Biomarker Testing Provides a Way Forward for Increasingly Accurate Lung Cancer Diagnosis and Management

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Partner | Cancer Centers | <b>University of Chicago Medicine Comprehensive Cancer Center</b>

Giuseppe Lo Russo, MD, PhD, highlights the future role of liquid biopsy, the evolution of targeted therapies for KRAS G12C mutations, data to look forward to with EGFR-targeted agents, and the striking effects the COVID-19 pandemic has had on the mortality rates of patients with lung cancer.

Comprehensive biomarker testing establishes a strong foundation for improved, individualized lung cancer care, according to Giuseppe Lo Russo, MD, PhD, who emphasized that this testing should become the standard practice across the field to best direct the use of effective targeted therapies.

“In recent years, biomarker testing has completely revolutionized the management of advanced non–small cell lung cancer [NSCLC],” Lo Russo said in an interview with OncLive® following an Institutional Perspectives in Cancer (IPC) webinar on lung cancer, which he cochaired with Marina Chiara Garassino, MD. “Deep biomolecular characterization must become the standard for all patients diagnosed with lung cancer, [starting from] diagnosis and carried [throughout] the early stages [of disease].”

In the interview, Lo Russo, a medical oncologist in the Department of Oncology at the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, summarized the focuses of each presentation from the meeting. He highlighted the future role of liquid biopsy, the evolution of targeted therapies for KRAS G12C mutations, data to look forward to with EGFR-targeted agents such as amivantamab-vmjw (Rybrevant) and mobocertinib (Exkivity), and some of the most striking effects the COVID-19 pandemic has had on the mortality rates of patients with lung cancer.

OncLive®: Raffaele Califano, MD, of The Christie and Manchester University Hospital in Manchester, United Kingdom, presented on biomarker testing in lung cancer. How can biomarker testing and appropriate testing technologies contribute to better and more individualized patient care?

Lo Russo: Currently, most first-line treatment regimens cannot be started without an appropriate biomolecular characterization of the disease. In the future, the role of biomolecular testing will increase, both in the frontline and during [subsequent lines of] therapy.

Liquid biopsy may become increasingly important to monitor resistance mechanisms in the event of disease progression and to evaluate minimal residual disease after surgery or responses to systemic therapies. Tissue biomolecular characterization and liquid biopsy will be useful in the future, and they may be complementary.

Javier Baena, MD, of the Hospital Universitario 12 de Octubre in Madrid, Spain, talked about targeted therapies for NSCLC. Where are KRAS G12C inhibitors most effective in KRAS G12C–mutant NSCLC?

KRAS G12C inhibitors seem to be the best treatment choice for patients with this mutation who are resistant to chemotherapy and immunotherapy. We do not yet have data to say whether KRAS inhibitors will replace immunotherapy and chemoimmunotherapy in the first line or if the combination of KRAS inhibitors and chemoimmunotherapy will become the new gold standard.

Regarding the efficacy of immunotherapy in patients with KRAS mutations, there are enough data to indicate that in this moment, immunotherapy plus chemotherapy or as a monotherapy should be considered the gold standard in these patients. However, in the future, the paradigm may change with new data from ongoing studies.

Dr Baena also talked about RET fusions. What did the phase 1/2 LIBRETTO-001 study (NCT03157128) show about overall response rates in patients with RET fusion–positive tumors who were treated with selpercatinib (Retevmo), and how does the future look for RET inhibitors in this population?

The data from LIBRETTO-001, which were positive in terms of efficacy and tolerability, can lead us to affirm that treatment with RET inhibitors must always be taken into consideration in patients with RET fusions. It will likely become a standard monotherapy even into the first line. We’re still waiting for data from comparative phase 3 studies with first-line chemotherapy or chemoimmunotherapy.

What is the potential role of amivantamab and mobocertinib in patients with EGFR mutations, as discussed in the presentation on exon 20 and other EGFR-targeted agents, given by Giannis Mountzios, MD, MSc, PhD, of the Henry Dunant Hospital Center in Athens, Greece?

In this setting, we have interesting efficacy and tolerability data coming from different studies, especially [with the agents] amivantamab and mobocertinib, more so than with poziotinib. We must still wait to understand in which phase of the patient’s therapeutic path these drugs will be placed, such as in the first line, the second line, or later.

We also need to wait to understand whether they can be used sequentially and whether they can be used with chemotherapy or with chemoimmunotherapy. We do not have these data now, but [we may in the future].

Dr Garassino, of the University of Chicago Comprehensive Cancer Center in Chicago, Illinois, presented about COVID-19 and lung cancer with a focus on the TERAVOLT experience. What are some of the effects of COVID-19 on patients with lung cancer that can increase their mortality rates?

There are many direct and indirect detrimental effects of COVID-19 on patients with lung cancer. One of the most relevant is the low rate of patients diagnosed with lung cancer and COVID-19 who receive the maximum treatment for [the virus], such as intubation. In many cases, lung cancer diagnosis alone, regardless of prognosis, excludes these patients from COVID-19 treatment. This has been a major problem for these patients in the past few years, especially in Italy.

What have been some of the most prevalent effects of the pandemic on health care workers, specifically those working in the lung cancer field?

[There have been numerous effects], especially the frustration of seeing so many patients dying every day; we lost a lot of patients. Also, in the past, when patients arrived in the hospital, and the doctors knew they had lung cancer, these patients didn’t receive the best treatment for COVID-19. The situation is better now.

What ongoing lung cancer research is happening at the Fondazione IRCCS Istituto Nazionale dei Tumori?

We have many trials that are being done in different settings. One of the most interesting trials is [the phase 3 AcceleRET-Lung trial (NCT04222972), which is investigating] pralsetinib [Gavreto] vs chemotherapy in the first-line [treatment of patients with RET fusion–positive, advanced NSCLC. This trial is similar to the phase 3 LIBRETTO-431 trial (NCT04194944), which we conducted] in the past, and investigated selpercatinib in the first-line population.

We also have several ongoing trials that are being conducted in patients who have progressed after chemoimmunotherapy. We have 2 families of trials: 1 with antibody-drug conjugates such as those directed toward TROP2. [The other family of trials is investigating] different immunotherapies like TIGIT inhibitors and CD96 inhibitors.