Lung Cancer (Part 2) 2021 

In May 2021, FDA approved amivantamab for EGFR exon 20 insertion mutation which occurs in adenocarcinoma non-smoker woman and bran metastasis . It produces 40% response rate. However it’s efficacy is not known for brain metastasis.

The US Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) in the adjuvant setting for patients with stage IB-IIIA non-small cell lung cancer (NSCLC) following resection and platinum-based chemotherapy. The FDA's decision was based on the results of the multicenter, triple-blind, randomized phase 3 KEYNOTE-091 trial, which demonstrated a significant improvement in disease-free survival (DFS). Researchers randomly assigned 1177 patients who had undergone complete resection to receive either pembrolizumab 200 mg or placebo intravenously every 3 weeks for up to 1 year. Patients had not received neoadjuvant radiotherapy or chemotherapy. Among the 1010 patients who received adjuvant platinum-based chemotherapy, the median DFS was 58.7 months in the pembrolizumab arm (n = 506) and 34.9 months in the placebo arm (hazard ratio, 0.73). In an exploratory subgroup analysis of the 167 patients who did not receive adjuvant chemotherapy, the DFS hazard ratio was 1.25. Overall survival data were not yet mature. Adverse reactions were largely similar to those observed in patients with NSCLC who receive pembrolizumab as a single agent. They included fatigue, pain, rash, diarrhea, pyrexia, constipation, and nausea. Adverse effects that were different included hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). Two patients experienced fatal myocarditis. The recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease recurrence, unacceptable toxicity, or up to 12 months of treatment.

The FDA granted approval to tremelimumab, in combination with durvalumab and platinum-based chemotherapy, for the treatment of patients with metastatic non-small cell lung cancer, according to a press release issued by the agency. The triplet was approved for patients whose cancers harbor no sensitizing EGFR mutations or ALK genomic tumor aberrations. The agency based its decision on results from the phase 3 POSEIDON study, which evaluated tremelimumab, durvalumab, and platinum-based chemotherapy in patients with metastatic NSCLC and no prior exposure to systemic therapy. Compared with patients assigned to 6 cycles of platinum-based chemotherapy alone, the tremelimumab-based combination resulted in a statistically significant improvement in overall survival (median, 14 months vs 11.7 months; HR = 0.77; 95% CI, 0.65-0.92; 2-sided P = .00304). Assignment to tremelimumab, durvalumab, and platinum-based chemotherapy was also associated with a significant improvement to progression-free survival (median, 6.2 months vs 4.8 months; HR = 0.72; 95% CI, 0.6-0.86; 2-sided P = .00031). Patients assigned to tremelimumab, durvalumab, and platinum-based chemotherapy achieved an overall response rate of 39% (95% CI, 34-44), compared with 24% (95% CI, 20-29) in patients assigned to platinum-based chemotherapy. The median durations of response were 9.5 months (95% CI, 7.2 to not reached) and 5.1 months (95% CI, 4.4-6), respectively. Treatment with tremelimumab was well tolerated. The most common adverse events included nausea, fatigue, decreased appetite, musculoskeletal pain, rash, and diarrhea. Grade 3 or grade 4 adverse events seen in at least 10% of the population included neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia, and thrombocytopenia. The FDA recommended that tremelimumab be given at an intravenous dose of 75 mg every 3 weeks in patients weighing 30 kg or more, with durvalumab administered at 1,500 mg and platinum-based chemotherapy. Treatment should continue for four cycles, followed by maintenance chemotherapy on a 4-week schedule. A fifth dose of tremelimumab should be given after 16 weeks.

The FDA recently gave regular approval to selpercatinib for the treatment of metastatic or locally advanced non-small cell lung cancer with a RET gene fusion, as well as the companion Oncomine Dx Target Test. Selpercatinib had previously received accelerated approval for advanced NSCLC in May of 2020. The federal agency based its accelerated approval on the multicenter, open-label LIBRETTO-001 trial, which consisted of 144 patients. For the regular approval, the FDA based its decision on the assessment of an additional 172 patients with 18 more months of follow-up. Patients were a median of 61 years old (range, 23-92). Patients were mostly female (58%), and approximately half (49%) were white, whereas 41% were Asian and 5% were Black. Nearly all patients (97%) had an ECOG status of 0 or 1, and 97% had metastatic cancer. Patients who had been previously treated had received a median of two prior therapies (range, 1-15), and more than half (58%) had been treated with anti-PD1/PD-L1 therapies. The main efficacy outcomes of the study were overall response rate and duration of response. In the 247 patients who had previously undergone platinum-based chemotherapy, the ORR was 61% (95% CI, 55-67), whereas the DOR was 28.6 months (95% CI, 20-not estimable). In the 69 patients who had not received prior therapy, the ORR was 84% (95% CI, 73-92), while the DOR was 20.2 months (95% CI, 13-not estimable). Headache, fatigue, constipation, nausea, abdominal pain, diarrhea, dry mouth, hypertension, edema, and rash were the most common side effects, all of which occurred in 25% or more of the patients. The recommended dose of selpercatinib is 120 mg twice a day by mouth in patients weighing less than 50 kg and 160 mg in those weighing more than 50 kg.

On November 10, 2022, the FDA approved tremelimumab in combination with durvalumab (Imfinzi, AstraZeneca Pharmaceuticals) and platinum-based chemotherapy for adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. Efficacy was evaluated in POSEIDON (NCT03164616), a randomized (1:1:1), multicenter, active-controlled, open-label study in patients with metastatic NSCLC who had not received prior systemic treatment. Patients were randomized to one of three treatment arms: (1) tremelimumab, durvalumab, and platinum-based chemotherapy for 4 cycles, followed by durvalumab and maintenance chemotherapy every 4 weeks. Patients were treated with a fifth tremelimumab dose at week 16; (2) durvalumab plus platinum-based chemotherapy for 4 cycles followed by durvalumab and maintenance chemotherapy; or (3) platinum-based chemotherapy for 6 cycles followed by maintenance chemotherapy. Treatment was continued until disease progression or unacceptable toxicity. This approval is based on a comparison of treatment arm 1 and 3 (675 patients). The major efficacy outcome measures were progression-free survival (PFS) assessed using blinded independent central review according to RECIST v1.1. and overall survival (OS). Tremelimumab plus durvalumab and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared to platinum-based chemotherapy (hazard ratio [HR] of 0.77 [95% CI: 0.65, 0.92], 2-sided p-value = 0.00304); median OS was 14 months (95% CI: 11.7, 16.1) and 11.7 months (95% CI: 10.5, 13.1) in the treatment arm 1 and 3, respectively. Median PFS was 6.2 months (95% CI: 5.0, 6.5) and 4.8 months (95% CI 4.6, 5.8) in the treatment arms, respectively (HR 0.72 [95% CI: 0.60, 0.86], 2-sided p-value = 0.00031). Overall response rate was 39% (95% CI: 34,44) and 24% (95% CI: 20, 29) in the treatment arm 1 and 3, respectively. Median duration of response was 9.5 months (95% CI: 7.2, not reached) and 5.1 months (95% CI: 4.4, 6.0) in the two treatment arms. The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue, decreased appetite, musculoskeletal pain, rash, and diarrhea. Grade 3 or 4 laboratory abnormalities (≥ 10%) were neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia, and thrombocytopenia. The recommended tremelimumab dose for patients weighing 30 kg or more is 75 mg IV every 3 weeks with durvalumab 1500 mg IV and platinum-based chemotherapy for 4 cycles, then durvalumab 1500 mg with maintenance chemotherapy every 4 weeks. A fifth tremelimumab dose (75 mg) should be given at week 16.

Cemiumab-rwlc (Lybtayo) was approved for advanced NSCLC. - On November 8, 2022, the Food and Drug Administration approved cemiplimab-rwlc (Libtayo, Regeneron Pharmaceuticals, Inc.) in combination with platinum-based chemotherapy for adult patients with advanced non-small cell lung cancer (NSCLC) with no EGFR, ALK, or ROS1 aberrations. Efficacy was evaluated in Study 16113 (NCT03409614), a randomized, multicenter, multinational, double-blind, active-controlled trial in 466 patients with advanced NSCLC who had not received prior systemic treatment. Patients were randomized (2:1) to either cemiplimab-rwlc plus platinum-based chemotherapy every 3 weeks for 4 cycles followed by cemiplimab-rwlc and maintenance chemotherapy or placebo plus platinum-based chemotherapy every 3 weeks for 4 cycles followed by placebo and maintenance chemotherapy. The main efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures were progression-free survival (PFS) and overall response rate (ORR) as assessed by blinded independent central review (BICR). Cemiplimab-rwlc plus platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared to placebo plus chemotherapy (hazard ratio [HR] of 0.71 [95% CI: 0.53, 0.93], two-sided p-value = 0.0140). Median OS was 21.9 months (95% CI: 15.5, not evaluable) in the cemiplimab-rwlc plus chemotherapy arm and 13.0 months (95% CI: 11.9, 16.1) in the placebo plus chemotherapy arm. Median PFS per BICR was 8.2 months (95% CI: 6.4, 9.3) in the cemiplimab-rwlc plus chemotherapy arm and 5.0 months (95% CI: 4.3, 6.2) in the placebo plus chemotherapy arm (HR 0.56; 95% CI: 0.44, 0.70, p

Osimertinib (Tagrisso) for up to 3 years after surgery and adjuvant chemotherapy prolongs DFS (OS data premature) if EGFR (+) in patients with stage II and IIIA.

The FDA has granted approval in 2021 to a CDK inhibitor, trilaciclib (Cosela) for the treatment of patients with extensive-stage small cell lung cancer (SCLC) to reduce chemotherapy-induced bone marrow suppression.

Nivolumab in combination with platinum doublet chemotherapy was approved by FDA in 3/2021 for neoadjuvant therapy for Non-Small Cell CA of the lung (CheckMate 816 ). indication is for adult patients with resectable NSCLC (tumors ≥ 4 cm or node positive: Stage IB, II, III). The recommended dosage is 360 mg in combination with platinum-doublet chemotherapy on the same day every 3 weeks for three cycles.,

On October 15, 2021, the Food and Drug Administration approved atezolizumab (Tecentriq, Genentech, Inc.) for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non-small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test. Atezolizumab is given for 1 year (q2,3 or 4 weeks). DFS benefit but OS data premature.

On October 15, 2021, the Food and Drug Administration approved atezolizumab (Tecentriq, Genentech, Inc.) for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non-small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test.

I would like to mention that patients with EGFR mutation or ALK rearrangement respond poorly to immunotherapy. And immunotherapy for those patients is contraindicated according to NCCN guideline. Those patients also have higher pulmonary toxicity with immunotherapy.

FDA approved trastuzumab deruxtecan (Enhertu) for untesectable or metastatic non-small cell lung cancer with (+) HER2 mutation. Enhertu is already approved for used in HER2-positive breast cancer and gastric cancer. Now it has become the first product approved by the US Food and Drug Administration (FDA) for use in HER2-positive lung cancer. About 3% of nonsquamous NSCLC tumors carry mutations in the HER2 gene, and they are associated with female sex, never-smokers, and a poor prognosis.

FDA in 2021also approved sotorasib (Lumakras) for KRAS G12C mutation which occurs in 13% of NSCLC. Response rate 38% with median duration of response 10 months.

In a randomized phase 2 study for recurrent metastatic non-small cell lung cancer, ramcirumab (Cyramza) + pembrilozumab (Keytruda) improved overall survival to 14.5 months, when compared with standard of care, ie, ramucirumab + paclitaxel (OS 11.6 months). However, progression free survival and overall response rate were the same between 2 groups. ascopubs.org/doi/full/10.1200/JCO.22.00912?bid=176070555&cid=DM10721

ASCO 2021 reported that atezolizumab with adjuvant chemotherapy improved DFS in PDL-1 (+) >1% NSCLC (stage II-IIIA or IB >4cm).

trastuzumab deruxtecan has shown to be effective for HER-2 (+) NSCLC producing 55% response rate with response duration about 9 months (NEJM 2021)

우와~ 교수님 건강하게 잘 지내시는거뵈니 너무 반갑습니다~ 림프종영상 잘보구 교수님 덕분에 힘내서 6차항암까지 잘 치료받구 결과기다리고 있습니다 림사랑에서 많은 환우,가족들에게 베풀어주신 사랑 잘 기억하고 교수님 귀한 조언따라 감사하며 힘닫는대로 베풀며 살도록 노력하겠습니다 환자들의 빛이신 김일철교수님 항상 건강하세요~^^

안녕하세요 교수님 항상 올려주시는 강의 감사히 보고 있습니다 한가지 여쭤 보고싶은게 있습니다 백혈병 혹은 림프종 환자가 동종조혈모세포이식 후 1~2년이 지나야 정상인 수준의 면역력이 된다고 들었는데 맞는가요? 혹시 그렇다면 동종이식 후 6개월 지나서 재발을 해서 항암치료를 받은 후 관해가 된다면 시간이 지남에 따라 새로자리 잡은 공여자 세포의 면역력으로 암세포 공격을 기대할 수 있을까요? 동종이식 후 이미 재발을 했다면 공여자 세포가 암세포를 공격 할 수 있는 희망은 없는건가요? 두서없는 질문 죄송합니다..

A MILLION APPRECIATION TO DR . ABDUL FOR CURED MY MUM CANCER.

안녕하세요 교수님 20살 된 아들의 병명은 T셀 급성모구성림프종 백혈병 이라는 진단을 받았네요 처음 코 안에 종양이 생기더니 몇칠사이로 입 목 사타구니 전신에 림프선 따라 혹이 만져졌어요 설상가상으로 골수까지 전이 되서 마지막 치료는 조혈모 세 포 이식 이라고 말씀해 주셨네요 급성으로 전이되는 병이라고 하더니 배 비장 침범해 복수도 차서 배도 점점 불러 오고 설사도 심해졌어요 물만 조금마셔도 바로 설사를 했네요 급하게 함암10월30일부터11윌1일까지 엔독산 3일 아드리인마이신 1일 함암 치료 하고 몸상태가 너무 안좋아 1싸이클대로 진행못 하고 빈크리스틴 은 못 했어요 신기하게 만져졌던 종양들이 모두 사라지고 몸 회복기를 같고 있던 중에 1주일이 지나자 바로 다시 목 양쪽으로 종양이 다시 만져졌어요 관해가 되지 않았다고 젊으니까 해보자고 하시며 2차 시타라빈 2틀동안 맞고 다시 감쪽 같이 종양들이 사라지더니 1주일후 다시 만져졌어요 오늘 주치의가 오셔서 더이상 치료는 힘들다고 함암이 들지를 안한다고 지켜보는 수밖에 없다는 말을 듣는 순간 너무나 마음이 아프고 아픈 모습을 지켜 볼수밖에 없다는 사실에 눈물만 나네요 몸 회복을 기다리는 순간에도 독한 T 림프종은 자라날것이고 교수님 전혀 방법이 없나 요 제발 답변좀 부탁드립니다

Sublobar resection is as good as lobectomy for early nonsmall cell lung cancer: size 2cm or smaller. www.nejm.org/doi/full/10.1056/NEJMoa2212083?query=featured_home