Menu

Determinants of Long-Term Response in Patients with NSCLC Treated with PD-1 Blockade

December 15, 2020 | Web Exclusives | Lung Cancer

Long-term responders were defined as patients with responses (partial response [PR] or complete response [CR]) lasting ≥24 months. Short-term responders were patients with PR or CR lasting <12 months. Researchers also compared these patients with patients who had progressive disease. PD-L1 expression was assessed by immunohistochemistry. Tumor mutation burden (TMB; defined as greater than or equal to the median of the cohort) was assessed by targeted next-generation sequencing.

Of 2382 patients, 6.3% (95% confidence interval [CI], 5.3%-7.4%) were long-term responders, with similar rates in both the Memorial Sloan Kettering Cancer Center (MSKCC) and Dana-Farber Cancer Institute (DFCI) cohorts. Short-term responses occurred in 6% of all patients. Long-term responders had a longer overall survival rate compared with short-term responders (median not reached vs 19.6 months; hazard ratio [HR], 0.07; P <.001 in the MSKCC cohort; median not reached vs 18.0 months; HR, 0.08; P <.001 in the DFCI cohort). Long-term responders had deeper responses compared with short-term responders (median best overall response, –73% vs –39%; P <.001).

Patients with long-term responses were also significantly more likely to be younger (<65 years old) with higher TMB (≥ median mutations per megabase) compared with both short-term responders and progressors. The rate of long-term response was enriched among patients with both high TMB and high PD-L1 compared with those with low TMB and low PD-L1 (16% vs 2%; P <.001).

Long-term response to PD-1 inhibition was achieved by 2% of patients with sensitizing EGFR mutations (N = 243). Loss of function variants in ARID1A (14% vs 2%), PTEN (8% vs 0%), and KEAP1 (12% vs 2%) were enriched in long-term responders compared with short-term responders (P <.05 for each). Patients with KRAS mutations and co-mutation with TP53 had a higher rate of long-term response compared with patients with KRAS mutations and co-mutation with STK11 (12% vs 2%; P = .01).

Researchers concluded that long-term response (ongoing response for ≥24 months) to PD-1 blockade is an uncommon but highly important clinical outcome in metastatic lung cancer. Younger age and high TMB correlate with long-term responders. The combination of high TMB and high PD-L1 enriches for long-term responders but not short-term responders. Features that predict long-term response may be distinct from those predicting initial response.

Reference

Luo J, Bandlamudi C, Ricciuti B, et al. Long-term responders to PD-1 blockade in patients with advanced non-small cell lung cancer. J Clin Oncol. 2020;38:suppl (abstract 9549).

Related Articles
New Low-Dose Computed Tomography (LDCT) Guidelines Expand Screening Opportunities
Rosie Kelly
April 5, 2021 | AONN+ Blog | Lung Cancer, News & Updates
The U.S. Preventive Services Task Force (USPSTF) updated their recommendations on qualifications for annual LDCT screens. Institutions should begin to prepare for an influx of patients due to the expansion in qualifications.
FDA Approves First Targeted Therapy for Metastatic NSCLC and MET Exon 14 Skipping
December 15, 2020 | Web Exclusives | Lung Cancer
Capmatinib Shows Activity in MET-Amplified Non–Small-Cell Lung Cancer
December 15, 2020 | Web Exclusives | Lung Cancer

Report Broken Links

Have you encountered a problem with a URL (link) on this page not working or displaying an error message?

Help us fix it! Report broken links here.

Report Broken Link

Thank You to Our Corporate Sponsors and Alliance Partners!

  • Patron Corporate Sponsor

    Patron Corporate Sponsor

  • Patron Corporate Sponsor

    Patron Corporate Sponsor

  • Patron Corporate Sponsor

    Patron Corporate Sponsor

  • Patron Corporate Sponsor

    Patron Corporate Sponsor

  • Patron Corporate Sponsor

    Patron Corporate Sponsor

  • Industry Relations Council Member

    Industry Relations
    Council Member

  • Industry Relations Council Member

    Industry Relations
    Council Member

  • Health System Partner

    Health System Partner

  • Health System Partner

    Health System Partner

  • Health System Partner

    Health System Partner