ASCO Recommends Trilaciclib in Extensive-Stage Small Cell Lung Cancer in Guideline Update

Raj Malik, MD, chief medical officer of G1 Therapeutics

In their updated guidelines for patients with small cell lung cancer (SCLC), ASCO has recommended the CDK4/6 inhibitor trilaciclib (Cosela) as a myeloid supportive agent for patients with untreated or previously treated extensive-stage SCLC who are receiving chemotherapy or chemoimmunotherapy.^1,2

In the new guidelines, which were published on October 11, 2023, recommendation 8.1 reads, “Trilaciclib or granulocyte colony–stimulating factor may be offered as a myeloid supportive agent for patients with untreated or previously treated extensive-stage SCLC who are undergoing treatment with chemotherapy or chemoimmunotherapy.” ASCO noted that this recommendation was evidence based and that the benefits of the intervention outweigh the harms. They characterized their evidence quality as moderate and the strength of the recommendation as weak.²

“The inclusion of trilaciclib in these new ASCO SCLC guidelines is essential, as they inform treatment decisions by US physicians caring for people living with SCLC,” Raj Malik, MD, chief medical officer of G1 Therapeutics, the manufacturer of trilaciclib, said in a news release. “The mounting body of evidence from our clinical trials and real-world studies demonstrates the potential of trilaciclib to protect the bone marrow of patients with extensive-stage SCLC against the harmful effects of chemotherapy. These updated guidelines provide further clarity and confidence to physicians considering cytotoxic therapies for their patients with untreated and previously treated SCLC.”¹

Previously, trilaciclib was granted approval by the FDA to reduce the frequency of chemotherapy-induced bone marrow suppression in adults with extensive-stage SCLC receiving certain types of chemotherapy. The agent gained the indication in February 2021; it was the first therapy in its class to be approved.³

The updated ASCO recommendation was based on findings from a review of the available literature.²

Findings from a phase 1b/2 trial (NCT02499770) showed that patients with SCLC being treated with frontline chemotherapy who received trilaciclib experienced numerical improvements in objective response rate (ORR; P = .3831), progression-free survival (PFS; P = .1695), and overall survival (OS; P = .6107). Additionally, trilaciclib significantly reduced the duration of severe neutropenia and lessened the number patients who required red blood cell transfusions as well as reduced transfusion rates.⁴

Additionally, data from a phase 2 trial (NCT03041311) demonstrated that patients with newly diagnosed extensive‐stage SCLC who were treated with trilaciclib before first-line carboplatin, etoposide, and atezolizumab (n = 52; Tecentriq) experienced statistically significant decreases in the mean duration of severe neutropenia in cycle 1 (0 vs 4 days; P < .0001) compared with placebo (n = 53). Trilaciclib also significantly reduced the occurrence of severe neutropenia compared with placebo, at 1.9% vs 49.1%, respectively (P < .0001). Patients experienced grade 3/4 adverse effects at a rate of 55.7% vs 77.4%, respectively.⁵

Finally, in another phase 2 trial (NCT02514447), patients with previously treated extensive-stage SCLC who received trilaciclib prior to topotecan (n = 32) experienced a mean duration of severe neutropenia of 2 days (standard deviation [SD], 3.9) compared with 7 days (SD, 6.2) among patients who received placebo prior to topotecan (n = 29; adjusted one-sided P < .0001). Moreover, the rate of severe neutropenia was 40.6% vs 75.9%, respectively (P = .016).⁶

The updated ASCO SCLC guidelines were developed by a panel of medical oncology, thoracic surgery, radiation oncology, pulmonary, community oncology, research methodology, and advocacy experts. The literature review examined systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2022. Members of the panel used available evidence and informal consensus to inform the guideline reccomendations.²

References

1. G1 Therapeutics’ COSELA (trilaciclib) recommended in updated small cell lung cancer guidelines from the American Society of Clinical Oncology (ASCO). News release. G1 Therapeutics. October 18, 2023. Accessed October 27, 2023. https://finance.yahoo.com/news/g1-therapeutics-cosela-trilaciclib-recommended-120000935.html
2. Khurshid H, Ismaila N, Bian J, et al. Systemic therapy for small-cell lung cancer: ASCO-Ontario Health (Cancer Care Ontario) Guideline. J Clin Oncol. Published online October 11, 2023. doi:10.1200/JCO.23.01435
3. FDA approves drug to reduce bone marrow suppression caused by chemotherapy. News release. FDA. February 12, 2021. Accessed October 27, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-drug-reduce-bone-marrow-suppression-caused-chemotherapy
4. Weiss JM, Csoszi T, Maglakelidze M, et al. Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019;30(10):1613-1621. doi:10.1093/annonc/mdz278
5. Daniel D, Kuchava V, Bondarenko I, et al. Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: a multicentre, randomised, double-blind, placebo-controlled phase II trial. Int J Cancer. 2020;148(10):2557-2570. doi:10.1002/ijc.33453
6. Hart LL, Ferrarotto R, Andric ZG, et al. Myelopreservation with trilaciclib in patients receiving topotecan for small cell lung cancer: results from a randomized, double-blind, placebo-controlled phase II study. Adv Ther. 2021;38(1):350-365. doi:10.1007/s12325-020-01538-0