Checkpoint inhibitors, second-line nab-paclitaxel effective for older adults with non-small cell lung cancer
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Two treatment regimens showed efficacy as second-line therapy for older adults with non-small cell lung cancer, according to results of separate studies published in Cancer.
Although clinical trials have demonstrated the effectiveness of new first-line treatment regimens for this patient population, second-line treatment remains an area of investigation.
Consistent with prior research, results of the first study showed single-agent nab-paclitaxel (Abraxane, Celgene) appeared safe and effective as second-line treatment among older adults with NSCLC. In the second study, the immune checkpoint inhibitors nivolumab (Opdivo, Bristol-Myers Squibb) or pembrolizumab (Keytruda, Merck) appeared effective for older patients with conserved performance status.
Nab-paclitaxel
“Previous research has shown that fit older adults benefit from the same treatments as younger patients as first-line therapy for stage IV NSCLC. Despite these data, therapeutic nihilism remained regarding second-line options,” Jared M. Weiss, MD, oncologist in the department of hematology and oncology at UNC Lineberger Comprehensive Cancer Center, told Healio. “The philosophical goal of this research was to show that fit, older patients could benefit from second-line therapy just like younger patients. The choice of nab-paclitaxel was driven by data published by Socinski and colleagues that showed nab-paclitaxel may be more effective in older patients.”
The phase 2 clinical trial included 42 patients (mean age, 76 years; range, 71-84) with NSCLC previously treated with a platinum doublet regimen. The researchers did not exclude patients who received a PD-1 inhibitor.
Grade 3 to grade 5 toxicities served as primary endpoint.
Researchers assessed response rate, PFS, OS and associations between baseline sarcopenia and outcomes, as well as changes in T lymphocyte p16 before and during treatment. They also conducted geriatric assessments before and during treatment.
Overall, 33.7% of patients experienced grade 3 to grade 5 toxicities, including decreased white blood cell count (11.9%), neutropenia (9.5%) and fatigue (11.9%). One patient died after developing an infection that led to sepsis.
Nab-paclitaxel conferred an overall response rate of 34.2%, including a complete response rate of 2.6% and a partial response rate of 31.6%. In addition, 39.5% of patients achieved stable disease, corresponding to a disease control rate of 73.7%.
Median PFS was 5.2 months and median OS was 9.3 months.
Geriatric assessment results showed 42% of patients were frail, 39% were prefrail, 21% had an ECOG performance status of 2 and 27% were sarcopenic. The investigators found frailty to be the only factor predictive of inferior survival (median OS, 7.5 months vs. 14.2 months; P = .045). Moreover, patients with progressive disease had the lowest levels of baseline lymphocyte p16 (P = .02).
Results of a retrospective subgroup analysis that included 19 older patients who received nab-paclitaxel as part of a larger randomized trial showed a response rate of 15.8% (95% CI, 3.5-39.6), median PFS of 4.2 months (95% CI, 2.6-5.1) and median OS of 13.6 months (95% CI, 5.3 to not reached).
“Fit, older patients tolerate and benefit from second-line cytotoxic therapy just like younger patients, and chronologic age alone should not be used to exclude patients from this option,” Weiss told Healio. “Nab-paclitaxel is a particularly promising agent in this context.”
The trial conducted by Weiss and colleagues is important and notable for two main reasons, according to an editorial accompanying both studies by Charu Aggarwal, MD, MPH, Leslye M. Heisler assistant professor for lung cancer excellence at Perelman School of Medicine at University of Pennsylvania, and a HemOnc Today Editorial Board Member, and Corey J. Langer, MD, director of thoracic oncology and professor of medicine at the Hospital of the University of Pennsylvania.
“First, it demonstrated the feasibility of conducting a well-designed, elderly specific trial that allowed for the inclusion of frail patients, including patients with an ECOG performance status of 2,” they wrote. “Second, it demonstrated that nab-paclitaxel is a viable, efficacious, safe and well-tolerated option for second-line therapy in the elderly, especially for taxane-naive patients.”
Immune checkpoint inhibitors
In the second trial, Bora Youn, PhD, researcher in the department of health services, policy and practice at Brown University, and colleagues aimed to examine the real-world effectiveness of immune checkpoint inhibitors among older adults with advanced NSCLC.
“Older adults constitute the majority of patients with advanced cancer, yet are significantly underrepresented in clinical trials,” Youn told Healio. “Immune checkpoint inhibitors are among the most commonly used novel cancer therapies, and we sought to assess their effectiveness in this underrepresented population of patients.”
Researchers pooled data from the SEER database on 1,256 patients (median age, 75.3 years; 8.4% age 85 years) diagnosed with stage I to stage IV NSCLC between 2002 and 2015. The majority of patients (92%) received nivolumab, and 8% received pembrolizumab. Youn and colleagues assessed patient characteristics and OS from initiation of checkpoint inhibitors in 2016 through Dec. 31, 2017.
Median time from diagnosis to inhibitor initiation was 14.1 months for nivolumab and 19.3 months for pembrolizumab.
A considerable proportion of patients (42.6%) were initially diagnosed with stage IV NSCLC, and nearly half (48.7%) had two or more comorbid conditions. Researchers used a claims-based proxy and found that 11.5% of patients had poor performance status and 12.6% of patients had a history of autoimmune conditions.
Median OS after initiation of inhibitor therapy was 9.3 months (95% CI, 8.5-10.5), the 1-year survival rate was 43% (95% CI, 40.2-45.7) and the probability of 18-month survival was 31.3% (95% CI, 28.5-34.1).
Results of multivariable analyses suggested factors associated with an increased risk for death included multiple comorbid conditions, squamous histology, a history of nonplatinum doublet systemic therapy, recent radiotherapy and shorter time from initial diagnosis to treatment initiation. Factors not associated with an increased risk for death included demographics, poor performance status and prior autoimmune conditions.
Limitations of the study included the fact that most patients received nivolumab, regardless of PD-L1 expression, and the analysis reflects practice patterns during the study period.
“Our findings suggest that immune checkpoint inhibitors can be offered to older adults with conserved performance status, and treatment decision should not be based solely on age or comorbid condition,” Youn told Healio. “We plan to continue to work on projects that aim to understand the real-world clinical and financial impact of these treatments.”
These results appear favorable and are similar to those expected with immunotherapy for younger patients, Aggarwal and Langer wrote in the accompanying editorial.
“The articles by Youn [and colleagues] and Weiss [and colleagues] ... have confirmed that there is no longer room for therapeutic nihilism in the management of older adults,” they wrote. “Fit, elderly patients with preserved ECOG performance status should be treated with standard-of-care therapies similar to their younger counterparts.” – by Jennifer Southall
For more information:
Jared M. Weiss, MD, can be reached at the The University of North Carolina at Chapel Hill, 170 Manning Drive, Room 3115, Campus Box 7305, Chapel Hill, NC 27514; email: jared_weiss@med.unc.edu.
Bora Youn, PhD, can be reached at Brown University, 121 S. Main St., Box G-S121-3, Providence, RI 02912; email: younbora@gmail.com.
Disclosures: Weiss reports grants from Celgene for the current study; personal fees from AstraZeneca, EMD Serono and Regeneron; grants and honoraria from Celgene and Pfizer; and grants from Merck and Novartis for work performed outside of the current study. Youn reports no relevant financial disclosures. Please see the studies for all other authors’ relevant financial disclosures. Aggarwal and Langer report no relevant financial disclosures.
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Aggarwal C and Langer CJ. Cancer. 2020;doi:10.1002/cncr.32625.
Weiss JM, et al. Cancer. 2020;doi:10.1002/cncr.32573.
Youn B, et al. Cancer. 2020;doi:10.1002/cncr.32624.
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