Continuous nivolumab appears effective, safe in advanced NSCLC
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Continued nivolumab treatment after 1 year appeared effective and safe for certain patients with advanced non-small cell lung cancer, according to an exploratory analysis of the CheckMate 153 study published in Journal of Clinical Oncology.
“CheckMate 153 was built upon the early successes of the landmark studies CheckMate 052 and CheckMate 017,” David M. Waterhouse, MD, MPH, co-chair of the department of clinical research at Oncology Hematology Care in Cincinnati, told Healio. “Although immunotherapy was first initiated in the melanoma population, the world really did not hear about it or recognize the importance of this research until those landmark studies cemented the importance of immunotherapy [for] the treatment of NSCLC. They were also the first studies to give hope to this patient population and suggest a possibility of long-term survival, with the 5-year survival results soon to be published.”
Researchers launched the current trial to gain more insight into immune checkpoint inhibition and its effects on patients in the community setting, where nearly 85% of all cancer care takes place, according to Waterhouse.
“As this trial was launched at the heels of CheckMate 052 and 017, it was soon appreciated that there was a unique opportunity to randomly assign patients, after 1 year of therapy, to continuation vs. stopping their treatment with plans to resume upon progression. No one had any idea whether continued treatment would benefit our patients,” he said.
The phase 3b/phase 4 CheckMate 153 study included 1,428 patients with previously treated advanced NSCLC. Patients received monotherapy with the anti-PD-1 antibody nivolumab (Opdivo, Bristol Myers Squibb) via IV at a dose of 3 mg/kg once every 2 weeks.
Researchers randomly assigned 252 patients still on treatment at 1 year (intention-to-treat population) to either continue nivolumab until disease progression or unacceptable toxicity (n = 127) or to stop treatment with the option of on-study retreatment after disease progression (n = 125).
The PFS population included 89 patients in the continuous arm and 85 patients in the 1-year fixed-duration arm who did not progress on treatment and had not initiated other systemic anticancer therapy before randomization.
Minimum follow-up after random assignment was 13.5 months.
Results showed median PFS of 24.7 months in the continuous treatment group vs. 9.4 months in the 1-year fixed-duration group in the PFS population (HR = 0.56; 95% CI, 0.37-0.84).
In addition, median OS from random assignment improved with continuous vs. 1-year fixed-duration treatment in both the PFS (not reached vs. 32.5 months; HR = 0.61; 95% CI, 0.37-0.99) and intent-to-treat populations (not reached vs. 28.8 months; HR = 0.62; 95% CI, 0.42-0.92).
Researchers observed few new-onset treatment-related adverse events and no new safety signals.
“Patients receiving an immune checkpoint inhibitor in the second-line setting for NSCLC should consider continuing treatment until disease progression or unacceptable toxicity,” Waterhouse said. “However, we are now treating the majority of patients with an immune checkpoint inhibitor in the first line, either as a single agent, part of a dual immunotherapy combination or alongside systemic chemotherapy. ... Many first-line trials arbitrarily discontinued treatment after a set period of time, and we do not know whether it is important to continue the immune checkpoint inhibitor indefinitely.”
Waterhouse said there is a great need for further innovation and breakthrough therapies.
“[Although] many patients benefit from immune checkpoint treatment in the first-line setting, a majority eventually fail and die of this harsh and all-too-common disease,” he added. “This underscores the need for ongoing support of clinical research, as we are far from where we want to be. There are many pharmaceutical companies competing in this clinical space, and my fear is that there are too many ‘me too’ trials as opposed to novel treatments aiming for breakthrough. That said, we are making significant progress.
“It seems like it was not long ago that there was a debate raging whether it was appropriate to even treat patients with advanced NSCLC,” Waterhouse added. “Clinicians and patients alike were nihilistic and lacked hope. We have given them back hope, and we need to give them even more hope.”
Despite the study’s inherent limitations, including a sample size for randomization based on a convenience sample, the results of CheckMate 153 allow researchers to design more rational research into optimal duration of immunotherapy, Marina Chiara Garassino, MD, researcher in the thoracic oncology unit of the department of medical oncology at Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori in Milan, and colleagues wrote in an accompanying editorial.
“For the time being, in the absence of clear data, the integration of patients’ preferences could help, especially in decisions in which uncertainty is highly likely in this case. From this perspective, a shared decision-making paradigm will allow both patients and clinicians to recognize and pursue the option that best fits the individual,” they wrote.
References:
Garassino MC, et al. J Clin Oncol. 2020;doi:10.1200/JCO.20.02191.
Waterhouse DM, et al. J Clin Oncol. 2020;doi:10.1200/JCO.20.00131.
For more information:
David M. Waterhouse, MD, MPH, can be reached at Oncology Hematology Care, 4350 Malsbary Road, Floor 1, Cincinnati, OH 45242; email: david.waterhouse@usoncology.com.
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