median follow-up of 9 months, intracranial PD occurred in 12 (30%) pts (67% among those with baseline CNS metastases), being the first site of PD in 75% of cases, symptomatic in 42%. Median time for IC PD was 2 months (95% CI 1-NA). IC PD occurred as oligometastatic PD in 42%, whereas in 58% of cases it was associated with systemic PD. The preferred approaches to treat IC PD were SBRT (16%), WBRT (16%), new systemic treatment (42%), BSC (25%).
Conclusions
CNS-progression is confirmed as an unmet need in EGFR mutant NSCLC pts. Clinical and CNS-specific outcomes in pts receiving standard CTx after failure of osi are disappointing. Novel treatment options with demonstrated better CNS outcomes may help in addressing this important issue.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
I. Attili: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb. A. Passaro: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, eCancer; Financial Interests, Institutional, Invited Speaker, Steering Committee Member PALOMA-3 trial: Janssen; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Janssen; Non-Financial Interests, Personal, Other, Scientific Commitee for Lung Cancer Guideline: AIOM; Non-Financial Interests, Personal, Officer, ESMO Council Member & Chair of Communication Committee: ESMO. F. de Marinis: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Roche; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Pfizer, Novartis, Takeda, Xcovery. All other authors have declared no conflicts of interest.