That the lung cancer community continues the journey toward a world where no one dies of lung cancer, even despite pandemic-related hurdles, was clear at the 2021 American Society of Clinical Oncology (ASCO) virtual conference held June 4-8.
Thousands of attendees from the U.S. and around the world, including oncologists, scientists, biotech and pharmaceutical representatives, advocates, and patients, discussed life-saving cancer research. The theme for this year’s conference, “Equity: Every Patient. Every Day. Everywhere,” was in recognition of the deep health disparities in our communities as well as a call to action to bring health equity to all cancer patients.
Researchers presented data on many different aspects of lung cancer treatment. Here we highlight some of the most impactful and interesting studies presented at this year’s meeting.
Results from the IMpower010 study demonstrated that the immunotherapy drug atezolizumab, given after adjuvant chemotherapy (chemotherapy given after surgery to stop the cancer from coming back) decreases the chances of the cancer recurring, when compared with chemotherapy alone. Atezolizumab seemed to work better in patients whose tumors expressed the PD-L1 protein.
Updated results from the Checkmate-816 study showed that the neoadjuvant nivolumab + chemotherapy (treatment given before surgery to decrease the size of the tumor) led to a significant reduction in tumor size, when compared with only chemotherapy. Patients treated with this combination were able to undergo surgery in which the entire cancer was able to be removed.
Video-assisted thoracoscopic surgery (VATS) is an increasingly popular way to access the lungs during a lung cancer surgery because it is less invasive than an open lung surgery. The VIOLET study demonstrated that VATS lobectomy for lung cancer is associated with less pain, fewer in-hospital complications, and a shorter hospital stay. Patients had better quality of life and shorter recovery periods after VATS, and had similar outcomes to open lung surgery. The VIOLET study strongly argues that VATS should be standard of care for lobectomy.
The STARS study, comparing stereotactic ablative radiotherapy (SABR) to VATS, showed that use of SABR for patients with Stage I NSCLC is a great treatment option instead of surgery. The outcomes of SABR are as good if not superior to VATS for this patient population and may therefore be a great option, especially for those patients who may not be eligible for surgery because of health conditions.
Updates on immunotherapy for NSCLC
Several studies reported continued success in using immunotherapy to treat NSCLC.
Checkmate 9LA trial, a phase 3 study comparing four cycles of chemotherapy to two cycles of a combination treatment of chemotherapy and two immunotherapies (nivolumab and ipilimumab), demonstrated the continued success of the immunotherapy plus chemotherapy regimen in advanced-stage NSCLC in the two-year update.
Checkmate 227’s four-year follow-up data demonstrated a continued, long-term overall survival benefit for the first-line treatment of advanced-stage NSCLC with nivolumab and ipilimumab), when compared with chemotherapy alone.
- PACIFIC’s five-year update showed continued long-term benefits for patients with unresectable stage III NSCLC when treated after concurrent chemoradiotherapy with durvalumab, compared with treatment with a placebo. Researchers estimate 43% of patients randomized to durvalumab remain alive after five years and approximately one-third of those patients have no evidence of disease progression.
While durvalumab continues to be the standard of care for stage III unresectable NSCLC patients, two clinical trials, KEYNOTE-799 (concurrent chemoradiotherapy + pembrolizumab) and AFT-16 (atezolizumab prior to and following chemoradiotherapy), reported promising results that could result in additional options for patients in the future.
Update on targeted therapies for NSCLC
Many interesting updates were reported in targeted therapies for NSCLC at the 2021 ASCO conference.
An exciting new treatment for KRAS G12C-mutant NSCLC, sotorasib, was recently approved by the FDA. Data from the CodebreaK 100 trial demonstrated the efficacy and safety of sotorasib.
Researchers are making headway in developing targeted therapies for EGFR exon20 insertion (EGFRex20ins) mutations. Poziotinib, a drug granted fast-track designation by the FDA earlier this year for the treatment of NSCLC with insertion mutations in HER2, demonstrated durable benefit with patients across all types of EGFRex20ins mutations whose cancers had progressed on chemotherapy. An oral tyrosine kinase inhibitor, mobocertinib, also targets EGFRex20ins and continues to show promising outcomes for patients. In addition, a phase 1 clinical trial of DZD9008, another EGFRexon20ins inhibitor, showed acceptable safety outcomes and promising anti-tumor results in a phase 1 trial.
We also saw new treatment options for EGFR+ NSCLC that have become resistant to osimertinib. These tumors may have an effective treatment option in the works–the combination of amivantamab and lazertinib. Another promising treatment option for patients who are resistant to EGFR-TKI treatment, could be patritumab deruxtecan, an antibody conjugate drug that demonstrated good efficacy in a phase 1 clinical trial. Researchers also presented the results of a phase 3 clinical trial demonstrating the efficacy of aumolertinib, a third-generation TKI already used in China to treat EGFR+ NSCLC patients. The researchers found aumolertinib outperformed gefitinib while maintaining adequate safety standards, suggesting it may be a promising third-generation EGFR-TKI option.
Researchers are also leveraging common breast cancer treatments to target HER2 mutations in pretreated advanced-stage NSCLC. One study demonstrated that treatment with two antibody drugs against HER2 (trastuzumab and pertuzumab) and docetaxel is feasible in these patients and could be an effective treatment approach for lung cancer patients.
Researchers are also working to target MET alterations in NSCLC. Researchers from the GEOMETRY mono-1 clinical trial presented updated results with current data to show that capmatinib continues to be a strong treatment option for METex14 skipping NSCLC patients. Researchers are also looking for treatment options for NSCLC patients with MET amplification mutations. The phase 2 VISION trial data showed that tepotinib, a highly selective MET inhibitor, is a promising option for the first-line treatment of patients with advanced NSCLC and MET amplification mutations.
A new RET-blocking drug, BOS172738, is being tested in a phase 1 clinical trial for patients with RET-altered NSCLC. The researchers reported the safety profile for the drug is strong and there is anti-tumor efficacy. Additional studies of BOS172738 in RET-altered NSCLC are underway.
Drugs that block new targets:
Many oncogenic genes in NSCLC, such as EGFR, MET and HER2, activate signaling cascades involving the protein SHP2. Scientists have been working to block SHP2 in NSCLC as an alternative treatment approach to conventional TKIs. TNO155, a novel SHP2-blocker, was tested in a phase 1 study. The results showed that TNO155 is effective at inhibiting SHP2 activity and it was well tolerated by patients. Several additional studies are underway to determine the optimal ways to utilize TNO155 treatment for patients.
NSCLC mutations called NRG1 fusions may be oncogenic, which can lead to overactivation of certain molecular pathways and cause tumorigenesis. Researchers have developed a treatment called zenocutuzumab, which blocks these NRG1 fusion proteins from activating downstream pathways. The phase 1 study presented at this year’s ASCO conference demonstrated the drug’s well-tolerated safety profile and efficacy in patients. While further studies are required, zenocutuzumab is a promising targeted therapeutic for advanced-stage NSCLC patients with NRG1-fusions.
Update on small cell lung cancer (SCLC):
Very exciting to see the progress we have made in SCLC! Many studies and clinical trials are underway to identify oncogenic drivers in SCLC. Once those drivers are known, researchers can then develop therapeutics to target those drivers.
One approach for improving our understanding of the molecular mechanisms of SCLC is to break the large disease into smaller segments that may be easier to target and treat. Researchers at the ASCO conference presented data showing that they are making progress identifying molecular subtypes of SCLC, such as SCLC-A, SCLC-N, SCLC-P, SCLC-I, and SCLC-Y. As researchers learn more about the molecular make-up of each subtype, they will be better equipped to develop effective, targeted treatments for SCLC.
Researchers are diving deep into these different SCLC subtypes by attempting to study the RNA molecules in individual SCLC cells to understand the differences and similarities between the subtypes. Already they have discovered that elevated levels of a protein called PLCG2 are likely to be associated with increased tumor metastasis and decreased patient survival. This detailed analysis of individual SCLC cells continues.
Scientists are also on the hunt for effective biomarkers for SCLC. One such biomarker, a protein called SLFN11, may be useful when predicting which SCLC patients will benefit from treatment with PARP inhibitors. A phase 2 clinical trial, called SWOG 1929, is currently accruing patients in order to study the efficacy of treating SLFN11-positive extensive-stage SCLC patients with a PARP inhibitor plus atezolizumab versus atezolizumab alone.
The impressive breadth and depth of lung cancer studies presented at the annual ASCO conference and the overall increase of therapeutic options for lung cancer patients is truly a testament to the hard work of physicians, scientists, patients, advocacy groups, medical staff, and policymakers. They have been working hard to save lives and improve patient outcomes during one of the most turbulent years in recent history. Many thanks to the frontline workers in the lung cancer community–we see you and we appreciate all that you do.
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Juhi Kunde, MA, is a science writer for LUNGevity.