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Improving Survival and Managing Costs in NSCLC Using Clinical Care Pathways
In a session at the 6th annual Oncology Clinical Pathways Congress, Mark Socinski, MD, Executive Director, Thoracic Cancer, Advent Medical Group, discussed the current and ever-evolving treatment landscape of non-small cell lung cancer (NSCLC) and the development and implementation of optimal clinical pathways in this complex disease.
The identification of an expanding list of oncogenic drivers and the development of targeted drugs and immunotherapies have revolutionized the treatment of NSCLC. Recent innovations in biomarker-driven and immunotherapeutic therapies continue to rapidly expand treatment options and advance the management of NSCLC, but variations in care and significant economic burden associated with the disease continue to hamper optimal outcomes.
Clinical pathways focused on NSCLC must be continually assessed and refined to help stakeholders synthesize multiple factors, including molecular testing strategies and newer and emerging therapies, to ensure delivery of the most clinically appropriate and cost-effective treatment tailored to the most appropriate patients.
This session described the role of genetic mutations and patient-specific biomarkers in NSCLC and the importance of molecular testing, explained how to apply information on newer and emerging therapies to optimize clinical pathways for NSCLC, and evaluated current guidelines for NSCLC, including considerations for therapy selection and subsequent sequencing.
Clinical guidelines recommend biomarker testing at diagnosis. Recent data from the 2021 ASCO Annual Meeting had shown that the rate of NGS testing was less than 50%, though it had increased from 33% in September 2018 to 45% in March 2020.
Best practices for overcoming biomarker testing challenges include integrating liquid biopsy, integrating tissue, and supporting effective multidisciplinary collaboration so that all members of the team know the importance of biomarker testing in NSCLC.
Dr Socinski structured his presentation as though it were a pathway, beginning with the question, “does the patient have a driver?” He notes, “If they do have a driver, they should get targeted therapy.”
In NSCLC, there are currently 8 oncogenic drivers that have specific FDA-approved therapies associated with them: EGFR, ALK, KRAS (G12C), ROS1, BRAF, NTRK, RET, and MET exon 14.
Highlighting the importance of testing, Dr Socinski discussed data from the ALEX trial. In the ALEX trial, comparing alectinib vs crizotinib in ALK-positive advanced NSCLC, the median overall survival at 5 years has not yet been reached. “It’s all about getting the right treatment to the right patient at the right time,” says Dr Socinski, adding, “that’s why you need to test for these abnormalities and get patients treated appropriately.”
If the patient does not have a driver, the next question Dr Socinski addressed was, “is the patient a candidate for immunotherapy?” If the patient does not have a driver, and is not a good candidate for immunotherapy, they should receive standard chemotherapy. In patients who are good candidates for immunotherapy, the next question is, “is the patient a candidate for immuno-monotherapy?”
Dr Socinski recommends that patients with low-volume disease, are relatively asymptomatic, and have very high PD-L1 expression as good candidates for immune-monotherapy, whereas patients with high-volume disease, heavy symptom burden, lesser PD-L1 expression, and PD-L1 <50% may not be good candidates for this treatment. Dr Socinski recommends that these patients be treated using chemoimmunotherapy.
If a patient is not a candidate for immuno-monotherapy, the next question Dr Socinski asks is, “is the patient a candidate for bevacizumab?” For those who are candidates for bevacizumab, Dr socinski highlights findigns from the IMpower150 trial, a phase III global trial that stratified for liver metastases at randomization. The addition of bevacizumab to chemotherapy in patients with non-squamous NSCLC resulted in increased overall survival and progression-free survival, compared to standard chemotherapy alone. There were particularly high response rates in patients with a high PD-L1 expression.
In patients with liver metastases or those who had EGFR-mutation positive NSCLC, the addition of bevacizumab and atezolizumab to chemotherapy showed a great advantage over atezolizumab plus chemotherapy and bevacizumab plus chemotherapy.
For patients who are not candidates for bevacizumab, Dr Socinski pointed to trials KEYNOTE-189 and IMpower130 for the standard of care. KEYNOTE-189, a study that grafted the pembrolizumab onto the platform of pemetrexed and carboplatin (the most commonly used platinum doublet in the US), adding immunotherapy and maintenance therapy, suggested that long-term survival (3 or more years) was greater in pembrolizumab plus chemotherapy, as it more than doubled the median survival across all PD-L1 positive tumor proportion scores.
The IMpower130 study compared combination atezolizumab carboplatin nab paclitaxel vs combination carboplatin nab paclitaxel in non-squamous NSCLC, showing positive results in OS and progression-free survival for combination atezolizumab carboplatin nab paclitaxel.
The KEYNOTE-407 study expanded on the IMpower130 study, examining patients with squamous NSCLC, and adding pembrolizumab, concluding that the addition of chemotherapy to immunotherapy improves the overall survival rate in this population.
The Checkmate 227 study helped identify where these IO-IO combinations are suitable, specifically combination of nivolumab and ipilimumab, however, it compared combination nivolumab ipilimumab with chemotherapy alone, yet chemotherapy alone is no longer used. Dr Socinski states “the question would be: ‘how would nivo ipi compare to chemo plus a single immunotherapy agent?”
The KEYNOTE-598 study included patients with stage IV NSCLC who had a PD-L1 tumor proportion score of 50% or greater, and compared pembrolizumab alone vs pembolizumab plus ipilimumab, finding no difference in OS between the two regimens.
The CheckMate 9LA study compared chemo alone, as the control, vs combination nivolumab ipilimumab in patients with NSCLC. This is another example of an outdated study design, as the standard of care is, again, no longer chemo alone. Results were positive for combination nivolumab ipilimumab due to this study flaw.
Over the past 5 years, there have been some FDA approvals for immunotherapy in various platforms for stage IV NSCLC, improving the landscape for patients, as patients are doing significantly better with these approvals.
Pathways can help facilitate Dr Socinski’s initial goal of this presentation, which is to “get the right treatment to the right patient at the right time,” especially for general oncologists who take care of a number of different diseases, as opposed to specifically specializing in one type of cancer. “I think it would be almost impossible [for general oncologists] to keep up with the latest and greatest in every single tumor cycle, and that’s where pathways can be very helpful,” said Dr Socinski.
Pathways could help reduce cancer side effects from toxicities, through prescribing a regimen with limited toxicity that still maintains efficacy. Pathways can also help guide patients to the treatment with the least amount of costs, when efficacy and toxicity are equivalent.
Pathways improve quality and reduce costs for patients with NSCLC. A study from the Dana Farber Cancer Institute showed that implementing pathways reduced cost of care in NSCLC by 22% with no change in OS in advanced NSCLC. A study from UPMC and Indiana University demonstrated a reduction in the use of costly drugs in 82% of patients with metastatic colon cancer, saving over $700,000 in estimated annualized costs.
“Targeted therapies and incorporation of IO [immuno-monotherapy] strategies have changed OS outcomes for the better,” concluded Dr Socinski, adding, “Clinical pathways are critical tools to assure each patient gets the right treatment at the right time at the right cost.”
Socinski, M. Improving Survival and Managing Costs in NSCLC: The Role of Clinical Care Pathways. Presented at: The 2021 Oncology Clinical Pathways Congress; October 1-3, 2021; virtual.
