Author: Daniel A. Saez, MSc, Manager of LungMATCH Navigation Program

Despite 2021 being another challenging year, we saw treatment options for lung cancer increase by leaps and bounds. In 2021 the treatment landscape for lung cancer evolved to provide breakthrough treatment options targeting mutations that were previously unavailable for patients. Additionally, new immunotherapy options were approved, giving more variety and treatment options as well as post-surgery options.

Targeted Therapy Approvals

In the targeted therapy space, there were five total approvals, three of which were for previously untargetable mutations. This means that before 2021, patients with these specific mutations targeted by the three drugs had no FDA approved options outside of chemotherapy and immunotherapy. The other two approvals opened up additional treatment options for patients who may have otherwise been limited.

New Drugs for New Targets

The three drugs targeting new mutations are Lumakras (sotorasib), Rybrevant (amivantamab-vmjw), and Exkivity (mobocertinib). Lumakras received approval for patients with non-small cell lung cancer (NSCLC) that has spread outside of the lungs and has the KRAS G12C mutation. Lumakras can only be received after a patient has tried at least one form of systemic treatment. The approval for Lumakras came from the CODEBREAK100 clinical trial which looked at objective response rates (the proportion of a patient’s tumor which shrinks) and duration of response. Due to the accelerated nature of the approval for Lumakras, more studies are ongoing for the drug to determine if patients could receive similar positive results from a lower dose. Other clinical trials are ongoing for more drugs targeting KRAS G12C and other KRAS mutations.

Rybrevant and Exkivity both received approval for patients with locally advanced or metastatic NSCLC that has the EGFR exon 20 insertion mutation. Both Rybrevant and Exkivity can only be received after a patient has tried at least one platinum doublet chemotherapy. Rybrevant received its approval based on the results of the CHRYSALIS trial which looked at overall response rate and how long the response lasted. Exkivity received its approval based on the results of the clinical trial Study101 which also evaluated overall response rate and duration of response.

New Drugs for Existing Targets

The two drugs approved in 2021 that target existing mutations are Tepmetko (tepotinib) and Lorbrena (lorlatinib). Tepmetko received approval for patients with NSCLC that has spread outside of the lungs and has a MET exon 14 skipping mutation. Prior to Tepmetko, the only drug available to these patients was Tabrecta (capmatinib). Lorbrena received approval for patients with NSCLC that has spread outside of the lungs and is ALK+. Prior to the approval of Lorbrena, patients relied on other drugs. Tepmetko’s approval came from the results of the VISION trial which evaluated overall response rate and duration of response. Due to the accelerated nature of Tepmetko’s approval, the FDA will continue to monitor and evaluate the clinical benefit of the treatment through confirmatory analysis. Lorbrena’s approval is based on the results of the StudyB7461006 clinical trial which compared the progression free survival of patients receiving Lorbrena compared to those taking a previously approved drug, Xalkori.

Immunotherapy Approvals

In 2021, one new immunotherapy drug received approval and one already approved drug received additional use for lung cancer patients. The newly approved drug is Libtayo (cemiplimab-rwlc) which is a PD-1 inhibitor. Libtayo received approval for first line treatment of patients with locally advanced or metastatic NSCLC that does not have other actionable mutations like EGFR and ALK and high PD-L1 expression. Libtayo represents another important option for patients who rely on immunotherapy. Libtayo’s approval comes from the results of the Study1624 clinical trial which evaluated overall survival and progression free survival of patients receiving Libtayo as compared to platinum based chemotherapy.

Tecentriq (atezolizumab) received an important addition to its FDA label in 2021, opening it as an option for patients than before. Tecentriq is now approved for patients who received surgery and chemotherapy after their surgery and have at least 1% PD-L1 expression. Tecentriq is the first immunotherapy approved for this adjuvant setting in early-stage NSCLC. Tecentriq’s new addition to FDA approved use is based on the results of the IMpower010 trial which compared the disease free survival of patients after surgery who received Tecentriq compared to those who only received best supportive care.

Small Cell Lung Cancer (SCLC) Approvals

While we didn’t see additional treatment approvals for SCLC in 2021, there was a therapy approval to help mitigate a side effect that many patients with SCLC experience from their chemotherapy called neutropenia or bone marrow suppression. Neutropenia makes it harder for patients to fight dangerous infections and can impact quality of life. The name of the newly approved drug is Cosela (trilaciclib) and it is the first drug to help patients experiencing this side effect. Cosela’s approval is based on the analysis of patients on three different clinical trials. The approval was guided by the proportion of patients who experienced severe neutropenia, and the duration of the neutropenia in patients who received Cosela before their chemotherapy compared to those who received a placebo.

There are still many drugs being studied in clinical trials that could be options for you or a loved one. If you would like to discuss any treatment or clinical trial options, please call our free HelpLine at 1-800-298-2436 and ask to speak to an expert LungMATCH navigator.