ICIs Extend Survival in Older Patients With NSCLC, Brain Metastases

For older patients who have non–small cell lung cancer (NSCLC) with brain metastases at diagnosis, second-line chemotherapy following first-line chemotherapy was inadequate at producing a survival advantage compared with first-line chemotherapy followed by a second-line immune checkpoint inhibitor (ICI) regimen, according to study findings published in Translational Lung Cancer Research.¹

The study investigators evaluated outcomes from among patients 65 years and older by utilizing data from 2 linked databases: Surveillance, Epidemiology, and End Results (SEER) cancer registry (January 2010-December 2017) and Medicare enrollment and fee-for-service claims (January 2009-December 2019). They did this because few previous studies have investigated these outcomes among an older patient population with these diagnoses, and more information is needed on post–first-line therapies that can convey a survival advantage in older, more frail patients.

To be included in this investigation, all patients had to be 65 years and older and have continuous Medicare Part A/B coverage for at least 6 months before their diagnosis. They could not have a history of another lung cancer diagnosis or Medicare Part C coverage or be disenrolled from Medicare Part A/B from 6 months before diagnosis until the index treatment date. Patients were matched 1:1 to the chemotherapy group (n = 273; mean [SD] age, 71.25 [4.56] years) or the ICI group (n = 273; mean age, 72.11 [5.03] years). Most patients were female, White non-Hispanic, married, and lived in areas where 0% to less than 5%, 5% to less than 10%, or 10% to less than 20% lived below the federal poverty level.

Surveillance, Epidemiology, and End Results cancer registry (January 2010-December 2017) data and Medicare enrollment and fee-for-service claims (January 2009-December 2019) data were used for this study.| Image Credit: magicmike-stock.adobe.com

Lung, bone, or liver metastasis were not common at baseline diagnosis. However, the patients who received ICIs were more likely to have liver metastasis at diagnosis (20.15% vs 11.36%; P = .003). Squamous cell carcinoma was also more common in the ICI group (16.85% vs 9.16%; P = .009), while median time to second-or third-line treatment was similar:

• Second-line treatment: ICI group, 241 days vs chemotherapy group, 227 days (P = .29)
• Third-line treatment: 259 days vs 267, respectively (P = .80)

The ICI group also had a median follow-up that was longer than the chemotherapy group, at 206 (range, 2-1607) days vs 151 (range, 6-3240) days, and a longer median overall survival, at 209 (95% CI, 160-275) days vs 155 (95% CI, 135-187) days.

The authors then used a model that adjusted for subsequent ICI vs chemotherapy, age, married or not married status, female vs male, race, census tract poverty indicator level, nonmetropolitan area vs metropolitan area, bone metastasis vs no bone metastasis, liver metastasis vs no liver metastasis, lung metastasis vs no lung metastasis, Charlson Comorbidity Index, ECOG PS proxy 3 to 4 vs ECOG PS proxy 0 to 2, primary tumor grade and size, NSCLC histology, neurological resection within 1 year of diagnosis, and cranial radiation before index treatment date (no vs yes). With the robust sandwich method, they saw a 37% reduced risk of death with ICIs vs chemotherapy (HR, 0.63; 95% CI, 0.52-0.75), and with the MaxCombo method, the groups had a significant difference in survival times (P < .001).

Next, propensity score–matched analysis found that, again, the ICI treatment cohort had a longer median survival period compared with the chemotherapy cohort: 209 (95% CI, 161-284) days vs 152 (95% CI, 133-172) days. Further, a Cox regression analysis also determined an estimated 37% lower risk of death with ICIs (HR, 0.63; 95% CI, 0.52-0.76), and sensitivity analyses that excluded patients who did not undergo neoadjuvant cranial radiation before receiving ICI treatment also showed improved survival outcomes.

Speaking to their study’s strengths, the authors highlighted that although their findings echo previous research on the survival benefits of ICIs,^2-4 they improve upon them, too, because these newest results are for older patients who are typically underrepresented in clinical trials.¹ Also, even though their patients were an older age and considered frail, their data still indicate these patients with NSCLC and brain metastases can have improved survival with the appropriate treatment.

“These findings add to the evidence that ICIs likely confer a survival advantage in the second-line treatment of NSCLC over chemotherapy,” the authors concluded, “in older, more frail patients with brain metastases.”

References

1. Mahashabde RV, Bhatti SA, Martin BC, et al. Immune checkpoint inhibitors as subsequent treatment in older adults with non-small cell lung cancer and synchronous brain metastases. Transl Lung Cancer Res. 2024;13(7):1620-1634. doi:10.21037/tlcr-24-205

2. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627-1639. doi:10.1056/NEJMoa1507643

3. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540-1550. doi:10.1016/S0140-6736(15)01281-7

4. Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255-265. doi:10.1016/S0140-6736(16)32517-X