In new small cell lung cancer guidelines, the European Society of Medical Oncology calls for upfront atezolizumab or durvalumab in combination with four to six cycles of etoposide and a platinum for stage 4 disease.
The strong recommendation is based on two phase 3 trials that showed improved overall survival when the checkpoint inhibitors were added to standard chemotherapy. “With very similar results, and in the context of a severe unmet need, both trials justify the need for immunotherapy in the frontline setting” and established “new standards of care” for stage 4 disease, the group said. “Atezolizumab or durvalumab in combination with a platinum plus etoposide should be offered to all eligible chemotherapy-naive patients” with a performance status of 0-1, said the group led by Anne-Marie Dingemans, MD, PhD, a pulmonology professor at Maastricht (the Netherlands) University Medical Center.
Alessio Cortellini, MD, a consulting oncologist and visiting researcher at Imperial College London, said he strongly endorses the recommendation when asked for comment.
“The addition of a PD-L1 inhibitor to a platinum/etoposide backbone is the first strategy that has led to a significant benefit in terms of overall survival. After decades of disappointing results, the bar has” been raised, said Dr. Cortellini.
New inhibitor
EMSO also incorporated the new RNA polymerase II inhibitor lurbinectedin into their guidelines as an option for patients progressing on or after first-line platinum-based chemotherapy.
The agent was approved by the U.S. Food and Drug Administration in June 2020 for metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.
The recommendations – more than 50 in all – are based on a literature review and expert opinion, and cover SCLC diagnosis, staging, treatment, and follow-up, with flowcharts outlining treatment pathways.
Atezolizumab earned the endorsement following the IMpower133 trial, which showed a median overall survival of 12.3 months for atezolizumab in combination with carboplatin and etoposide, versus 10.3 months on chemotherapy alone; 34% of the atezolizumab group was alive at 18 months versus 21% in the placebo arm.
The durvalumab recommendation is based on the CASPIAN trial, in which the addition of durvalumab to platinum plus etoposide improved median overall survival from 10.5 to 12.9 months; 32% of durvalumab patients were alive at 18 months versus 24.8% in the chemotherapy-alone arm.
ESMO said “it is important to stress that, in both trials,” patients were in good clinical condition with a median age in the early 60s, so relatively young for SCLC. Also, the modest benefits “clearly emphasize the need for” biomarkers that predict response in order to better select patients.
Immunotherapy has improved cancer treatment across many malignancies and continues to be actively investigated in SCLC, but so far only atezolizumab and durvalumab have phase 3 evidence of benefit.
Makers of the blockbuster checkpoint inhibitors nivolumab and pembrolizumab recently withdrew their FDA approval for stage 4 SCLC that’s progressed after platinum-based chemotherapy and at least one other line of therapy; phase 3 trials failed to confirm the modest survival benefit found in early studies.
Lurbinectedin earned its place in the guidelines based on a single-arm study with 105 relapsed patients that showed an overall response rate of 22.2% in platinum-resistant and 45% in platinum-sensitive patients, with a median overall survival of 9.3 months.
The jury is still out, however. A phase 3 trial of lurbinectedin plus doxorubicin versus topotecan or CAV [cyclophosphamide, adriamycin, and vincristine] for advanced recurrent disease failed to meet its endpoint of superior overall survival, according to a recent press release from the its maker.
“It might be a bit early to discuss” routine use of lurbinectedin, although having it available is good “since literally nothing works in the second line setting,” Dr. Cortellini said.
There was no external funding for the work. The authors had numerous ties to pharmaceutical companies, including Dr. Dingemans who reported adviser and speakers fees and/or research funding from Roche, Lilly, Bristol-Myers Squib, and others. Dr. Costellini reported speakers fees from Novartis, Astrazeneca, and Astellas and consultant payments from Bristol-Myers Squibb, Roche, MSD, and AstraZeneca.