What Role Will Avelumab Play in Lung Cancer?
The anti–programmed death ligand 1 (PD-L1) agent avelumab did not improve overall survival compared with docetaxel in a phase III trial of patients with PD-L1–positive non–small-cell lung cancer (NSCLC) who had already received platinum-based therapy.
“Antibodies targeting the immune checkpoint molecules PD-1 or PD-L1 improve overall survival compared with standard-of-care chemotherapy in patients with metastatic NSCLC,” wrote study authors led by Fabrice Barlesi, MD, of Aix Marseille University in France. More recent studies have expanded some of those agents’ approvals into earlier NSCLC settings.
The new study compared avelumab, an anti–PD-L1 agent, with docetaxel in patients with stage IIIB or IV NSCLC; all patients had progressed after platinum-based therapy. The results were published in Lancet Oncology.
The JAVELIN Lung 200 study included a total of 792 patients treated at 173 hospitals in 31 countries. They were randomized to receive either avelumab (396 patients, 264 PD-L1–positive tumors) or docetaxel (396 patients, 265 PD-L1–positive tumors); the primary analysis was only of the PD-L1–positive patients. Just over two-thirds of the study population was male, and a similar proportion was white. Approximately 90% of the study participants had received one prior line of therapy.
The median overall survival did not significantly differ between the groups, at 11.4 months with avelumab and 10.3 months with docetaxel, for a hazard ratio (HR) of 0.90 (96% CI, 0.72–1.12; P = .16).
PD-L1 positivity was defined as expression of PD-L1 in at least 1% of tumor cells; when this was adjusted to higher cutoffs, avelumab did have greater efficacy. In patients with at least 50% expression (168 patients in the avelumab group, 147 in the docetaxel group), the median OS was 13.6 months with avelumab and 9.2 months with docetaxel, for an HR of 0.67 (95% CI, 0.51–0.89; P = .0052). At at least 80% expression (120 and 106 patients, respectively), the median OS was 17.1 months and 9.3 months, respectively, for an HR of 0.59 (95% CI, 0.42–0.83).
Grade 3–5 adverse events occurred in 10% of avelumab patients and in 49% of docetaxel patients. With avelumab, the most common such adverse events included infusion-related reactions and increased lipase, while with docetaxel the most common included neutropenia, febrile neutropenia, and decreased neutrophil counts. Serious adverse events were more common with docetaxel, and there were 4 treatment-related deaths with avelumab compared with 14 with docetaxel.
“Overall, although this trial did not meet its primary endpoint, the clinical activity and safety noted in this study support further studies of avelumab in patients with NSCLC,” the authors wrote.
Sameep Sehgal, MD, of Temple University’s Lewis Katz School of Medicine in Philadelphia, who was not involved with the research, said the results “do give us pause,” and that clinicians should remember that not all immune therapeutic agents are the same. “The results may dampen the enthusiasm about using avelumab in advanced lung cancer,” he told Cancer Network, though he pointed out that other studies have shown improved survival with other immunotherapeutic agents. “Improved survival in patients with higher PD-1 expression is encouraging and avelumab may have a role in this subgroup of patients in the future.”
SAN ANTONIO -- Aggressive, targeted radiation therapy delayed cancer progression and showed a strong signal toward improving overall survival (OS) in patients with oligometastatic disease, the SABR-COMET study found.
At a median 27 months follow-up, progression-free survival (PFS) was 12 months in patients treated with standard palliative care plus stereotactic body radiation therapy (SBRT) compared with 6 months in those who received palliative care alone (P=0.001), reported David Palma, MD, PhD, of the London Health Sciences Centre in London, Ontario, Canada.
And at 5 years, 46% of patients in the SBRT arm were alive compared with 24% in the control arm. Median OS was numerically better in SBRT-treated patients, at 41 months (95% CI 26 months to not reached) compared with 28 months (95% CI 19 to 33 months) in the control group (P=0.09).
Most of the patients had oligometastatic (≤3 lesions) cancers of the prostate, breast, colon, and lung.
Results of the trial will be presented next week in a plenary session at the American Society for Radiation Oncology (ASTRO) meeting here.
"It's been a big source of controversy as to how to best manage these patients," Palma told MedPage Today. "For many years people have suggested that maybe we should use aggressive treatments like surgery or stereotactic radiation where others said that kind of approach would be futile."
Palma said that he hopes this study, which will continue to follow patients for up to 10 years, will help to reduce that level of controversy. The trial was designed to detect a signal of benefit (P<0.20) but the PFS benefit was found to be definitive.
"The results are very tantalizing in that we're getting 13 months of difference in the survival, and the percentage of patients alive at 5 years is roughly double," said Palma.
"At our center, it's changed how we are practicing," he said, but noted that without the significant improvement in OS, decisions will ultimately come down to the individual oncologist and his or her discussions with patients.
"Many people feel that a progression-free survival benefit is enough to change practice, but others will want more information," he added.
"This study has very exciting implications for patients with metastatic disease, in particular for those with only a couple sites of metastases," James B. Yu, of Yale Cancer Center and Smilow Cancer Hospital in New Haven, Connecticut, told MedPage Today in an email.
"I can envision a future where ever more sophisticated molecularly-targeted therapies and immunotherapies in combination with precisely targeted and non-invasive radiosurgery lead to the cure of previously incurable metastatic disease," said Yu, who was not involved in the study. "There will always be a role for locally directed therapy -- and as radiosurgery gets more precise (with improvements in patient tracking and tumor visualization) and easier to plan and deliver (with artificial intelligence-driven improvements in radiation treatment planning), treatment of multiple lesions will become commonplace."
The open-label SABR-COMET trial enrolled 99 patients from 2012 to 2016 with recurrent cancer and good performance status (ECOG 0-1) from Australia, Canada, Scotland, and the Netherlands. Among the 99 patients, there were 16 with prostate cancer, and 18 with breast, lung, and colorectal cancers each. Patients with up to five metastases were included in the trial, but 93% had between one and three. Some patients who developed additional lesions during the trial were successfully treated with additional ablation.
Palma said that patients with different cancer types were included because SBRT works fairly well regardless of histology and other trials have failed to fully accrue in this setting.
The two groups of patients -- median age 68 and 59% men -- had similar baseline characteristics and were randomized 2:1 to SABR plus standard palliative care or palliative care alone. Adverse events (AEs) grade ≥2 were more common with SBRT (30% vs 9%). Most comment events were fatigue, dyspnea, muscle, joint, bone, or other types of pain. Three deaths occurred in the investigational arm due to AEs.
No differences were seen with regard to quality of life. At 6 months post-treatment, overall scores on the Functional Assessment of Cancer Therapy General (FACT-G) questionnaire were high in both treatment arms: 82.5 with SBRT versus 82.6 (P=0.992). And no significant differences were seen on the questionnaire's functional, emotional, physical, and social subscales.
A follow-up phase III study, SABR-COMET-3, will test the approach in patients with up to three metastatic lesions, and the phase III SABR-COMET-10 will test this approach with lower SBRT doses in patients with up to 10 lesions.
The study was funded by the Ontario Institute for Cancer Research and a London Regional Cancer Program Catalyst grant.