In patients with extensive-stage small cell lung cancer (SCLC), adding trilaciclib to standard-of-care chemotherapy demonstrated meaningful delays in deterioration of myelosuppression-related symptoms, according to Jared Weiss, MD, of the UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, and colleagues. Based on these findings, the investigators maintain that trilaciclib may make myelosuppressive chemotherapy safer.

Jared Weiss, MD

Previously, three phase II randomized, double-blind, placebo-controlled SCLC trials focused on patients with extensive-stage SCLC who were treated with the cyclin-dependent kinase (CDK) 4/6 inhibitor trilaciclib prior to cytotoxic chemotherapy. In all three trials, trilaciclib demonstrated multilineage myelopreservation, evidenced by decreases in the duration and occurrence of severe neutropenia and the occurrence of red blood cell transfusions.

At the 2019 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Annual Meeting in San Francisco, coauthor Shannon Morris, MD, PhD, Vice-President of G1 Therapeutics, manufacturer of trilaciclib, Research Triangle, North Carolina, presented the effects of trilaciclib on symptoms and functional impairment, based on patient-reported outcomes from these trials.¹

Addressing Myelosuppression in Patients Receiving Chemotherapy

Myelosuppression remains a significant challenge in this patient population. Despite the availability of interventions such as granulocyte-colony stimulating factor and erythropoietin transfusions, many patients still experience high-grade toxicities such as neutropenia, anemia, and thrombocytopenia. Further, interventions for these toxicities are typically administered after an adverse

These data show that we can make myelosuppressive chemotherapy better. ... We can also improve the patient’s experience on chemotherapy.

— Shannon Morris, MD, PhD

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event and are associated with their own side effects.

According to Dr. Morris, trilaciclib has the potential to prevent multilineage myelosuppression while reducing the need for these interventions and their associated side effects. “Because trilaciclib acts early in hematopoiesis, patients may see benefits across all lineages with one drug,” she explained. “So, you can have protection of white blood cells, red blood cells, platelets, and lymphocytes.”

Design of G1T28 Trials

In all three trials, patients with SCLC received standard-of-care chemotherapy with trilaciclib or placebo. Patients in the G1T28-03 trial were previously treated and received topotecan, patients in the G1T28-05 trial were newly diagnosed and received etoposide/carboplatin in combination with atezolizumab, and patients in the G1T28-02 trial were newly diagnosed and received etoposide/carboplatin.

Patient-reported outcome symptom and functioning data were measured through the use of validated questionnaires, collected on days 1 and 10 of each cycle (day 1 for G1T28-05). The Functional Assessment of Cancer Therapy (FACT)–Anemia measured fatigue and other aspects of patients’ anemia experience (ie, dyspnea, dizziness), and the FACT–Lung was used to measure generic- and lung cancer–related aspects of quality of life.

“Patients get worried about their counts because their doctors get worried about their counts,” Dr. Morris noted. “But what they’re really interested in is their symptoms and how they’re feeling.”

The investigators conducted three exploratory analyses on patient-reported outcomes: change from baseline instrument scores, proportion of patients with symptom improvement and/or deterioration (defined as a change from baseline exceeding clinically meaningful thresholds), and time to deterioration (defined as time to first deterioration, confirmed at the next visit).

Patient-reported outcome completion rates were high across all studies (> 80%) for the first 4 to 6 cycles (the time period for which analyses were performed), and enrolled patients had a moderate level of functioning. “Since they were in the middle, we could see improvement or deterioration,” noted Dr. Morris. “That enabled us to see the patients swing on either side of their baseline levels.”

Improvement in Fatigue

“When we were looking at data during the exploratory phase, it became quite clear to us that fatigue is the most common symptom experienced by these patients,” Dr. Morris reported. “And, it turns out, trilaciclib has a significant effect on that symptom.”

Data from a pooled analysis of all three studies showed that patients who received trilaciclib had improved symptoms of fatigue during the first four cycles of treatment, with more pronounced effects for those being treated in the second or third line. Meanwhile, symptoms of fatigue deteriorated in patients who received placebo.

Trilaciclib also delayed the deterioration of a variety of patient functioning and symptom measures over time compared with placebo, with a median delay to deterioration for fatigue of 4.7 months, delay for anemia of 3.5 months, and delay for functional well-being of 4 months. “In a patient with SCLC whose median overall survival is abysmal, that is significant time,” noted Dr. Morris.

“These data show that we can make myelosuppressive chemotherapy better across multiple lineages with one drug,” Dr. Morris added. “We can also improve the patient experience on chemotherapy, and that’s very important to our patients.” ■

DISCLOSURE: Dr. Morris is Vice-President of G1 Therapeutics, the manufacturer of trilaciclib. Dr. Weiss has served in a consulting or advisory role with G1 Therapeutics and Genentech and has received research funding from G1 Therapeutics.

REFERENCE

1. Weiss J, Skaltsa K, Gwaltney C, et al: Results from three phase 2 randomized, double-blind, placebo-controlled small cell lung cancer trials. 2019 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology International Symposium on Supportive Care in Cancer. Abstract eP723. Presented June 21, 2019.